The #1 Longevity Community

Announcing Vitalist Bay, a Pop-Up City in the Bay Area

<p style="text-align: justify;">A unique project is set to go live next spring in the Bay Area. Organized by the Vitalism Foundation, it promises to be one of the largest longevity-related events ever.</p> <h2 style="text-align: justify;"><b>They’re popping up!</b></h2> <p style="text-align: justify;">Since the pop-up city of <a href="https://www.lifespan.io/news/zuzalu-shining-city-on-the-black-mountain/">Zuzalu</a> took the longevity community by storm in early 2023, its innovative concept has inspired a wave of adaptations around the globe. These include <a href="https://www.lifespan.io/news/vitalia-living-the-longevity-dream/">Vitalia</a> on the island of Roatan, Honduras; ZuVillage in Georgia (the country, not the state); and Zelar City in Berlin, each offering its own spin on the original formula.</p> <p style="text-align: justify;">A pop-up city gathers like-minded people, blending co-living with a packed schedule of activities such as conferences, workshops, and hackathons. When the project is longevity-focused, the daily routine revolves around health and wellness, including healthy meals, cold plunges, yoga classes, detailed blood tests, and on-site treatments.</p> <p><img fetchpriority="high" decoding="async" class="aligncenter size-full wp-image-134264" src="https://www.lifespan.io/wp-content/uploads/2024/12/Vitalism.png" alt="Vitalism" width="1000" height="552" srcset="https://www.lifespan.io/wp-content/uploads/2024/12/Vitalism.png 1000w, https://www.lifespan.io/wp-content/uploads/2024/12/Vitalism-400x221.png 400w, https://www.lifespan.io/wp-content/uploads/2024/12/Vitalism-717x396.png 717w, https://www.lifespan.io/wp-content/uploads/2024/12/Vitalism-256x141.png 256w, https://www.lifespan.io/wp-content/uploads/2024/12/Vitalism-300x166.png 300w, https://www.lifespan.io/wp-content/uploads/2024/12/Vitalism-150x83.png 150w, https://www.lifespan.io/wp-content/uploads/2024/12/Vitalism-480x265.png 480w, https://www.lifespan.io/wp-content/uploads/2024/12/Vitalism-600x331.png 600w, https://www.lifespan.io/wp-content/uploads/2024/12/Vitalism-360x199.png 360w, https://www.lifespan.io/wp-content/uploads/2024/12/Vitalism-262x145.png 262w, https://www.lifespan.io/wp-content/uploads/2024/12/Vitalism-555x306.png 555w" sizes="(max-width: 1000px) 100vw, 1000px" /></p> <p style="text-align: justify;">Pop-up cities give participants an inspiring glimpse into a future where people aren’t bound by national borders but instead unite around shared values and interests. This ambitious concept, known as “network states,” was coined by entrepreneur Balaji Srinivasan. Some projects, like Vitalia, have already taken the next step by establishing a continuous presence with a small, permanent community rather than disbanding after a few months.</p> <h2 style="text-align: justify;"><b>Betting big on the Bay Area</b></h2> <p style="text-align: justify;">Most pop-up cities have been set in remote or underdeveloped locations, due to factors like lower costs and relaxed regulations. Building such a project in a bustling, expensive metropolis is a serious challenge – one that Vitalist Bay is stepping up to meet.</p> <p style="text-align: justify;">Vitalist Bay, a future pop-up city set to operate in Berkeley, California, during April and May of 2025, is being organized by the Vitalism Foundation, a major non-profit in the longevity space. In a press release, the organizers described the initiative as “humanity’s boldest effort to extend healthy lifespan and solve aging” and “the Bay Area’s first longevity zone.”</p> <p style="text-align: justify;">Like a proper longevity-oriented pop-up city should, Vitalist Bay will offer its inhabitants and visitors perks like a gym, a sauna, a large co-working space, advanced diagnostics such as DEXA scans and VO2max tests, and, generally, a “pro-health social environment.” ‘Bayers’ will also be able to participate in a community clinical trial.</p> <h2 style="text-align: justify;"><b>The program</b></h2> <p style="text-align: justify;">Vitalist Bay boasts an exceptionally comprehensive program covering a variety of interconnected topics, including longevity science, decentralized science and network states, biostasis and cryopreservation, AI in biology, and investment in longevity biotech. Notably, an entire week will focus on healthcare policy, philosophy, and ethics – an encouraging sign of growing interest in longevity advocacy, a vital part of the movement.</p> <p style="text-align: justify;">“Aging and longevity have such wide scope – from policy and regulations to science and technology, investing in startups, and even crypto with decentralized science. Unfortunately, the interaction between these different areas has been quite limited,” Adam Gries, Vitalism’s co-founder, said to Lifespan.io. “Vitalist Bay is longevity’s new capital, which is a triple entendre – human capital, financial capital, and physical capital – because we feel longevity has been missing a focal point that converges its different aspects.”</p> <h2 style="text-align: justify;"><b>The locals and the visitors</b></h2> <p style="text-align: justify;">Despite the Bay Area’s notoriously high cost of living, Vitalist Bay will offer reasonably priced accommodations for several dozen permanent residents. “The event will be centered around the Lighthaven campus, where the rationalist community is based,” said Nathan Cheng, co-founder of Vitalism and the Longevity Biotech Fellowship. “We’ll bring in hundreds, if not thousands, of longevity experts across different domains with the common focus of solving the problem of aging.”</p> <p style="text-align: justify;">The primary emphasis, however, will be on visitors. “Vitalia and Zuzalu were designed as pop-up cities with residents as the dominant group,” Adam noted. “Our longevity zone is different – the dominant group will be visitors coming for shorter periods. With a venue that can host a thousand people but only 70 residents, we’re expecting thousands of attendees to participate in our conferences.”</p> <p style="text-align: justify;">Elaborating on why Vitalist Bay differs from its predecessors, Adam added, “Being in the Bay Area is crucial. Long-term pop-up cities in remote locations with limited infrastructure, research ecosystems, or innovation history are inherently restrictive. Think about the 10,000 or more angel investors in the Bay Area; how many would travel to Vitalia? Maybe the hardcore enthusiasts, but not those who are merely curious or geographically tied. With a local event, we can spark engagement beyond the dedicated longevity community.”</p> <h2 style="text-align: justify;"><b>What’s next?</b></h2> <p style="text-align: justify;">“Among the outputs we’re aiming for,” Nathan said, “are policy and ethics statements from philosopher groups, think tanks with recommendations for research funding priorities, and local community partnerships that emphasize the pro-social aspects of longevity. We also want to engage with the local art scene and, more broadly, build projects that bridge different parts of the longevity ecosystem. Of course, we’ll try to get more capital into companies and initiatives, both for-profit and nonprofit.”</p> <p style="text-align: justify;">Another ambitious goal is to create a longer-term physical presence in the Bay Area. “For that,” Nathan explained, “we’re partnering with Berlin House, which owns a 16-story tower in San Francisco. We’ll be governing one floor dedicated to longevity in partnership with VitaDAO and Foresight Institute. This could become our longer-term venue after the two-month event.”</p> <div class="textwidget"><div class="sep-2"></div> <div class="life-highlight-box lhbox-has-zoom-yes l-hbox-size-large l-hbox-edges-square" style="background-color: #cef0f5;"><div class="l-hbox-lower"><div class="l-hbox-lower-desc" style="color:#000;">We would like to ask you a small favor. <strong>We are a non-profit foundation</strong>, and unlike some other organizations, we have no shareholders and no products to sell you. <strong>All our news and educational content is free</strong> for everyone to read, but it does mean that we rely on the help of people like you. Every contribution, no matter if it’s big or small, <strong>supports independent journalism</strong> and sustains our future. </div><style>.rb--e3f4f564d13aa10 a {background-color:#1e4fba;}.rb--e3f4f564d13aa10 a:hover {background-color:#79bcf0;}</style><div class="l-hbox-lower-cta rb--e3f4f564d13aa10"><a href="https://www.lifespan.io/how-you-can-help/" target="_self" rel="noopener">Yes I will donate❤️</a></div></div></div> </div> <div id="playht-shortcode" data-shortcode=" <div id="playht-iframe-wrapper" style="display:flex; max-height:"90px"; justify-content:center"> <iframe allowfullscreen="" frameborder="0" scrolling="no" class="playht-iframe-player" data-appId="E9FaMfn-qe" article-url="https://www.lifespan.io/?p=134247" data-voice="en-US-BrandonNeural" src="https://play.ht/embed/?article_url=https://www.lifespan.io/?p=134247&voice=en-US-BrandonNeural&config={"width":""100%"","height":""90px"","alignment":"center","title":"Audio","message":"Hello","download_text_button":"Download"}" width=""100%"" height=""90px"" style="max-height:"90px""> </iframe> </div>"></div>

BioAge Labs Ends STRIDES Phase 2 Clinical Trial

These statements involve risks and uncertainties that could cause actual results to differ materially from those reflected in such statements, including: our ability to develop, obtain regulatory approval for and commercialize our product candidates; the timing and results of preclinical studies and clinical trials; the risk that positive results in a preclinical study or clinical trial may not be replicated in subsequent trials or success in early stage clinical trials may not be predictive of

Longevity Market Recap – November 2024

<p style="text-align: justify;">As we head toward the festive season, ‘sharing is caring’ really is the motto in the longevity world. Collaborations between companies, foundations, and funders are seeing early results.</p> <p style="text-align: justify;">From AI discoveries to potential policy changes that allow wider medicine access, November has been a month of growth. Of course, not all ambitious adventures succeed, but transformative change in longevity tech is making strides.</p> <h2 style="text-align: justify;">Upcoming conferences and events</h2> <h3 style="text-align: justify;"><b>2nd Roundtable of Longevity Clinics is underway</b></h3> <p style="text-align: justify;">On December 6-7 2024, the International Institute of Longevity will host the 2nd Roundtable of Longevity Clinics. This event brings together leading longevity practitioners, businesses, and investors in one space to delve into epigenetic clocks, regenerative medicine, clinical interventions, and lifestyle practices such as nutrition and exercise, with a focus on enhancing human healthspan and lifespan. Find out more about the event<a href="https://iiol.eu/"> here</a>.</p> <h3 style="text-align: justify;"><b>Founders Longevity Forum in Singapore is set for February</b></h3> <p style="text-align: justify;">The Founders Longevity Forum will gather experts in epigenetics, AI, and regenerative medicine from around the world. The recently released agenda includes precision geromedicine and longevity investment as topics of interest, focusing on healthspan extension and aging solutions. Speakers include Hannah Went and Petr Sramek. Tickets to the event are available<a href="https://eventregistration.ff.co/founderslongevityforumsingapore/7266971"> here</a>.</p> <h2 style="text-align: justify;"><strong>Tech breakthroughs & new research</strong></h2> <h3 style="text-align: justify;"><b>Genesis Therapeutics partners with NVIDIA to accelerate AI drug discovery</b></h3> <p style="text-align: justify;">AI-focused drug discovery company<a href="https://genesistherapeutics.ai/"> Genesis Therapeutics</a> has announced a partnership with NVIDIA to optimize its neural networks and enhance its process for finding 3D protein and molecule data. This partnership focuses on refining neural networks and using generative and predictive Ai to target proteins and design therapies.</p> <h3 style="text-align: justify;"><b>Telomir Pharma moving ahead to Phase 2 after successful clinical trial</b></h3> <p style="text-align: justify;">Telomere-focused biotech company<a href="https://telomirpharma.com/"> Telomir Pharmaceuticals</a> has announced its plans to proceed to Phase 2 clinical trials with its compound Telomir-1. In recent <i>C. elegans</i> studies, the drug has provided improvements in lifespan, healthspan, and mobility, making it a leading candidate for future testing.</p> <h3 style="text-align: justify;"><b>Virtual reality tech aids in early cognitive decline detection</b></h3> <p style="text-align: justify;"><a href="https://virtuleap.com/">Virtuleap</a>, a VR company that combines neuroscience with technology, has created a tool alongside pharmaceutical companies to enhance early detection of dementia. The current kit, known as Cogniclear VR analyses real-world tasks and physiological cues like pupil dilation and heart rate variability to gather 250K+ data points in just under 3 minutes. This new system could offer clinicians a new way to analyze cognitive health and aid in early interventions.</p> <h2 style="text-align: justify;"><strong>DeSci and DAOs</strong></h2> <h3 style="text-align: justify;"><b>VitaDAO has partnered with Pump Science to test longevity compounds</b></h3> <p style="text-align: justify;">VitaFAST, backed by VitaDAO, has teamed up with Pump Science to utilize gamification to test new longevity compounds. The project seeks to evaluate compounds over 12 weeks in worm life extension experiments. During this initial stage, any promising compounds will progress to further testing, being incorporated into VitaFAST’s research and products.</p> <h3 style="text-align: justify;"><b>Crypto platform backs BIO Protocol to boost science funding</b></h3> <p style="text-align: justify;">Binance Labs has announced its backing of BIO Protocol, a decentralized science platform that utilizes blockchain to fund biotech DAOs working in research for longevity, rare disease and other areas. Dubbed the “Y Combinator”, a start-up accelerator, of science, BIO has raised $13 million to date and has plans to keep expanding.</p> <h2 style="text-align: justify;"><strong>News and funding</strong></h2> <h3 style="text-align: justify;"><b>$84M secured by TRex Bio to advance immune-regulating therapy</b></h3> <p style="text-align: justify;">San Francisco-based biotech<a href="https://trex.bio/"> TRex Bio</a> has just raised $84 million in Series B funding to support its Phase 1 trial of TRB-061, a TNFR2 agonist targeting regulatory T cells (Tregs). This is hoped to control inflammation and promote healing. Led by Delos Capital, the funding will also support plans to expand the company’s clinical pipelines for wider therapies into inflammatory and autoimmune diseases.</p> <h3 style="text-align: justify;"><b>Metabolic tracking on your finger: coming soon</b></h3> <p style="text-align: justify;"><a href="https://www.dexcom.com/en-IE">Dexcom</a> and<a href="https://ouraring.com/"> Oura</a> have partnered to reinvigorate the health wearables market with innovative ring technology that allows users to monitor their blood glucose level from a ring. Dexcom is a leader in the glucose monitoring sphere, whole Oura is known for its health wearables that track metrics such as sleep, stress, health and more. This latest collaboration has seen Dexcom invest $75 million into Oura with plans for a launch in mid 2025.</p> <h3 style="text-align: justify;"><b>Potential Medicare expansion could offer obesity drugs to more people</b></h3> <p style="text-align: justify;">Weight loss drugs, such as Wegovy, Mounjaro, Saxenda, and Ozempic, have hit headlines recently. As these drugs are currently available in both the US and UK as treatments for diabetes, Medicare in the US is contemplating offering increased access to these preparations to a wider range of the population. The latest discussion suggests that offering these medications to obese patients could cut out-of-pocket expenses by 95% and reduce diabetes risk more broadly. Changes to these regulations could be set to appear as early as 2026.</p> <h3 style="text-align: justify;"><b>AI doctor’s office shuts</b></h3> <p style="text-align: justify;">Not all innovations end with success, but they are always learning experiences. An AI health start-up, which last year raised $500 million to create the world’s first AI doctor’s office, known as a CarePod, has ceased its operations. As the team at Forward helps its patients look for new providers, new lessons are learned for the future of AI in healthcare.</p> <h2 style="text-align: justify;">Social media pages to follow this month</h2> <p style="text-align: justify;"><a href="https://twitter.com/bioprotocol">BIO Protocol</a> — DeSci accelerator</p> <p style="text-align: justify;"><a href="https://twitter.com/paulkhls">Paul Kohlhaas</a> — Pioneer in the world of DeSci</p> <p style="text-align: justify;"><a href="https://twitter.com/QuantumBioDAO">Quantum Bio DAO</a> — Supports community building, governance tokens, and open competition for research grants</p> <div id="playht-shortcode" data-shortcode=" <div id="playht-iframe-wrapper" style="display:flex; max-height:"90px"; justify-content:center"> <iframe allowfullscreen="" frameborder="0" scrolling="no" class="playht-iframe-player" data-appId="E9FaMfn-qe" article-url="https://www.lifespan.io/?p=134195" data-voice="en-US-JennyNeural" src="https://play.ht/embed/?article_url=https://www.lifespan.io/?p=134195&voice=en-US-JennyNeural&config={"width":""100%"","height":""90px"","alignment":"center","title":"Audio","message":"Hello","download_text_button":"Download"}" width=""100%"" height=""90px"" style="max-height:"90px""> </iframe> </div>"></div>

Nuclear Expression of a Mitochondrial Gene in Mice

<p style="text-align: justify;">Scientists from the Longevity Research Institute (LRI), which was formed by the merger of SENS Research Foundation and Lifespan.io, have achieved <a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC8681429/">expression of an essential mitochondrial gene in the nucleus</a> and proper functioning of the protein. This could pave the way for curing diseases caused by mitochondrial mutations [1].</p> <h2 style="text-align: justify;"><b>The fragile mitochondrial DNA</b></h2> <p style="text-align: justify;">The prevailing scientific consensus is that mitochondria were once independent microorganisms that entered a symbiotic relationship with larger cells. This duo gave rise to eukaryotic cells: the building blocks of all multicellular life. Without that fateful “marriage,” complex life would not exist, as mitochondria provide cells with essential energy via oxidative phosphorylation.</p> <p style="text-align: justify;">Over the millennia, mitochondria have retained their own DNA. However, this mitochondrial DNA (mtDNA) has several vulnerabilities: it lacks the protective proteins that nuclear DNA is wrapped around (histones), has fewer repair mechanisms compared to nuclear DNA, and exists in a harsh environment of oxidative stress generated by its own metabolic activity.</p> <p style="text-align: justify;">The fragility of mtDNA might have contributed to the relocation of most of its genes to nuclear DNA. Proteins encoded by those genes are synthesized in the cytosol and transported across the cell into mitochondria via a highly regulated process. However, 13 essential proteins involved in oxidative phosphorylation remain encoded by mtDNA and still suffer from the same vulnerabilities. This makes mtDNA prone to mutations, particularly as we age.</p> <p style="text-align: justify;">Mutations in mtDNA contribute to a range of diseases, such as Leber hereditary optic neuropathy (LHON), and are linked to a wide range of age-related pathologies, including sarcopenia and Alzheimer’s disease [2]. Addressing problems caused by mtDNA mutations is a major challenge in biomedical research. However, in this study, LRI researchers have achieved a significant breakthrough by successfully relocating a mitochondrial gene to the nucleus in vivo.</p> <h2 style="text-align: justify;"><b>Overcoming the challenges</b></h2> <p style="text-align: justify;">Previously, the same team had achieved promising results in vitro [3], but finding a suitable animal model proved difficult: mtDNA genes are so essential that mutations in them usually render mice non-viable. However, a particular strand of mice exists that harbors a relatively benign mutation in ATP8, a gene encoding a subunit of the ATP synthase complex, which causes only a mildly pathologic phenotype. Alongside those mutants, wild-type mice were used as controls.</p> <p style="text-align: justify;">The team synthesized a nuclear-compatible version of ATP8 and inserted it into the ROSA26 locus, a well-characterized “safe harbor” site in the mouse genome. This locus is widely used in genetic engineering because it allows stable organism-wide expression of inserted genes without interfering with other essential genomic functions.</p> <p style="text-align: justify;">The researchers had to overcome significant technical challenges to achieve nuclear expression of a gene that is normally expressed in mitochondria (allotopic expression) and to make the protein transferrable to mitochondria. For instance, they found that efficient allotopic expression requires codon optimization: altering the DNA sequence of a gene using codons that are more efficiently translated by ribosomes.</p> <h2 style="text-align: justify;"><b>Efficient, persistent, non-immunogenic</b></h2> <p style="text-align: justify;">Eventually, their efforts paid off: allotopic ATP8 was able to compete with mitochondrial ATP8 even in wild-type mice and outperformed the mutant ATP8. The allotopic gene was expressed in all the tissues that the researchers tested, and the protein successfully integrated into the mitochondrial machinery.</p> <p style="text-align: justify;">“The key question was ‘How well can an allotopic protein compete with pre-existing protein?’” said Dr. Amutha Boominathan, Assistant Professor and Principal Investigator at LRI and the study’s leading author. “One fundamental concept in the field is that mitochondrial DNA exists because proteins need to be synthesized on demand for easier incorporation into their respective complexes.”</p> <p style="text-align: justify;">“For allotopic expression to succeed,” she explained, “you must demonstrate that protein coming from the nuclear side can be incorporated with similar efficiency. In wild-type mice, we see equal efficiency between endogenous and exogenous proteins. In our mutant model, we see increasing incorporation over time, suggesting the nuclear protein actually outcompetes the mutated one from a stability perspective.”</p> <p style="text-align: justify;">Importantly, the allotopic gene functioned well in the genetically modified mice’s offspring for at least four generations, with no adverse effects on fertility. While mtDNA can sometimes trigger an immune reaction when released into the cytoplasm, this gene was also well-tolerated by the immune system, as confirmed by cytokine array analysis.</p> <p><img fetchpriority="high" decoding="async" class="aligncenter size-full wp-image-134189" src="https://www.lifespan.io/wp-content/uploads/2024/12/Nuclear-mtDNA.png" alt="Nuclear mtDNA" width="996" height="996" srcset="https://www.lifespan.io/wp-content/uploads/2024/12/Nuclear-mtDNA.png 996w, https://www.lifespan.io/wp-content/uploads/2024/12/Nuclear-mtDNA-400x400.png 400w, https://www.lifespan.io/wp-content/uploads/2024/12/Nuclear-mtDNA-396x396.png 396w, https://www.lifespan.io/wp-content/uploads/2024/12/Nuclear-mtDNA-256x256.png 256w, https://www.lifespan.io/wp-content/uploads/2024/12/Nuclear-mtDNA-300x300.png 300w, https://www.lifespan.io/wp-content/uploads/2024/12/Nuclear-mtDNA-150x150.png 150w, https://www.lifespan.io/wp-content/uploads/2024/12/Nuclear-mtDNA-480x480.png 480w, https://www.lifespan.io/wp-content/uploads/2024/12/Nuclear-mtDNA-600x600.png 600w, https://www.lifespan.io/wp-content/uploads/2024/12/Nuclear-mtDNA-360x360.png 360w, https://www.lifespan.io/wp-content/uploads/2024/12/Nuclear-mtDNA-262x262.png 262w, https://www.lifespan.io/wp-content/uploads/2024/12/Nuclear-mtDNA-555x555.png 555w, https://www.lifespan.io/wp-content/uploads/2024/12/Nuclear-mtDNA-45x45.png 45w" sizes="(max-width: 996px) 100vw, 996px" /></p> <h2 style="text-align: justify;"><b>A blueprint for the future</b></h2> <p style="text-align: justify;">In the paper, the researchers note that their successful proof of concept does not necessarily apply to all mtDNA genes, and many challenges lie ahead. However, Boominathan is optimistic: “This provides a platform for testing other genes. With appropriate engineering we can overcome all the challenges. We’ve proven it for one protein and have promising data for others. What we’ve demonstrated here is the feasibility of expressing mitochondrial genes in a whole-body context. The inheritance patterns and lack of immune response are particularly encouraging for therapeutic applications.”</p> <p style="text-align: justify;">There are over 250 mitochondrial DNA diseases that could potentially benefit from this approach, according to Boominathan. “If we can achieve allotopic expression for all 13 genes,” she said, “we’d have a pathway to treat many of these rare diseases.”</p> <h2 style="text-align: justify;"><b>The aging connection</b></h2> <p style="text-align: justify;">LHON, one of the diseases that the researchers are after, “is actually an aging disorder,” Boominathan explained. “While the mutation is inherited, it specifically affects males over 40. These mutations amplify with age, particularly in tissues with high oxidative phosphorylation demands, like retinal ganglion cells. Symptoms only appear when the mutation load reaches a certain threshold.”</p> <p style="text-align: justify;">This is particularly relevant to post-mitotic cells that form the brain, skeletal muscle, and cardiac tissue since those cells cannot dilute mutations through cell division. “While internal recycling mechanisms like mitophagy exist, they decline with age,” said Boominathan. “If you inherit a mutation or acquire one early in life, it amplifies over time as mitophagy decreases, and these mutations often have an advantage that helps them take over.”</p> <h2 style="text-align: justify;"><b>A three-pronged approach</b></h2> <p style="text-align: justify;">“This work represents the culmination of more than a decade’s worth of effort to provide a genetic backup system for mitochondrial DNA in mammals, for which inherited mutations cause disease in nearly 1 in 200 people,” said Dr. E. Lillian Fishman, Director of Research and Education at LRI, about the study. “I am proud of Dr. Boominathan and her team’s persistence to rise to meet this technically challenging proof-of-concept that paves the way for the treatment of debilitating mitochondrial diseases like Leigh’s syndrome and progressive diseases of aging.”</p> <p style="text-align: justify;">This study was done as part of MitoSENS, a wider LRI project that includes a three-pronged approach to mitochondrial dysfunction. In addition to allogenic mtDNA expression, the researchers pursue boosting mitophagy with small molecules and de novo synthesis of healthy mtDNA for transfer into exogenous mitochondria, followed by introduction into cells.</p> <div class="textwidget"><div class="sep-2"></div> <div class="life-highlight-box lhbox-has-zoom-yes l-hbox-size-large l-hbox-edges-square" style="background-color: #cef0f5;"><div class="l-hbox-lower"><div class="l-hbox-lower-desc" style="color:#000;">We would like to ask you a small favor. <strong>We are a non-profit foundation</strong>, and unlike some other organizations, we have no shareholders and no products to sell you. <strong>All our news and educational content is free</strong> for everyone to read, but it does mean that we rely on the help of people like you. Every contribution, no matter if it’s big or small, <strong>supports independent journalism</strong> and sustains our future. </div><style>.rb--a7d260c17453c8 a {background-color:#1e4fba;}.rb--a7d260c17453c8 a:hover {background-color:#79bcf0;}</style><div class="l-hbox-lower-cta rb--a7d260c17453c8"><a href="https://www.lifespan.io/how-you-can-help/" target="_self" rel="noopener">Yes I will donate❤️</a></div></div></div> </div> <h2 style="text-align: justify;"><b>Literature</b></h2> <p style="text-align: justify;">[1] Begelman, D. V., Dixit, B., Truong, C., King, C. D., Watson, M. A., Schilling, B., … & Boominathan, A. (2024). Exogenous Expression of ATP8, a Mitochondrial Encoded Protein, From the Nucleus In Vivo. Molecular Therapy Methods & Clinical Development.</p> <p style="text-align: justify;">[2] Zhunina, O. A., Yabbarov, N. G., Grechko, A. V., Yet, S. F., Sobenin, I. A., & Orekhov, A. N. (2020). Neurodegenerative diseases associated with mitochondrial DNA mutations. Current Pharmaceutical Design, 26(1), 103-109.</p> <p style="text-align: justify;">[3] Boominathan, A., Vanhoozer, S., Basisty, N., Powers, K., Crampton, A. L., Wang, X., … & O’Connor, M. S. (2016). Stable nuclear expression of ATP8 and ATP6 genes rescues a mtDNA Complex V null mutant. Nucleic acids research, 44(19), 9342-9357.</p> <div id="playht-shortcode" data-shortcode=" <div id="playht-iframe-wrapper" style="display:flex; max-height:"90px"; justify-content:center"> <iframe allowfullscreen="" frameborder="0" scrolling="no" class="playht-iframe-player" data-appId="E9FaMfn-qe" article-url="https://www.lifespan.io/?p=134185" data-voice="en-US-BrandonNeural" src="https://play.ht/embed/?article_url=https://www.lifespan.io/?p=134185&voice=en-US-BrandonNeural&config={"width":""100%"","height":""90px"","alignment":"center","title":"Audio","message":"Hello","download_text_button":"Download"}" width=""100%"" height=""90px"" style="max-height:"90px""> </iframe> </div>"></div>

Fragmented Mitochondria Linked to Muscle Weakness

<p style="text-align: justify;">In a study published in <i>Aging Cell</i>, researchers have outlined <a href="https://onlinelibrary.wiley.com/doi/full/10.1111/acel.14386">a relationship between mitochondrial fragmentation in skeletal muscle and the loss of strength with age</a>.</p> <h2 style="text-align: justify;"><b>Broken power plants</b></h2> <p style="text-align: justify;"><div class="wpv-grid grid-1-1 wpv-first-level unextended animation-from-left"><div class="topic-box-item" style="background-color:#fff"><a href="https://www.lifespan.io/topic/mitochondrial-dysfunction/" class="topic-thumb-link"><div class="topic-box-thumb-wrap topic-thumb-align-left"><div class="topic-box-thumb" style="background:url(https://www.lifespan.io/wp-content/uploads/2021/04/Mitochondrion.jpg) no-repeat center center;background-size: contain;"><img fetchpriority="high" decoding="async" width="1000" height="562" src="https://www.lifespan.io/wp-content/uploads/2021/04/Mitochondrion.jpg" class="attachment-full size-full wp-post-image" alt="Mitochondrion" srcset="https://www.lifespan.io/wp-content/uploads/2021/04/Mitochondrion.jpg 1000w, https://www.lifespan.io/wp-content/uploads/2021/04/Mitochondrion-400x225.jpg 400w, https://www.lifespan.io/wp-content/uploads/2021/04/Mitochondrion-705x396.jpg 705w, https://www.lifespan.io/wp-content/uploads/2021/04/Mitochondrion-256x144.jpg 256w, https://www.lifespan.io/wp-content/uploads/2021/04/Mitochondrion-300x169.jpg 300w, https://www.lifespan.io/wp-content/uploads/2021/04/Mitochondrion-150x84.jpg 150w, https://www.lifespan.io/wp-content/uploads/2021/04/Mitochondrion-480x270.jpg 480w, https://www.lifespan.io/wp-content/uploads/2021/04/Mitochondrion-600x337.jpg 600w, https://www.lifespan.io/wp-content/uploads/2021/04/Mitochondrion-360x202.jpg 360w, https://www.lifespan.io/wp-content/uploads/2021/04/Mitochondrion-262x147.jpg 262w, https://www.lifespan.io/wp-content/uploads/2021/04/Mitochondrion-555x312.jpg 555w" sizes="(max-width: 1000px) 100vw, 1000px" /></div></div></a><a class="topic-info-link" href="https://www.lifespan.io/topic/mitochondrial-dysfunction/"><div class="topic-box-title">Why We Age: Mitochondrial Dysfunction</div><div class="topic-box-desc">As they age, the mitochondria in our cells lose their ability to provide cellular energy and release reactive oxygen species that harm cells and cause increasing levels of systemic inflammation.<br><span class="topi-read-more">Read More</span></div></a></div></div></p> <p style="text-align: justify;">As its authors point out, this is far from the first study to link mitochondrial dysfunction and aging in muscle [1], nor is it the first to connect exercise habits, aging, mitochondria, and the loss of physical function [2].</p> <p style="text-align: justify;">There has also been significant prior work showing how the mitochondria in muscle tissue behave. Mitochondria in muscle are not equal in their behaviors: the mitochondria closest to the blood-filled capillaries (subsarcolemmal mitochondria) bring energy to more centrally located ones (intermyofibrillar mitochondria) through an intracellular network [3]. Fragmentation of this network destroys this energy transfer but may also offer protection against damage being transferred as well [4].</p> <p style="text-align: justify;">Too much fragmentation and fission, however, causes muscle wasting in mice [5]; the opposite, mitochondrial fusion, causes muscles to grow in these animals [6]. The researchers’ previous work on healthy volunteers demonstrated that fragmentation begins to occur at day 6 of bed rest, while functional impairments were found to occur on day 55 [7]. However, that work did not prove one way or another whether mitochondrial fragmentation is a useful biomarker or warning sign for age-related muscle decline.</p> <h2 style="text-align: justify;"><b>Decline begins before retirement</b></h2> <p style="text-align: justify;">Wanting to avoid physical inactivity as a confounder and suspecting that this process may not be the same as actual sarcopenia, the researchers recruited a dozen young (average age 27) and ten middle-aged (average age 55) volunteers rather than significantly older people. The older group was slightly more overweight than the younger group.</p> <p style="text-align: justify;">Unsurprisingly, the younger people’s muscles used more oxygen to generate more power than the older people’s, according to multiple metrics of respiration and energy use. This was not linked to blood flow; instead, it was linked to how the muscles pull oxygen from the blood.</p> <p style="text-align: justify;">The researchers then examined the mitochondria more closely in biopsied muscle tissue. The total density of the intermyofibrillar mitochondria was the same between younger and older people; however, the older people had more, smaller mitochondria. While their shapes did not differ, markers of mitochondrial fragmentation were greater in this area in the older group.</p> <p style="text-align: justify;">In the subsarcolemmal area, however, the older people had approximately as many mitochondria as the younger people, which led to a reduction of density with age as these mitochondria were also smaller. Here, too, they were found to be significantly more fragmented. This fragmentation in both areas was associated with the accumulation of fat (lipid) droplets.</p> <h2 style="text-align: justify;"><b>Looking ever closer</b></h2> <p style="text-align: justify;">There were also differences involving the tiny folds inside mitochondria (cristae). Younger people’s mitochondria had regular and dense cristae, while those of older people were less regular, with some areas having no cristae at all. This, the researchers hold, represents “age-associated deterioration at the level of the individual mitochondrion.” Interestingly, however, further data suggests that the increased number of smaller mitochondria may have made up for this, restoring some of the lost function.</p> <p style="text-align: justify;">The authors then pivoted to the key thrust of their research: the connection between fragmentation and loss of capacity. Fragmentation in the intermyofibrillar mitochondria and a reduction in the cristae was found to be responsible for nearly all of the changes in the well-known metric of VO2max. Unsurprisingly, the density of the subsarcolemmal mitochondria was found to be associated with the muscles’ ability to extract oxygen from blood.</p> <p style="text-align: justify;">The researchers believe that their findings explain the basic reasons why people lose strength with age, even in the absence of defined sarcopenia. They also warn that this mitochondrial dysfunction only gets worse with aging. Furthermore, they hold that their findings “reflect an early ageing phenotype, making the mitochondrial changes observed herein strong candidates for intervention studies aiming to slow the progression of the effects of ageing on physical function.”</p> <p style="text-align: justify;">As exercise is associated with mitochondrial fusion [8] and one study had suggested that six months of endurance training can compensate for 30 years of aging [9], the authors suggest that further research on exercise in older people should be done with a close examination into mitochondrial changes.</p> <div class="textwidget"><div class="sep-2"></div> <div class="life-highlight-box lhbox-has-zoom-yes l-hbox-size-large l-hbox-edges-square" style="background-color: #cef0f5;"><div class="l-hbox-lower"><div class="l-hbox-lower-desc" style="color:#000;">We would like to ask you a small favor. <strong>We are a non-profit foundation</strong>, and unlike some other organizations, we have no shareholders and no products to sell you. <strong>All our news and educational content is free</strong> for everyone to read, but it does mean that we rely on the help of people like you. Every contribution, no matter if it’s big or small, <strong>supports independent journalism</strong> and sustains our future. </div><style>.rb--b05315fb528962 a {background-color:#1e4fba;}.rb--b05315fb528962 a:hover {background-color:#79bcf0;}</style><div class="l-hbox-lower-cta rb--b05315fb528962"><a href="https://www.lifespan.io/how-you-can-help/" target="_self" rel="noopener">Yes I will donate❤️</a></div></div></div> </div> <h2 style="text-align: justify;"><b>Literature</b></h2> <p style="text-align: justify;">[1] Gouspillou, G., Bourdel‐Marchasson, I., Rouland, R., Calmettes, G., Biran, M., Deschodt‐Arsac, V., … & Diolez, P. (2014). Mitochondrial energetics is impaired in vivo in aged skeletal muscle. <i>Aging cell</i>, <i>13</i>(1), 39-48.</p> <p style="text-align: justify;">[2] Grevendonk, L., Connell, N. J., McCrum, C., Fealy, C. E., Bilet, L., Bruls, Y. M., … & Hoeks, J. (2021). Impact of aging and exercise on skeletal muscle mitochondrial capacity, energy metabolism, and physical function. <i>Nature communications</i>, <i>12</i>(1), 4773.</p> <p style="text-align: justify;">[3] Glancy, B., Hartnell, L. M., Malide, D., Yu, Z. X., Combs, C. A., Connelly, P. S., … & Balaban, R. S. (2015). Mitochondrial reticulum for cellular energy distribution in muscle. <i>Nature</i>, <i>523</i>(7562), 617-620.</p> <p style="text-align: justify;">[4] Glancy, B., Hartnell, L. M., Combs, C. A., Femnou, A., Sun, J., Murphy, E., … & Balaban, R. S. (2017). Power grid protection of the muscle mitochondrial reticulum. <i>Cell reports</i>, <i>19</i>(3), 487-496.</p> <p style="text-align: justify;">[5] Romanello, V., Guadagnin, E., Gomes, L., Roder, I., Sandri, C., Petersen, Y., … & Sandri, M. (2010). Mitochondrial fission and remodelling contributes to muscle atrophy. The EMBO journal, 29(10), 1774-1785.</p> <p style="text-align: justify;">[6] Cefis, M., Dargegen, M., Marcangeli, V., Taherkhani, S., Dulac, M., Leduc‐Gaudet, J. P., … & Gouspillou, G. (2024). MFN2 overexpression in skeletal muscles of young and old mice causes a mild hypertrophy without altering mitochondrial respiration and H2O2 emission. Acta Physiologica, 240(5), e14119.</p> <p style="text-align: justify;">[7] Eggelbusch, M., Charlton, B. T., Bosutti, A., Ganse, B., Giakoumaki, I., Grootemaat, A. E., … & Wüst, R. C. (2024). The impact of bed rest on human skeletal muscle metabolism. <i>Cell Reports Medicine</i>, <i>5</i>(1).</p> <p style="text-align: justify;">[8] Huertas, J. R., Ruiz‐Ojeda, F. J., Plaza‐Díaz, J., Nordsborg, N. B., Martín‐Albo, J., Rueda‐Robles, A., & Casuso, R. A. (2019). Human muscular mitochondrial fusion in athletes during exercise. <i>The FASEB Journal</i>, <i>33</i>(11), 12087-12098.</p> <p style="text-align: justify;">[9] McGuire, D. K., Levine, B. D., Williamson, J. W., Snell, P. G., Blomqvist, C. G., Saltin, B., & Mitchell, J. H. (2001). A 30-year follow-up of the Dallas Bed Rest and Training Study: II. Effect of age on cardiovascular adaptation to exercise training. <i>Circulation</i>, <i>104</i>(12), 1358-1366.</p> <div id="playht-shortcode" data-shortcode=" <div id="playht-iframe-wrapper" style="display:flex; max-height:"90px"; justify-content:center"> <iframe allowfullscreen="" frameborder="0" scrolling="no" class="playht-iframe-player" data-appId="E9FaMfn-qe" article-url="https://www.lifespan.io/?p=134177" data-voice="en-US-BrandonNeural" src="https://play.ht/embed/?article_url=https://www.lifespan.io/?p=134177&voice=en-US-BrandonNeural&config={"width":""100%"","height":""90px"","alignment":"center","title":"Audio","message":"Hello","download_text_button":"Download"}" width=""100%"" height=""90px"" style="max-height:"90px""> </iframe> </div>"></div>

AI Outperforms AI-Assisted Doctors in Diagnostic Reasoning

<p style="text-align: justify;">In a new study, ChatGPT 4.0 <a href="https://doi.org/10.1001/jamanetworkopen.2024.40969">achieved significantly better diagnostic scores</a> when evaluating complex cases than either unassisted human physicians or physicians who consulted the chatbot [1].</p> <h2 style="text-align: justify;"><b>Bad news for human doctors?</b></h2> <p style="text-align: justify;">For millions of people, chatbots powered by large language models (LLMs) have quickly become an indispensable source of information on everything from finances to relationships. These digital aids often come across as more knowledgeable, polite, patient, and compassionate than human experts.</p> <p style="text-align: justify;">It has been questioned, however, if it is really a smart idea to turn to a robot for medical advice. In what could be a troubling sign for general practitioners, chatbots have shown they can outperform humans in this area too. <a href="https://www.lifespan.io/news/ai-beats-humans-in-answering-healthcare-related-questions/">A study from May of last year</a> found that the earlier version of ChatGPT, 3.5, handily outclassed human health professionals in answering patients’ questions. Responses from both the bot and verified physicians were graded by a panel of health experts, and the gap was striking: for instance, 27% of human answers were deemed “unacceptable” compared to just 2.6% of machine-generated ones.</p> <p style="text-align: justify;">That study had relied on doctor responses pulled from Reddit, but <a href="https://www.lifespan.io/news/googles-chatbot-does-medical-interviews-better-than-humans/">a more recent study</a> went further. Earlier this year, researchers at Google developed a dedicated model called Articulated Medical Intelligence Explorer (AMIE) and tested it against human primary care practitioners. Wide-ranging health scenarios were distributed at random, with actors playing the roles of patients who discussed their cases with either the chatbot or a human physician without knowing who was who. According to expert evaluators, AMIE outperformed its human counterparts in 24 of 26 categories, including empathy.</p> <h2 style="text-align: justify;"><b>“Meet my assistant, ChatGPT”</b></h2> <p style="text-align: justify;">In a new study published in <i>JAMA Network Open</i>, Stanford researchers stripped AI of its perceived edge in empathy and bedside manner. They eliminated the patient interaction element entirely, tasking either ChatGPT 4.0 or 50 human physicians (26 attendings and 24 residents) with diagnosing six carefully selected cases. These cases had never been published before, ensuring that the LLM could not have encountered them during training.</p> <p style="text-align: justify;">Here’s the twist: half of the doctors were allowed to consult ChatGPT. The aim was to gauge whether physicians would embrace AI as an assistant and whether doing so would improve their diagnostic reasoning. All participants could also use conventional resources like medical manuals.</p> <p style="text-align: justify;">The primary outcome was a composite diagnostic reasoning score developed by the researchers, which measured accuracy in differential diagnosis, the appropriateness of supporting and opposing factors, and next diagnostic steps. Secondary outcomes included time spent per case and final diagnosis accuracy.</p> <p style="text-align: justify;">In the end of the day, the LLM dominated yet again, with a median score of 92% per case: 14 points higher than the non-LLM-assisted human group. It also achieved 1.4 times greater accuracy in the final diagnosis. Interestingly, the group of physicians consulting the chatbot didn’t fare much better than their non-assisted peers, scoring 76% versus 74%.</p> <h2 style="text-align: justify;"><b>Why didn’t consultation work?</b></h2> <p style="text-align: justify;">The researchers had anticipated that consulting the LLM would give physicians a marked advantage, but that wasn’t the case. “Our study shows that ChatGPT has potential as a powerful tool in medical diagnostics, so we were surprised to see its availability to physicians did not significantly improve clinical reasoning,” said study co-lead author Ethan Goh, a postdoctoral scholar in Stanford’s School of Medicine and research fellow at Stanford’s Clinical Excellence Research Center.</p> <p style="text-align: justify;">Why the lackluster collaboration? The authors suggest a few reasons. First, participants weren’t simply asked to provide a diagnosis. Instead, they had to demonstrate diagnostic reasoning by suggesting three possible diagnoses and explaining how they reached their final choice. The chatbot excelled at this aspect, while humans sometimes struggled to articulate their thought processes. This echoes longstanding challenges in modeling human diagnostic reasoning in computer systems before the advent of LLMs.</p> <p style="text-align: justify;">“What’s likely happening is that once a human feels confident about a diagnosis, they don’t ‘waste time or space’ on explaining their reasoning,” said Jonathan H. Chen, Stanford assistant professor at the School of Medicine and the paper’s senior author. “There’s also a real phenomenon where human experts can’t always articulate exactly why they made the right call.”</p> <p style="text-align: justify;">Another hurdle was that physicians often dismissed valid suggestions from their AI co-pilot, a sign that overcoming the natural sense of superiority toward machines may take time.</p> <p style="text-align: justify;">Finally, the researchers noted that the chatbot’s performance hinges on the quality of the prompts it receives. The research team crafted sophisticated prompts to get the most out of ChatGPT, while human participants often used it more like a search engine, asking short, direct questions instead of providing full case details. “The findings suggest there are opportunities for further improvement in physician-AI collaboration in clinical practice and health care more broadly,” Goh said.</p> <p style="text-align: justify;">One intriguing secondary finding was that doctor-LLM pairs completed cases slightly faster than doctors working solo. While, according to the paper, the difference of slightly more than a minute was negligible, Goh argues that even a small efficiency gains could help make doctors’ lives more efficient. “Those time savings alone could justify the use of large language models and could translate into less burnout for doctors in the long run,” he said. However, more rigorous studies are needed to fully understand this potential benefit.</p> <h2 style="text-align: justify;"><b>AI will not replace doctors (until it will)</b></h2> <p style="text-align: justify;">The authors of studies like this one have been careful to emphasize that AI is not a true substitute for a human health practitioner. “AI is not replacing doctors,” Goh reassures. “Only your doctor will prescribe medications, perform operations, or administer any other interventions.”</p> <p style="text-align: justify;">Still, it may only be a matter of time before AI demonstrates superiority over human physicians in nearly every aspect of care. Furthermore, vast regions of the world currently face limited access to healthcare, leaving many people without the option of consulting a human doctor at all. In such contexts, AI could fill a critical gap. Just as some countries skipped the landline phase entirely and adopted mobile phones, they might also be the first to transition to predominantly AI-driven healthcare, facing fewer entrenched bureaucratic barriers.</p> <p style="text-align: justify;">Building on this study, Stanford University, Beth Israel Deaconess Medical Center, the University of Virginia, and the University of Minnesota have joined forces to create <a href="https://med.stanford.edu/hospitalmedicine/research/arise-network.html#page_1">AI Research and Science Evaluation (ARiSE)</a>, a network dedicated to evaluating generative AI outputs in healthcare.</p> <div class="textwidget"><div class="sep-2"></div> <div class="life-highlight-box lhbox-has-zoom-yes l-hbox-size-large l-hbox-edges-square" style="background-color: #cef0f5;"><div class="l-hbox-lower"><div class="l-hbox-lower-desc" style="color:#000;">We would like to ask you a small favor. <strong>We are a non-profit foundation</strong>, and unlike some other organizations, we have no shareholders and no products to sell you. <strong>All our news and educational content is free</strong> for everyone to read, but it does mean that we rely on the help of people like you. Every contribution, no matter if it’s big or small, <strong>supports independent journalism</strong> and sustains our future. </div><style>.rb--b05315fb522ed8 a {background-color:#1e4fba;}.rb--b05315fb522ed8 a:hover {background-color:#79bcf0;}</style><div class="l-hbox-lower-cta rb--b05315fb522ed8"><a href="https://www.lifespan.io/how-you-can-help/" target="_self" rel="noopener">Yes I will donate❤️</a></div></div></div> </div> <h2 style="text-align: justify;"><b>Literature</b></h2> <p style="text-align: justify;">[1] Goh, E., Gallo, R., Hom, J., Strong, E., Weng, Y., Kerman, H., … & Chen, J. H. (2024). Large language model influence on diagnostic reasoning: a randomized clinical trial. JAMA Network Open, 7(10), e2440969-e2440969.</p> <div id="playht-shortcode" data-shortcode=" <div id="playht-iframe-wrapper" style="display:flex; max-height:"90px"; justify-content:center"> <iframe allowfullscreen="" frameborder="0" scrolling="no" class="playht-iframe-player" data-appId="E9FaMfn-qe" article-url="https://www.lifespan.io/?p=134167" data-voice="en-US-BrandonNeural" src="https://play.ht/embed/?article_url=https://www.lifespan.io/?p=134167&voice=en-US-BrandonNeural&config={"width":""100%"","height":""90px"","alignment":"center","title":"Audio","message":"Hello","download_text_button":"Download"}" width=""100%"" height=""90px"" style="max-height:"90px""> </iframe> </div>"></div>

Can AI Predict Your Death?

<p style="text-align: justify;">Once confined to the realms of science fiction or relatively crude internet death calculators, AI-driven predictions about longevity are inching closer to reality. Questions about the accuracy and value of these forecasts remain.</p> <p style="text-align: justify;">In recent years, researchers and companies around the globe have been pursuing answers to the ultimate question: How long have we got left? These models leverage cutting-edge tools, such as artificial intelligence and machine learning, drawing on a variety of parameters to deliver statistically grounded insights.</p> <p style="text-align: justify;">Conceptually, they function like established diagnostic tools such as QRisk for heart disease or CHA₂DS₂-VASc Score for stroke risk. Yet, the debate remains: are these predictions meaningful advancements or little more than modern-day fortune-telling?</p> <h2 style="text-align: justify;"><strong>The tech behind lifespan prediction</strong></h2> <p style="text-align: justify;">With the advent of artificial intelligence, increasing numbers of tools are emerging on the market. At the same time, biotech companies, such as <a href="https://www.lifespan.io/news/ai-in-longevity-the-reality-today/">Altos Labs and BioAge Labs</a>, among others, are engaging such technologies to develop state-of-the-art therapeutics.</p> <p style="text-align: justify;">AI isn’t a one-stop fix for all challenges. The reality is that it’s a technological tool, albeit with immense potential, that utilizes sophisticated algorithms to get results, much like any other modern technology.</p> <p style="text-align: justify;">The same approach applies to lifespan prediction technologies built on AI. They engage a suite of technologies, such as:</p> <ul style="text-align: justify;"> <li><b>Neural networks. </b>These mimic the brain’s architecture, similarly to neurons making connections, and help uncover complex patterns in health and lifestyle data.</li> <li><b>Machine learning algorithms.</b> These analyze high-dimensional datasets, including genomic sequences, wearable device outputs and lifestyle choices, to establish relationships that could impact aging.</li> <li><b>Random forests</b> <b>and</b> <b>decision trees. </b>These can help to identify the critical biomarkers or lifestyle factors that influence the human lifespan.</li> </ul> <h2 style="text-align: justify;"><strong>The power of big data</strong></h2> <p style="text-align: justify;">Perhaps one of the major advantages of AI over traditional solutions hinges on its capabilities in analyzing extensive data sets. These can include:</p> <ul style="text-align: justify;"> <li><b>Lifestyle metrics</b>. By tabulating diet, exercise, sleep patterns, and other defined factors, it becomes possible to establish their roles in both healthspan and lifespan.</li> <li><b>Medical history.</b> This data can offer insights into chronic illnesses, prior interventions, and potential risk factors for the future.</li> <li><b>Genomic data.</b> Identifying hereditary risk factors and aging-related genes can establish possible risk levels.</li> <li><b>Real-time biometrics.</b> Data gathered from wearable technology, such as heart rate and oxygen levels, can provide insights to overall health longitudinally.</li> </ul> <p style="text-align: justify;">By combining these together, a bigger picture can be established that analyzes the probability of a patient developing a disease or condition or experiencing a negative health outcome within a specific period.</p> <h2 style="text-align: justify;"><strong>The relationship of risk and lifespan</strong></h2> <p style="text-align: justify;">Predicting the risks of specific diseases is not the same as predicting lifespan, and there may be ethical, moral, and legal concerns. To predict lifespan itself, companies working in this sector often choose to focus on specific metrics: biomarkers of aging.</p> <ul style="text-align: justify;"> <li><b>Epigenetic clocks. </b>These are used to evaluate DNA methylation patterns in order to estimate biological age. Tools such as GrimAge and DeepAge are already using this technology.</li> <li><b>Blood and wearable biomarkers.</b> These can be used to detect changes in inflammation or metabolism. Tthey offer real-time insights into health trajectories and risk factors.</li> <li><b>Lifestyle biomarkers. </b>These integrate diet, stress, and physical activity in order to allow an AI to suggest actionable interventions that could potentially improve lifespan.</li> </ul> <h2 style="text-align: justify;"><strong>Companies exploring lifespan prediction</strong></h2> <p style="text-align: justify;">Despite the challenges, scientific and human curiosity drive companies to seek answers to those all-important questions. Currently, multiple companies are focused on lifespan and on measuring specific risk factors.</p> <p style="text-align: justify;"><b>Life2vec</b>: This company offers a transformer-based AI model that analyzes life trajectories, predicting events such as death and health outcomes. It draws upon comprehensive datasets from six million individuals to make its predictions. These include socioeconomic, health, and behavioral data for granular predictions. According to the company’s stats, its accuracy rate is<a href="https://life2vecai.com/faq"> between 70% to 90%</a>; however, it remains unclear how this is calculated.</p> <p style="text-align: justify;"><b>AI-ECG Risk Estimation (Aire)</b>: Aire draws upon electrocardiograms (ECGs) to predict mortality risk. It does so by identifying subtle changes in the heart’s function and potential abnormalities. Estimates from the NHS show its accuracy at <a href="https://www.imperial.nhs.uk/about-us/news/ai-model-can-predict-health-risks#:~:text=The%20AI%20model%20%E2%80%93%20known%20as,)%20in%2078%25%20of%20cases.">78%</a>.</p> <h2 style="text-align: justify;"><strong>Impacts to accuracy</strong></h2> <p style="text-align: justify;">As this is a new technology, questions arise relating to its accuracy. For example, Life2vec is a transformer-based system that integrates vast datasets to predict mortality risk with a level of granularity. However, challenges remain:</p> <ul style="text-align: justify;"> <li><b>Fundamental limitations.</b> Pinpointing death remains an almost unattainable goal. It’s almost impossible to approximate perfect accuracy even with a personalized risk assessment.</li> <li><b>Data bias</b>. AI models are often trained on data sets that lack diversity, which limits their accuracy and can make them biased in certain populations. It’s likely that such models require the same sorts of adjustments as BMI calculators.</li> <li><b>Complexity of aging</b>. This is a developing field, and models will struggle to account for all factors and assign the correct weights to them. In addition, evolving factors, such as emerging illnesses, pandemics, and accidents, will always play a role in lifespan.</li> </ul> <h2 style="text-align: justify;"><strong>Ethics</strong></h2> <p style="text-align: justify;">Like the practicalities of proving accuracy and efficacy, utilizing predictive AI technology for human health has a vast range of legal and ethical implications.</p> <ul style="text-align: justify;"> <li><b>Data privacy</b>. Health data is confidential and subject to a variety of laws, depending on jurisdiction. Misuse or incorrect use could lead to situations that result in updates to healthcare laws and data protection legislation.</li> <li><b>Ownership and consent.</b> Failure to get informed consent could lead to issues with the ownership of data behind AI predictions. This issue has already arisen with companies such as 23andMe, which have faced criticism for sharing genetic data with third parties.</li> <li><b>Bias and inequality.</b> AI is designed by human programmers that might miss biased data in datasets, which could lead to inaccuracies among some populations and possible legal implications.</li> <li><b>Psychological impact</b>. Just as knowing a risk factor could have health implications, so too could knowing one’s predicted lifespan. This may cause additional unwanted health outcomes, such as anxiety, depression, and orthorexia.</li> </ul> <p style="text-align: justify;">World Health Organization (<a href="https://iris.who.int/bitstream/handle/10665/341996/9789240029200-eng.pdf">WHO</a>) has been vocal about such issues and calls for transparent algorithms and ethical frameworks to govern the use of AI tools in health.</p> <h2 style="text-align: justify;"><strong>The future of lifespan prediction</strong></h2> <p style="text-align: justify;">Advancements are on the horizon. Moving forward, the next generation of tools for enhanced biomarker analysis could seek to integrate more complex and accurate data from epigenetic clocks, wearable devices, and molecular studies. This would allow them to deliver highly personalized lifespan predictions, even if accuracy remains a point of contention.</p> <p style="text-align: justify;">In addition to this, wearable technology, such as watches or rings, could enable real-time updates, dynamically adjusting predictions based on daily health behaviors. This could foster a nudge-style approach to health management.</p> <p style="text-align: justify;">Healthspan prediction has the potential to seamlessly integrate into everyday routines, especially for consumer technology and interactions with medical practitioners. This could enable doctors to tailor healthcare treatments to include preventive care and interventions based on an individual’s projected lifespan and biomarkers.</p> <p style="text-align: justify;">Of course, there are much broader implications to implementing these technologies in day-to-day life, and they extend beyond healthcare to such things as societal issues, personal finance, and the relationship of work to life, which are also affected by enhanced lifespans.</p> <h2 style="text-align: justify;"><strong>Do we need to know the future?</strong></h2> <p style="text-align: justify;">AI’s potential to analyze data and predict outcomes is something never seen before. As the world, including healthcare, learns how to adapt to this, this knowledge should always be taken with a pinch of salt. Validating predictive tools to the level where they can be reliably used necessitates rigorous testing for accuracy and consideration of how they should be used.</p> <div class="textwidget"><div class="sep-2"></div> <div class="life-highlight-box lhbox-has-zoom-yes l-hbox-size-large l-hbox-edges-square" style="background-color: #cef0f5;"><div class="l-hbox-lower"><div class="l-hbox-lower-desc" style="color:#000;">We would like to ask you a small favor. <strong>We are a non-profit foundation</strong>, and unlike some other organizations, we have no shareholders and no products to sell you. <strong>All our news and educational content is free</strong> for everyone to read, but it does mean that we rely on the help of people like you. Every contribution, no matter if it’s big or small, <strong>supports independent journalism</strong> and sustains our future. </div><style>.rb--203fa5555759b6 a {background-color:#1e4fba;}.rb--203fa5555759b6 a:hover {background-color:#79bcf0;}</style><div class="l-hbox-lower-cta rb--203fa5555759b6"><a href="https://www.lifespan.io/how-you-can-help/" target="_self" rel="noopener">Yes I will donate❤️</a></div></div></div> </div> <div id="playht-shortcode" data-shortcode=" <div id="playht-iframe-wrapper" style="display:flex; max-height:"90px"; justify-content:center"> <iframe allowfullscreen="" frameborder="0" scrolling="no" class="playht-iframe-player" data-appId="E9FaMfn-qe" article-url="https://www.lifespan.io/?p=134141" data-voice="en-US-JennyNeural" src="https://play.ht/embed/?article_url=https://www.lifespan.io/?p=134141&voice=en-US-JennyNeural&config={"width":""100%"","height":""90px"","alignment":"center","title":"Audio","message":"Hello","download_text_button":"Download"}" width=""100%"" height=""90px"" style="max-height:"90px""> </iframe> </div>"></div>

Resveratrol, Vitamin C Drop Oxidative Stress After Menopause

<p style="text-align: justify;">In a randomized, controlled trial published in <i>Nutrients</i>, researchers tested supplementation with resveratrol, vitamin C, and a combination of both. They learned that all of the treatments had <a href="https://pubmed.ncbi.nlm.nih.gov/39519608/">a similar positive impact on oxidative stress in postmenopausal women</a> [1].</p> <h2 style="text-align: justify;"><b>Menopausal transition</b></h2> <p style="text-align: justify;">Around the world, a significant proportion of women have reached the post-menopausal stage. In Mexico, where the study was conducted, 15% of women have reaced this threshold. As life expectancy increases, this fraction will also increase in the coming years.</p> <p style="text-align: justify;">Menopause is followed by decreased antioxidant capacity, resulting in an imbalance between oxidant molecule generation and antioxidant capacity. Such imbalance creates oxidative stress (OS). During oxidative stress, oxidizing agents can attack and break down molecules that are essential to cells and tissues, such as lipids and proteins.</p> <p style="text-align: justify;">This group of researchers previously reported “that postmenopausal women present higher concentrations of OS markers than women of reproductive age” [2]. Therefore, using antioxidants seems like a reasonable strategy to reduce the detrimental effect of oxidative damage on lipids and proteins.</p> <p style="text-align: justify;">Those researchers chose <a href="https://www.lifespan.io/topic/resveratrol-benefits-side-effects/">resveratrol</a> and vitamin C because previous research had described them as having “cardioprotective, anti-sclerotic, anti-inflammatory, and antioxidant properties“ [3].</p> <p style="text-align: justify;">Resveratrol is a natural phytoestrogen and a polyphenolic flavonoid that is well tolerated and not toxic. Resveratrol was previously described to have a role in increasing both the expression and activity of antioxidant enzymes while reducing oxidative load [4, 5].</p> <h2 style="text-align: justify;"><b>Clinical trial of postmenopausal females</b></h2> <p style="text-align: justify;">The researchers conducted a pilot randomized, double-blind clinical trial. They recruited women between 50 and 60 years old who were in the early postmenopause stage and had insulin resistance.</p> <p style="text-align: justify;">Among the exclusion criteria were the use of hormone replacement therapy or drugs such as anticoagulants, metformin, bezafibrate, statins, or any antioxidant in the three months before the beginning of the study. Active smokers and women with some health conditions were also excluded.</p> <p style="text-align: justify;">The study participants were divided into one of three groups: 13 participants in the resveratrol group plus a vitamin C placebo (group A), 15 participants in the resveratrol and vitamin C (group B), and 14 participants in the vitamin C plus a resveratrol placebo (group C). Depending on the group assignment, the participants received 500 mg resveratrol capsules, vitamin C/ascorbic acid tablets, or placebo tablets for three months.</p> <h2 style="text-align: justify;"><b>Reduced oxidative stress</b></h2> <p style="text-align: justify;">First, the researchers analyzed baseline clinical and biochemical blood test results. In the intra-group analysis, baseline measurements were compared to after-treatment measurements, and no significant differences were found in measurements such as weight, BMI, glucose, insulin, lipid profile, and uric acid.</p> <p style="text-align: justify;">When groups were compared with each other after a three-month intervention, the researchers observed significantly lower total cholesterol levels and significantly higher triglyceride levels in the vitamin C group compared to the resveratrol group. The researchers also observed significantly lower triglyceride concentrations in the combined group compared to the vitamin C-only group.</p> <p style="text-align: justify;">Comparing the baseline and after-treatment levels of lipohydroperoxides (LPH), a measure of oxidative deterioration of lipids, showed a significant decrease of 33% in the combined group. The resveratrol group and the vitamin C group had 25% and 15% decreases in LPH levels, respectively. However, those differences were not statistically significant. The researchers hypothesize that it was due to the sample size being too small, and future research with a bigger sample size might lead to significant results in those groups as well.</p> <p style="text-align: justify;">The researchers also analyzed the levels of MDA, the end product of lipoperoxidation. All three groups showed statistically significant differences between initial measurement before the treatment and following the 3-month treatmnet. MDA levels were reduced by 26% in the resveratrol group, 32% in the combined group, and 38% in the vitamin C group.</p> <p style="text-align: justify;">Previous experiments conducted on rats that received resveratrol achieved similar results [6]. Similarly, a study of people under 18 taking vitamin C also showed MDA reduction [7].</p> <p><img fetchpriority="high" decoding="async" class="aligncenter wp-image-134136 size-full" src="https://www.lifespan.io/wp-content/uploads/2024/12/Resveratrol-Vit-C-1.png" alt="Resveratrol Vit C 1" width="1000" height="793" srcset="https://www.lifespan.io/wp-content/uploads/2024/12/Resveratrol-Vit-C-1.png 1000w, https://www.lifespan.io/wp-content/uploads/2024/12/Resveratrol-Vit-C-1-400x317.png 400w, https://www.lifespan.io/wp-content/uploads/2024/12/Resveratrol-Vit-C-1-499x396.png 499w, https://www.lifespan.io/wp-content/uploads/2024/12/Resveratrol-Vit-C-1-256x203.png 256w, https://www.lifespan.io/wp-content/uploads/2024/12/Resveratrol-Vit-C-1-300x238.png 300w, https://www.lifespan.io/wp-content/uploads/2024/12/Resveratrol-Vit-C-1-150x119.png 150w, https://www.lifespan.io/wp-content/uploads/2024/12/Resveratrol-Vit-C-1-480x381.png 480w, https://www.lifespan.io/wp-content/uploads/2024/12/Resveratrol-Vit-C-1-600x476.png 600w, https://www.lifespan.io/wp-content/uploads/2024/12/Resveratrol-Vit-C-1-360x285.png 360w, https://www.lifespan.io/wp-content/uploads/2024/12/Resveratrol-Vit-C-1-262x208.png 262w, https://www.lifespan.io/wp-content/uploads/2024/12/Resveratrol-Vit-C-1-555x440.png 555w" sizes="(max-width: 1000px) 100vw, 1000px" /></p> <p style="text-align: justify;">After measuring lipid damage, the researchers analyzed protein oxidative damage. A statistically significant reduction was also observed in all groups. The differences between before and after treatment measurements show 39% reduction in the combined group and 29% in both the resveratrol and vitamin C groups.</p> <p><img decoding="async" class="aligncenter wp-image-134138 size-full" src="https://www.lifespan.io/wp-content/uploads/2024/12/Resveratrol-Vit-C-2.png" alt="Resveratrol Vit C 2" width="994" height="752" srcset="https://www.lifespan.io/wp-content/uploads/2024/12/Resveratrol-Vit-C-2.png 994w, https://www.lifespan.io/wp-content/uploads/2024/12/Resveratrol-Vit-C-2-400x303.png 400w, https://www.lifespan.io/wp-content/uploads/2024/12/Resveratrol-Vit-C-2-523x396.png 523w, https://www.lifespan.io/wp-content/uploads/2024/12/Resveratrol-Vit-C-2-256x194.png 256w, https://www.lifespan.io/wp-content/uploads/2024/12/Resveratrol-Vit-C-2-300x227.png 300w, https://www.lifespan.io/wp-content/uploads/2024/12/Resveratrol-Vit-C-2-150x113.png 150w, https://www.lifespan.io/wp-content/uploads/2024/12/Resveratrol-Vit-C-2-480x363.png 480w, https://www.lifespan.io/wp-content/uploads/2024/12/Resveratrol-Vit-C-2-600x454.png 600w, https://www.lifespan.io/wp-content/uploads/2024/12/Resveratrol-Vit-C-2-360x272.png 360w, https://www.lifespan.io/wp-content/uploads/2024/12/Resveratrol-Vit-C-2-262x198.png 262w, https://www.lifespan.io/wp-content/uploads/2024/12/Resveratrol-Vit-C-2-555x420.png 555w" sizes="(max-width: 994px) 100vw, 994px" /></p> <p style="text-align: justify;">There were also differences in antioxidant capacity. However, this time, there was an increase of 30% for the combined group and 28% for the vitamin C group following the treatment compared to baseline.</p> <p><img decoding="async" class="aligncenter wp-image-134139 size-full" src="https://www.lifespan.io/wp-content/uploads/2024/12/Resveratrol-Vit-C-3.png" alt="Resveratrol Vit C 3" width="1000" height="799" srcset="https://www.lifespan.io/wp-content/uploads/2024/12/Resveratrol-Vit-C-3.png 1000w, https://www.lifespan.io/wp-content/uploads/2024/12/Resveratrol-Vit-C-3-400x320.png 400w, https://www.lifespan.io/wp-content/uploads/2024/12/Resveratrol-Vit-C-3-496x396.png 496w, https://www.lifespan.io/wp-content/uploads/2024/12/Resveratrol-Vit-C-3-256x205.png 256w, https://www.lifespan.io/wp-content/uploads/2024/12/Resveratrol-Vit-C-3-300x240.png 300w, https://www.lifespan.io/wp-content/uploads/2024/12/Resveratrol-Vit-C-3-150x120.png 150w, https://www.lifespan.io/wp-content/uploads/2024/12/Resveratrol-Vit-C-3-480x384.png 480w, https://www.lifespan.io/wp-content/uploads/2024/12/Resveratrol-Vit-C-3-600x479.png 600w, https://www.lifespan.io/wp-content/uploads/2024/12/Resveratrol-Vit-C-3-360x288.png 360w, https://www.lifespan.io/wp-content/uploads/2024/12/Resveratrol-Vit-C-3-262x209.png 262w, https://www.lifespan.io/wp-content/uploads/2024/12/Resveratrol-Vit-C-3-555x443.png 555w" sizes="(max-width: 1000px) 100vw, 1000px" /></p> <h2 style="text-align: justify;"><b>No improvements in insulin resistance</b></h2> <p style="text-align: justify;">Despite previous research linking oxidative state and insulin resistance, none of this study’s groups demonstrated statistically significant differences in insulin resistance.</p> <p style="text-align: justify;">The researchers discuss previous studies on humans that, except for one, all reported that resveratrol does not affect insulin resistance. Those studies looked at different populations of participants with different health conditions and variable durations and doses of treatment.</p> <h2 style="text-align: justify;"><b>Similarity of all groups</b></h2> <p style="text-align: justify;">The authors caution when interpreting the results, as the research has some limitations. For example, the generalizability of the results from a homogenous group of participants, including only females from the Valley of Mexico metropolitan area, was limited.</p> <p style="text-align: justify;">Additionally, the researchers did not include a control, untreated group. However, as the authors explain, their question addressed how the combined treatments compare with a single treatment and whether there is possible synergy between them. Their experimental setup allowed for those comparisons and comparisons of the changes that the women experienced compared to baseline.</p> <p style="text-align: justify;">The researchers conclude that despite the differences in the effects of different measurements of oxidative stress, “none of the three interventions were superior to the others.”</p> <div class="textwidget"><div class="sep-2"></div> <div class="life-highlight-box lhbox-has-zoom-yes l-hbox-size-large l-hbox-edges-square" style="background-color: #cef0f5;"><div class="l-hbox-lower"><div class="l-hbox-lower-desc" style="color:#000;">We would like to ask you a small favor. <strong>We are a non-profit foundation</strong>, and unlike some other organizations, we have no shareholders and no products to sell you. <strong>All our news and educational content is free</strong> for everyone to read, but it does mean that we rely on the help of people like you. Every contribution, no matter if it’s big or small, <strong>supports independent journalism</strong> and sustains our future. </div><style>.rb--203fa5555717f3 a {background-color:#1e4fba;}.rb--203fa5555717f3 a:hover {background-color:#79bcf0;}</style><div class="l-hbox-lower-cta rb--203fa5555717f3"><a href="https://www.lifespan.io/how-you-can-help/" target="_self" rel="noopener">Yes I will donate❤️</a></div></div></div> </div> <h2 style="text-align: justify;"><b>Literature</b></h2> <p style="text-align: justify;">[1] Montoya-Estrada, A., García-Cortés, A. Y., Romo-Yañez, J., Ortiz-Luna, G. F., Arellano-Eguiluz, A., Belmont-Gómez, A., Lopéz-Ugalde, V., León-Reyes, G., Flores-Pliego, A., Espejel-Nuñez, A., Solis-Paredes, J. M., & Reyes-Muñoz, E. (2024). The Administration of Resveratrol and Vitamin C Reduces Oxidative Stress in Postmenopausal Women-A Pilot Randomized Clinical Trial. <i>Nutrients</i>, <i>16</i>(21), 3775.</p> <p style="text-align: justify;">[2] Montoya-Estrada, A., Velázquez-Yescas, K. G., Veruete-Bedolla, D. B., Ruiz-Herrera, J. D., Villarreal-Barranca, A., Romo-Yañez, J., Ortiz-Luna, G. F., Arellano-Eguiluz, A., Solis-Paredes, M., Flores-Pliego, A., Espejel-Nuñez, A., Estrada-Gutierrez, G., & Reyes-Muñoz, E. (2020). Parameters of Oxidative Stress in Reproductive and Postmenopausal Mexican Women. International journal of environmental research and public health, 17(5), 1492.</p> <p style="text-align: justify;">[3] Breuss, J. M., Atanasov, A. G., & Uhrin, P. (2019). Resveratrol and Its Effects on the Vascular System. International journal of molecular sciences, 20(7), 1523.</p> <p style="text-align: justify;">[4] Xia, N., Daiber, A., Förstermann, U., & Li, H. (2017). Antioxidant effects of resveratrol in the cardiovascular system. British journal of pharmacology, 174(12), 1633–1646.</p> <p style="text-align: justify;">[5] Livraghi, V., Mazza, L., Chiappori, F., Cardano, M., Cazzalini, O., Puglisi, R., Capoferri, R., Pozzi, A., Stivala, L. A., Zannini, L., & Savio, M. (2024). A proteasome-dependent inhibition of SIRT-1 by the resveratrol analogue 4,4′-dihydroxy-trans-stilbene. Journal of traditional and complementary medicine, 14(5), 534–543.</p> <p style="text-align: justify;">[6] Kong, D., Yan, Y., He, X. Y., Yang, H., Liang, B., Wang, J., He, Y., Ding, Y., & Yu, H. (2019). Effects of Resveratrol on the Mechanisms of Antioxidants and Estrogen in Alzheimer’s Disease. BioMed research international, 2019, 8983752.</p> <p style="text-align: justify;">[7] Ismy, J., Soebadi, A., Mangunatmadja, I., Monica, M., Sari, T. T., & Yuliarti, K. (2024). Role of antioxidants in reducing oxidative stress and seizure frequency in drug-resistant epileptic patients. Narra J, 4(2), e790.</p> <div id="playht-shortcode" data-shortcode=" <div id="playht-iframe-wrapper" style="display:flex; max-height:"90px"; justify-content:center"> <iframe allowfullscreen="" frameborder="0" scrolling="no" class="playht-iframe-player" data-appId="E9FaMfn-qe" article-url="https://www.lifespan.io/?p=134126" data-voice="en-US-CoraNeural" src="https://play.ht/embed/?article_url=https://www.lifespan.io/?p=134126&voice=en-US-CoraNeural&config={"width":""100%"","height":""90px"","alignment":"center","title":"Audio","message":"Hello","download_text_button":"Download"}" width=""100%"" height=""90px"" style="max-height:"90px""> </iframe> </div>"></div>

Turn Biotechnologies Announces ERA™ Bone Marrow Study

“Multiple studies of clinical bone marrow transplant outcomes have identified that patients who receive donor stem cells from young donors have superior outcomes, owing to more durable correction of underlying blood and immune defects, with lower risks of graft dysfunction and donor clonal hematopoiesis,” said Timothy Olson, MD, PhD, principal investigator of this study, and Medical Director of the Blood and Marrow Transplant and Co-Chief of the Cellular Therapy & Transplant Section at Child

Mehmood Khan on Aging Policy and Collaboration

<p style="text-align: justify;">I first met Dr. Mehmood Khan in 2022 at the inaugural Longevity Summit Dublin, where organizers Aubrey de Grey and Martin O’Dea made a bold decision to include policy and advocacy discussions alongside the traditional focus on longevity research. Like many others in the audience, I was captivated by the forceful, engaging, and compelling one-man show that Khan delivered with apparent ease. “This is how public persuasion is done,” I remember thinking. “We need more people like him on our side.”</p> <p style="text-align: justify;">Khan had already enjoyed an illustrious career before joining the longevity movement, holding high-profile roles such as Vice Chairman and Chief Scientific Officer of Global Research and Development at PepsiCo and President of Global R&D at Takeda Pharmaceuticals. However, Khan is not just a high-profile bureaucrat. He has a solid background in science and healthcare, having served as Chief of the Endocrine Division at Hennepin County Medical Center in Minnesota and later as a faculty member in endocrinology at the Mayo Clinic and Medical School.</p> <p style="text-align: justify;">It’s this rare combination of qualifications and interests that led him to his current role as CEO of <a href="https://hevolution.com/">Hevolution</a>, the world’s best-funded healthspan-focused non-profit, created by, no less, a royal Saudi decree. Despite being a relatively new player in the field, Hevolution has swiftly established itself as a dominant force, leveraging its overflowing war chest both boldly and strategically.</p> <p style="text-align: justify;">Hevolution is the largest sponsor of the $100-million-plus XPRIZE Healthspan and supports dozens of researchers in the fundamental biology of aging across the globe. It has also begun investing in longevity startups. With so much happening, an interview with Mehmood Khan was long overdue. We sat down to discuss Hevolution’s vision, its progress, and his thoughts on the future of the field.</p> <h2 style="text-align: justify;"><b>Let’s start with your personal journey to the longevity field. I know it’s an unusual one.</b></h2> <p style="text-align: justify;">Unlike most experts, I haven’t been in the field long directly. Indirectly, it’s been my whole career. I was an endocrinologist, practiced at the Mayo Clinic and the University of Minnesota, saw a lot of patients with diabetes, metabolic disease, obesity. Much of my early research, if you go back 25 years or so, was around metabolic disease and obesity, and this was before aging was itself considered a discipline.</p> <p style="text-align: justify;">My career has progressed from being focused in a specific subject area to being fascinated by how you can impact health at a large scale, which is what bridged my interest from medicine to food. I had a faculty appointment in food science as well as in medicine because I trained in food science at the College of Food Science and Agriculture. This was 35 years ago, and that progressed to thinking about global challenges, whether it’s food supply, water, or the carbon footprint of large industries like PepsiCo.</p> <p style="text-align: justify;">The chance to converge all of this together crystallized with the whole field of healthspan. When I started looking at this field, everyone was still primarily talking about longevity. And it was clear to me that longevity is not the target here – healthspan is. What we’ve spent the last years doing, and it’s been my privilege to lead the team, is to focus Hevolution much more on healthspan than longevity.</p> <h2 style="text-align: justify;"><b>This distinction between healthspan and longevity seems important to you. Yes, we have seen increases in longevity but not in healthspan in recent decades, which isn’t good, but do we really have to uncouple these terms to such an extent?</b></h2> <p style="text-align: justify;">I think sometimes you have to uncouple it because it’s the vocabulary that you use that gets the traction with policymakers. I’ve spoken to a lot of health ministers, finance ministers, and several heads of state over the last few years. If we make this purely about getting people to live longer, it becomes interpreted as more dependency – more people to take care of, bigger pension bills, bigger health bills for Medicare, National Health Service in the UK, Japan, China, wherever you go.</p> <p style="text-align: justify;">If you talk about longevity, you end up with not a lot of interest at the very senior policymaker level. Health ministers, yes, but they’re not the ones holding the purse strings. You’ve got to convince the finance ministers, the labor ministers, the economy ministers that this is of national interest. It isn’t about people living longer for the sake of living longer, but about productivity.</p> <p style="text-align: justify;">If you talk to individuals (and we’ve surveyed them), and you ask, “Do you want to live longer?” – that won’t be their number one priority. But if you ask, “Do you want to live healthy as long as possible?” – yes, almost unanimously. So, as scientists, we may not uncouple it, but the average person on the street understands those two things differently.</p> <p style="text-align: justify;">More importantly, policymakers view these as two different things. I think it’s important for us as leaders in the field to say that our primary goal is to keep populations healthy as long as possible. The secondary benefit of that might be that people live longer. But if we start with the argument that we want people to live longer, that’s not going very far. It hasn’t gone for decades.</p> <p style="text-align: justify;">If you focus on life extension, you inevitably get sucked into debates such as “Is this against God (if you’re religious) or nature?” You get into all other kinds of ethical debates. But the minute you say, “I want people to live healthy for as long as possible,” there’s no disagreement about that.</p> <h2 style="text-align: justify;"><b>Yes, that makes a lot of sense. Let’s now talk about Hevolution, which emerged in the field just a couple of years ago and has since become a major player.</b></h2> <p style="text-align: justify;">Hevolution was created by a royal order from the King. It is chaired by His Royal Highness, Prince Muhammad, the Crown Prince and Prime Minister. It was the vision to take on a global challenge that would benefit as many people on the planet as possible. Healthy aging touches every human being. It’s a global challenge that affects every country, including the kingdom, so it’s very relevant locally across the Gulf, but globally as well.</p> <p style="text-align: justify;">It was set up as a nonprofit because the primary driver was to fund the science to move the field forward, accelerate the science into the marketplace with patient capital willing to take risks, and put it under a nonprofit umbrella. So, the incentives are aligned – we want our venture capital arm to succeed, attract other investors, and grow the size of the pie.</p> <p style="text-align: justify;">One part of that mission statement was particularly important to us: to extend healthy lifespan for the benefit of all. That’s something that is uniquely possible under the umbrella of a nonprofit. We want to democratize everything we do. We put that lens on everything we evaluate. Whatever we do, we look at it through the scalability lens. We’re not interested in technologies that might touch a few privileged people in the world, even though that may be where it starts. We look at it and ask ourselves, “How does this scale? Is there a path?”</p> <p style="text-align: justify;">Naturally, we care about another important issue: the bioethics of healthspan extension. It’s not just asking the question “Can it be done?” but also “Should it be done?”, and that shouldn’t be left just to the scientists. I am a scientist, and I should not be the one leading that conversation. I’m a strong believer that this should be something that experts in ethics are engaging with from day one.</p> <p style="text-align: justify;">Before we funded a single science grant, we put together a global ethics team, and that, to my knowledge, is the first time global bioethicists have been convened around the field of aging and asked to guide us and hold us accountable. Arthur Caplan, who is at the helm, is a world expert on ethics. He’s the chair of bioethics at NYU, previously Johns Hopkins, New Orleans. Julian Savulescu, founding chair of bioethics at Oxford, is another example.</p> <h2 style="text-align: justify;"><b>This is a very interesting aspect of Hevolution I admit I’ve never heard of. I think many aging researchers don’t really want bioethicists around – they see them mostly as a nuisance. Can you name some of the insights this team has come up with?</b></h2> <p style="text-align: justify;">There are a couple of things that they’ve started to push us to think about. One is, “How do you make this inclusive?” Not only the output, but the research. Initially, like everybody else, we were looking at the world and saying, let’s fund North America, the UK, but usually absent at the research table are people from the African subcontinent, South America, Latin America. Our bioethicists asked us why.</p> <p style="text-align: justify;">If you’re really going to address global aging, you have to understand aging in the context of the world. The continent that’s going to have the most elderly people in the world in the next 50 years is Africa, and yet, you almost never see people from Africa at aging meetings. It was a good push. We went to the WHO to explore possible collaborations: they’ve got a much better footprint there than we do. How do we collaborate with them? I don’t have an answer yet, but we’re working on it.</p> <p style="text-align: justify;">Another example is how we think about aging as a process in terms of when we would intervene versus not intervene. When is the earliest you should intervene? If you ask biologists, they’ll tell you that aging as a process starts around 14 days after conception. Should you intervene in an embryo? Should you intervene in a child?</p> <p style="text-align: justify;">I had the privilege of giving a couple of lectures at Yale Law School three or four years ago on the distinction between law and ethics in business. Something you learn when you look at this as a scientist (the lawyers already know that) is that the law is only a memorialization of a society’s ethics. Then, isn’t it our job as scientists to help convene that ethics discussion and move it forward alongside the scientific field rather than have it follow?</p> <h2 style="text-align: justify;"><b>What’s your philosophy in choosing projects?</b></h2> <p style="text-align: justify;">First, we want to fund the underlying science in the biology of aging. That’s our primary target. We don’t want to just fund another research study on Alzheimer’s, diabetes, dementia, osteoporosis. There’s lots of research going on and lots that’s been done. Most of it has come from working backwards from the end case. They say, now you’ve got osteoporosis, what can I do to increase your bone mineral density? If you have dementia, what can I do to slow it down? Not what can I do to prevent it.</p> <p style="text-align: justify;">So, understanding the biology is the key. The second thing is understanding how and when to intervene. When you start asking those questions, one thing that will surface is that we still don’t really know how to measure aging as a biological process. Yes, there’s DNA methylation, there’s this and that. Every six months you’ll hear of a new biomarker, then another, but most of them come from relatively small studies correlated with one or two variables. We have A-glycohemoglobin (HbA1c) for diabetes, but not its equivalent for aging. We know what cardiovascular risk profiling looks like based on biomarkers – LDL, HDL – but we don’t have the same for aging.</p> <p style="text-align: justify;">So, one bucket is how do you measure aging? This has to be predictive and correlate with treatment. Ideally, a good biomarker will reverse with treatment. This is why we funded the global meeting on biomarkers of aging at Cold Spring Harbor earlier this year. We brought together the world’s experts, both clinicians and biomarker experts and regulators, to start a series of discussions.</p> <p style="text-align: justify;">I strongly believe that we should fund this research and facilitate this debate. For instance, we should think about how we make biomarkers of aging open source. You know, if LDL cholesterol had been patented, we probably wouldn’t have statins.</p> <p style="text-align: justify;">Right now, we’ve got about 150 labs and 200 principal investigators around the world that are funded by us. We’re also funding partnerships where we’re a partner in the scientific grants. Basically, just like the NIH, we say, send us your best idea. We then send it to independent review; we don’t like to review the grants ourselves. I don’t need to take phone calls saying, “Hey, Mehmood, I just submitted this grant. What do you think?” I wouldn’t even know what you’re talking about because it goes to an independent panel.</p> <p style="text-align: justify;">I’ll give you an example. We’re interested in proteostasis at the cellular and tissue level. How do we bring the best minds together? In this case, we went to Richard Morimoto at Northwestern, one of the world’s academic leaders in proteostasis, and said, if you would put your dream team together and develop a series of research plans around that, we’ll fund you. And he did. It’s almost 30 million dollars. That’s an example of a partnership where we targeted the area, found the world expert, and asked that PI to put together a multi-center team.</p> <p style="text-align: justify;">The value of that is he’s going to collaborate with people who might have been competing with him for grants in the past. Now he can say, “Listen, we can get funding together if we come together.” That’s the catalyst role that we play as Hevolution. We’re catalyzing the field by catalyzing collaboration.</p> <h2 style="text-align: justify;"><b>Another way you’ve been catalyzing the field is through XPRIZE Healthspan, where Hevolution is the lead and single-largest funder. Can you tell me more about this collaboration? In particular, since you talked about biomarkers, what do you think about their idea of reversal of age-related loss of function as the endpoint?</b></h2> <p style="text-align: justify;">It’s very exciting to see how they’re incentivizing the world. They’ve done this successfully in other fields, putting the best minds, ideas, and resources to answer the question. This is the moonshot, this is the challenge: show us 10 years of reversal (of loss of function). Let’s go!</p> <p style="text-align: justify;">Evidence shows that in prizing mechanisms such as XPRIZE, the multiplier is about 8 to 10. For every dollar of the prize money, the collective investment brought in by the competitors is eight to ten times that. For a chance to win 80 million I’m going to put in two million, three million from grants or investors. This scenario repeats itself a hundred times over, everybody’s competing, and finally, the 80-million prize draws 800 million into that field.</p> <p style="text-align: justify;">That’s the beauty of this model. The reason we support it is that, in the back of my mind, a hundred-million-dollar prize means a billion dollars will potentially be mobilized. That’s the leverage. Every team that’s competing is going to either find investors, or government funding, or donors.</p> <p style="text-align: justify;">Regarding the specific biomarkers, when we went to the table, I said that nobody from Hevolution or any sponsor should be involved in defining the endpoints or sit on the judging committee. We helped find independent judges, we helped put together the endpoint committee to come up with the definition, but that was the limit of our involvement.</p> <p style="text-align: justify;">I was delighted when Professor Patrick Maxwell accepted. He’s the Dean of the Medical School at the University of Cambridge – a world-class researcher. Ironically, some of the people we approached turned us down for a very interesting reason. When they learned about the details of the prize, they said they couldn’t do it because they now wanted to compete. We still counted that as a win.</p> <h2 style="text-align: justify;"><b>Tell me about the upcoming second Hevolution Summit. What is special about this particular longevity conference?</b></h2> <p style="text-align: justify;">Actually, we did a small regional one early in 2023 in partnership with the National Academy of Medicine, and that one was focused on the Gulf area. So, it’s our third event of this type but the second Healthspan Summit.</p> <p style="text-align: justify;">At the first Healthspan Summit, we brought a lot of people together – it was bigger than anybody expected. We had people with subject matter expertise and people who were there because they were curious. The delightful part is we had people travel from all over the world, and we didn’t pay anybody to speak – no honorarium. We said, if you want to come and speak, it’s a privilege, and we’ve held that bar.</p> <p style="text-align: justify;">People loved the fact that we convened experts from different disciplines. We had regulators talking with investors, talking with scientists. People also appreciated the depth of the discussion on all the topics.</p> <p style="text-align: justify;">For the second summit, we’re taking the best of what we did and making it better. Now we have a chance to tell the world what we’ve accomplished since the first one. We can showcase research programs we’ve funded, partnerships – not ourselves, but we get the experts, the funded scientists to stand up and talk about their field.</p> <p style="text-align: justify;">We’ve now announced three companies we’ve invested in. We can showcase not only what those investments are but why we’ve invested in them. By then we may have announced more as well. We look to bring investors and these startups even closer together for matchmaking.</p> <p style="text-align: justify;">We’ll have updates from the XPRIZE – by then, we’ll be able to show the world how many teams there are, where they’re located, what types of fields they’re involved in, what science they’re interested in. The second summit is about the proof points.</p> <p style="text-align: justify;">The challenge I have right now is focus. Think about what I just shared with you: 2000 grants reviewed, 200 PIs funded, three companies announced, potentially five partnerships. I can’t put everybody on stage. It’s a good problem to have, but I think the world wants to hear from these people. They don’t want to hear from me.</p> <p style="text-align: justify;">The last piece, which I think will be the most exciting in the future, is matchmaking between our ecosystem of scientists. One thing we can do better than any government funding agency is cross borders. We can fund teams across borders much more easily than the NIH or the MRC because their priorities lie first and foremost within their own borders. We’re trying to cross these borders.</p> <h2 style="text-align: justify;"><b>I have heard you on several occasions talking about the need to work across the entire ecosystem, including with public opinion and decision makers. However, I understand that Hevolution hasn’t funded any projects in that particular field. Why is that?</b></h2> <p style="text-align: justify;">We’re very careful. We see ourselves as advocating for the field, convening different experts, but we’re not a lobby. We can’t legally lobby, nor do we want to.</p> <p style="text-align: justify;">However, we’ve had several policymakers, ministers, former ministers, attending our meetings – in the UK, in the US, in the Middle East. We’ve had very senior people from industry: Jon Symonds, Chairman of GlaxoSmithKline, was there as an example. Numerous CEOs from big pharma, small pharma, all engaging.</p> <p style="text-align: justify;">This means we have a chance to bring these parties together and hope that will shape the discourse around policy. We’re seeing early signs of that traction. Recently, I had a meeting right here in Riyadh with a former health minister. He was on a formal visit, but he asked his staff to arrange a private lunch meeting with me. That tells us that people like him are looking to Hevolution as a credible source, they are interested.</p> <p style="text-align: justify;">I was delighted to hear that when ARPA-H was announced by President Biden, one of the pillars this year was going to be aging. That’s a huge win for the field. Nobody’s going to be able to put in the sort of resources that the U.S. federal government can: the NIH’s budget is 44-plus billion dollars. Put 10 percent of that toward aging, and you’ve made a massive impact on the field’s progress.</p> <h2 style="text-align: justify;"><b>How optimistic are you about the near future of our field?</b></h2> <p style="text-align: justify;">I’m quite optimistic for several reasons. One, it’s a public health imperative. Two, it’s an economic imperative. Three, the science is now optimistically telling us that something can be done about it. You can have the first two, but if nothing can be done about it, so what?</p> <p style="text-align: justify;">The fourth reason is your field – the media. Today, I see three bodies in the media. One is mostly about the throw-away terms, the sound bites, those are people who don’t do their homework. Whatever the latest vitamin cure is, they’ll push it. That hurts our field. The second is the outlets that not only understand the science but find a way to communicate it to the readers who might not have a scientific background. The third is core science – the fact that Nature now has Nature Aging is huge. One of the top two journals in the world having a whole series on aging tells you something.</p> <h2 style="text-align: justify;"><b>What then frustrates you? What bottlenecks do you see that you’d love to change in terms of public opinion, regulation, the scientific environment?</b></h2> <p style="text-align: justify;">I see two major things. One is that sometimes, people in this field get over-enthusiastic and ahead of their own data. While I love passion and energy, the challenge is the risk to credibility. If you suddenly start making statements like, “In my lifetime, you’re going to live to be 150,” it sets an expectation and that hurts the field. Let’s not get ahead of ourselves. That frustrates me. Let’s stick with the evidence. Let the data push this field forward.</p> <p style="text-align: justify;">The old African proverb we often quote is “If you want to go fast, go alone. If you want to go far, take everybody with you.” Sometimes people in our field forget this wisdom. This is going to take a village. It’s a team sport. It’s going to take multiple players in different scientific and non-scientific disciplines. We’ve got to bring them together.</p> <p style="text-align: justify;">Just trying to create likes on social media in the short term gets a lot of publicity, sometimes gets you stardom, but that’s usually short-lived. Sometimes in that process, one forgets that it’s about the field, not oneself. I’ve been a CEO for a long time. I’ve been running large organizations and small organizations. One of the things you learn as a senior executive, whether at organizations as big as PepsiCo or as small as a biotech company, is that it’s always about the field, the business, the enterprise, not oneself. And if you remember that, you can move mountains.</p> <div class="textwidget"><div class="sep-2"></div> <div class="life-highlight-box lhbox-has-zoom-yes l-hbox-size-large l-hbox-edges-square" style="background-color: #cef0f5;"><div class="l-hbox-lower"><div class="l-hbox-lower-desc" style="color:#000;">We would like to ask you a small favor. <strong>We are a non-profit foundation</strong>, and unlike some other organizations, we have no shareholders and no products to sell you. <strong>All our news and educational content is free</strong> for everyone to read, but it does mean that we rely on the help of people like you. Every contribution, no matter if it’s big or small, <strong>supports independent journalism</strong> and sustains our future. </div><style>.rb--49c512b4984e310 a {background-color:#1e4fba;}.rb--49c512b4984e310 a:hover {background-color:#79bcf0;}</style><div class="l-hbox-lower-cta rb--49c512b4984e310"><a href="https://www.lifespan.io/how-you-can-help/" target="_self" rel="noopener">Yes I will donate❤️</a></div></div></div> </div>

A Clinical Trial of a Three-Part Treatment for Inflammaging

<p style="text-align: justify;">Reseachers publishing in <i>Antioxidants</i> have <a href="https://www.mdpi.com/2076-3921/13/11/1391">combined three antioxidant and anti-inflammatory compounds and tested their effects in human beings</a>.</p> <h2 style="text-align: justify;"><b>Three complementing choices</b></h2> <p style="text-align: justify;"><div class="wpv-grid grid-1-1 wpv-first-level unextended animation-from-left"><div class="topic-box-item" style="background-color:#fff"><a href="https://www.lifespan.io/topic/inflammaging/" class="topic-thumb-link"><div class="topic-box-thumb-wrap topic-thumb-align-left"><div class="topic-box-thumb" style="background:url(https://www.lifespan.io/wp-content/uploads/2020/09/bone-microbes.jpg) no-repeat center center;background-size: contain;"><img fetchpriority="high" decoding="async" width="800" height="450" src="https://www.lifespan.io/wp-content/uploads/2020/09/bone-microbes.jpg" class="attachment-full size-full wp-post-image" alt="CGI image of the gut and microbiome" srcset="https://www.lifespan.io/wp-content/uploads/2020/09/bone-microbes.jpg 800w, https://www.lifespan.io/wp-content/uploads/2020/09/bone-microbes-400x225.jpg 400w, https://www.lifespan.io/wp-content/uploads/2020/09/bone-microbes-704x396.jpg 704w, https://www.lifespan.io/wp-content/uploads/2020/09/bone-microbes-256x144.jpg 256w, https://www.lifespan.io/wp-content/uploads/2020/09/bone-microbes-300x169.jpg 300w, https://www.lifespan.io/wp-content/uploads/2020/09/bone-microbes-150x84.jpg 150w, https://www.lifespan.io/wp-content/uploads/2020/09/bone-microbes-480x270.jpg 480w, https://www.lifespan.io/wp-content/uploads/2020/09/bone-microbes-600x338.jpg 600w, https://www.lifespan.io/wp-content/uploads/2020/09/bone-microbes-360x203.jpg 360w, https://www.lifespan.io/wp-content/uploads/2020/09/bone-microbes-262x147.jpg 262w, https://www.lifespan.io/wp-content/uploads/2020/09/bone-microbes-555x312.jpg 555w, https://www.lifespan.io/wp-content/uploads/2020/09/bone-microbes-768x432.jpg 768w" sizes="(max-width: 800px) 100vw, 800px" /></div></div></a><a class="topic-info-link" href="https://www.lifespan.io/topic/inflammaging/"><div class="topic-box-title">What is Inflammaging? Chronic Inflammation and Aging</div><div class="topic-box-desc">One of the aging processes consists of a chronic, smoldering background of inflammation that researchers call “inflammaging”.<br><span class="topi-read-more">Read More</span></div></a></div></div></p> <p style="text-align: justify;">The first component the researchers included was AM3, a compound that is core to the Inmunoferon supplement and is an immunomodulator that has been found in trials to aid against infections [1]. Some prior work has found that AM3 also assists against immunosenescence [2]. However, as these researchers note, little work has been done in that area, and that work did not establish whether or not it could do anything to curtail age-related immune dysfunction.</p> <p style="text-align: justify;">The second component was spermidine, a polyamine that has been reported to improve the cellular maintenance process known as autophagy, thereby also ameliorating immunosenescence [3]. Spermidine has also been reported to assist in gut function by returning macrophage polarization to a less inflammatory state [4].</p> <div class="wpv-grid grid-1-1 wpv-first-level unextended animation-from-left"><div class="topic-box-item" style="background-color:#fff"><a href="https://www.lifespan.io/topic/spermidine-benefits-side-effects/" class="topic-thumb-link"><div class="topic-box-thumb-wrap topic-thumb-align-right"><div class="topic-box-thumb" style="background:url(https://www.lifespan.io/wp-content/uploads/2021/08/shutterstock_409760461.jpg) no-repeat center center;background-size: contain;"><img decoding="async" width="1000" height="667" src="https://www.lifespan.io/wp-content/uploads/2021/08/shutterstock_409760461.jpg" class="attachment-full size-full wp-post-image" alt="Grapefruit is a source of spermidine." srcset="https://www.lifespan.io/wp-content/uploads/2021/08/shutterstock_409760461.jpg 1000w, https://www.lifespan.io/wp-content/uploads/2021/08/shutterstock_409760461-400x267.jpg 400w, https://www.lifespan.io/wp-content/uploads/2021/08/shutterstock_409760461-594x396.jpg 594w, https://www.lifespan.io/wp-content/uploads/2021/08/shutterstock_409760461-256x171.jpg 256w, https://www.lifespan.io/wp-content/uploads/2021/08/shutterstock_409760461-300x200.jpg 300w, https://www.lifespan.io/wp-content/uploads/2021/08/shutterstock_409760461-150x100.jpg 150w, https://www.lifespan.io/wp-content/uploads/2021/08/shutterstock_409760461-480x320.jpg 480w, https://www.lifespan.io/wp-content/uploads/2021/08/shutterstock_409760461-600x400.jpg 600w, https://www.lifespan.io/wp-content/uploads/2021/08/shutterstock_409760461-360x240.jpg 360w, https://www.lifespan.io/wp-content/uploads/2021/08/shutterstock_409760461-262x175.jpg 262w, https://www.lifespan.io/wp-content/uploads/2021/08/shutterstock_409760461-555x370.jpg 555w" sizes="(max-width: 1000px) 100vw, 1000px" /></div></div></a><a class="topic-info-link" href="https://www.lifespan.io/topic/spermidine-benefits-side-effects/"><div class="topic-box-title">Spermidine: Benefits, Research, and Side Effects</div><div class="topic-box-desc">Found in grapefruit, spermidine is a polyamine. Some research suggests that spermidine may slow down aging and promote healthy longevity. <br><span class="topi-read-more">Read More</span></div></a></div></div> <p style="text-align: justify;">The third component was hesperidin, a flavonoid that recent prior work had found to have potential effects against multiple diseases, including hepatitis [5] and several metabolism-related disorders, such as diabetes [6], obesity [7], and non-alcoholic fatty liver disease [8]. The researchers hold that these effects most likely originate from its effects against inflammation, such as its suppression of the senescence-related protein MMP-9 [9], and on immune response [10].</p> <p style="text-align: justify;">All three of these ingredients are sold in various parts of the world as supplements and are generally considered nontoxic. No side effects were noted in this study.</p> <h2 style="text-align: justify;"><b>Effects on inflammation, oxidation, and immune function</b></h2> <p style="text-align: justify;">A total of 35 healthy people aged between 30 and 60 years old completed this study, which lasted for two months. The doses of these three compounds are distinctly different: 150 milligrams of an AM3-containing compound and 50 milligrams of hesperidin were included alongside only .6 of a milligram of spermidine.</p> <p style="text-align: justify;">As their primary target, the researchers utilized ImmunolAge, an immune system-based metric that calculates such factors as neutrophil activity and natural killer activity [11], as their measurement of biological age. They noted that the participants in both the placebo and treatment groups had, on average, an ImmunolAge of 20 years over chronological age, which the researchers ascribed to the stress and anxiety that the participants were reporting at baseline.</p> <p style="text-align: justify;">The placebo effect was not statistically significant, while ImmunolAge was significantly decreased in the supplement group by approximately 10 years. While this finding is strongly positive, the researchers also note that this was still higher by a decade than the participants’ chronological ages.</p> <p style="text-align: justify;">This difference in ImmunolAge was due to stronger responsiveness of both neutrophils and lymphocytes along with an increase in phagocytosis, the ability of immune cells to engulf and consume pathogens. In general, the cells were more responsive to perceived threats and more willing to attack them. Despite these benefits to other immune cell types, natural killer cells were unaffected.</p> <p><img decoding="async" class="aligncenter wp-image-134107 size-full" src="https://www.lifespan.io/wp-content/uploads/2024/12/Immune-Cell-Responsiveness.png" alt="Immune Cell Responsiveness" width="1000" height="721" srcset="https://www.lifespan.io/wp-content/uploads/2024/12/Immune-Cell-Responsiveness.png 1000w, https://www.lifespan.io/wp-content/uploads/2024/12/Immune-Cell-Responsiveness-400x288.png 400w, https://www.lifespan.io/wp-content/uploads/2024/12/Immune-Cell-Responsiveness-549x396.png 549w, https://www.lifespan.io/wp-content/uploads/2024/12/Immune-Cell-Responsiveness-256x185.png 256w, https://www.lifespan.io/wp-content/uploads/2024/12/Immune-Cell-Responsiveness-300x216.png 300w, https://www.lifespan.io/wp-content/uploads/2024/12/Immune-Cell-Responsiveness-150x108.png 150w, https://www.lifespan.io/wp-content/uploads/2024/12/Immune-Cell-Responsiveness-480x346.png 480w, https://www.lifespan.io/wp-content/uploads/2024/12/Immune-Cell-Responsiveness-600x433.png 600w, https://www.lifespan.io/wp-content/uploads/2024/12/Immune-Cell-Responsiveness-360x260.png 360w, https://www.lifespan.io/wp-content/uploads/2024/12/Immune-Cell-Responsiveness-262x189.png 262w, https://www.lifespan.io/wp-content/uploads/2024/12/Immune-Cell-Responsiveness-555x400.png 555w" sizes="(max-width: 1000px) 100vw, 1000px" /></p> <p style="text-align: justify;">This increase in immune responsiveness was accompanied by significant decreases in circulating inflammation. The well-known inflammatory factors TNF-α and IL-1β were significantly decreased, while the anti-inflammatory factor IL-10 was increased. However, the inflammatory factor IL-6 was also increased.</p> <p style="text-align: justify;">Oxidative stress was also significantly affected by this supplement combination. The natural antioxidant glutathione was found to be more active, while the amount of used, oxidized glutathione in the blood was decreased.</p> <p style="text-align: justify;">Moreover, the researchers hold that this supplement combination has significant effects on oxi-inflammaging, a combination of oxidative stress and inflammaging that has been suggested to have significant effects on lifespan [12].</p> <h2 style="text-align: justify;"><b>More research needed</b></h2> <p style="text-align: justify;">While this was a randomized, controlled trial with significant positive results, it was a pilot trial of only 35 people, not a Phase 2 or larger Phase 3 trial. This trial solely used an immune system-based calculation as a proxy for biological age; no epigenetic clock was used, and other lifespan-related biomarkers were not obtained. Cellular senescence, which the researchers had mentioned and was likely to be affected by the circulating biomarkers studied here, was also not directly analyzed. This study was conducted on a middle-aged group; it is unclear whether or not older people would have responded in the same way.</p> <p style="text-align: justify;">The researchers also noted that such factors as diet were not altered, with participants encouraged to continue their usual eating habits, and it was unclear how many natural antioxidants the participants were already consuming. Additionally, it is infeasible to determine if such a supplement combination can actually extend lifespan in healthy people through direct analysis, and the researchers recommend animal studies in further work.</p> <div class="textwidget"><div class="sep-2"></div> <div class="life-highlight-box lhbox-has-zoom-yes l-hbox-size-large l-hbox-edges-square" style="background-color: #cef0f5;"><div class="l-hbox-lower"><div class="l-hbox-lower-desc" style="color:#000;">We would like to ask you a small favor. <strong>We are a non-profit foundation</strong>, and unlike some other organizations, we have no shareholders and no products to sell you. <strong>All our news and educational content is free</strong> for everyone to read, but it does mean that we rely on the help of people like you. Every contribution, no matter if it’s big or small, <strong>supports independent journalism</strong> and sustains our future. </div><style>.rb--85d17af5821b68 a {background-color:#1e4fba;}.rb--85d17af5821b68 a:hover {background-color:#79bcf0;}</style><div class="l-hbox-lower-cta rb--85d17af5821b68"><a href="https://www.lifespan.io/how-you-can-help/" target="_self" rel="noopener">Yes I will donate❤️</a></div></div></div> </div> <h2 style="text-align: justify;"><b>Literature</b></h2> <p style="text-align: justify;">[1] JA, G. M., & Schamann, F. (1992). Immunologic clinical evaluation of a biological response modifier, AM3, in the treatment of childhood infectious respiratory pathology. <i>Allergologia et Immunopathologia</i>, <i>20</i>(1), 35-39.</p> <p style="text-align: justify;">[2] Villarrubia, V. G., Koch, M., & MC, C. C., González, S. and Alvarez-Mon, M.(1997) The immunosenescent phenotype in mice and humans can be defined by alterations in the natural immunity reversal by immunomodulation with oral AM3. <i>Immunopharmacology and Immunotoxicology</i>, <i>19</i>, 53-74.</p> <p style="text-align: justify;">[3] Zhang, H., & Simon, A. K. (2020). Polyamines reverse immune senescence via the translational control of autophagy. <i>Autophagy</i>, <i>16</i>(1), 181-182.</p> <p style="text-align: justify;">[4] Niechcial, A., Schwarzfischer, M., Wawrzyniak, M., Atrott, K., Laimbacher, A., Morsy, Y., … & Spalinger, M. R. (2023). Spermidine ameliorates colitis via induction of anti-inflammatory macrophages and prevention of intestinal dysbiosis. <i>Journal of Crohn’s and Colitis</i>, <i>17</i>(9), 1489-1503.</p> <p style="text-align: justify;">[5] Li, S., Hao, L., Hu, X., & Li, L. (2023). A systematic study on the treatment of hepatitis B-related hepatocellular carcinoma with drugs based on bioinformatics and key target reverse network pharmacology and experimental verification. <i>Infectious Agents and Cancer</i>, <i>18</i>(1), 41.</p> <p style="text-align: justify;">[6] Mirzaei, A., Mirzaei, A., Khalilabad, S. N., Askari, V. R., & Rahimi, V. B. (2023). Promising influences of hesperidin and hesperetin against diabetes and its complications: a systematic review of molecular, cellular, and metabolic effects. <i>EXCLI journal</i>, <i>22</i>, 1235.</p> <p style="text-align: justify;">[7] Xiong, H., Wang, J., Ran, Q., Lou, G., Peng, C., Gan, Q., … & Huang, Q. (2019). Hesperidin: A therapeutic agent for obesity. <i>Drug design, development and therapy</i>, 3855-3866.</p> <p style="text-align: justify;">[8] Morshedzadeh, N., Ramezani Ahmadi, A., Behrouz, V., & Mir, E. (2023). A narrative review on the role of hesperidin on metabolic parameters, liver enzymes, and inflammatory markers in nonalcoholic fatty liver disease. <i>Food Science & Nutrition</i>, <i>11</i>(12), 7523-7533.</p> <p style="text-align: justify;">[9] Lee, H. J., Im, A. R., Kim, S. M., Kang, H. S., Lee, J. D., & Chae, S. (2018). The flavonoid hesperidin exerts anti-photoaging effect by downregulating matrix metalloproteinase (MMP)-9 expression via mitogen activated protein kinase (MAPK)-dependent signaling pathways. <i>BMC complementary and alternative medicine</i>, <i>18</i>, 1-9.</p> <p style="text-align: justify;">[10] Camps-Bossacoma, M., Franch, À., Pérez-Cano, F. J., & Castell, M. (2017). Influence of hesperidin on the systemic and intestinal rat immune response. <i>Nutrients</i>, <i>9</i>(6), 580.</p> <p style="text-align: justify;">[11] Martínez de Toda, I., Vida, C., Díaz-Del Cerro, E., & De la Fuente, M. (2021). The immunity clock. <i>The Journals of Gerontology: Series A</i>, <i>76</i>(11), 1939-1945.</p> <p style="text-align: justify;">[12] Miquel, J. (2009). An update of the oxidation-inflammation theory of aging: the involvement of the immune system in oxi-inflamm-aging. <i>Current pharmaceutical design</i>, <i>15</i>(26), 3003-3026.</p> <div id="playht-shortcode" data-shortcode=" <div id="playht-iframe-wrapper" style="display:flex; max-height:"90px"; justify-content:center"> <iframe allowfullscreen="" frameborder="0" scrolling="no" class="playht-iframe-player" data-appId="E9FaMfn-qe" article-url="https://www.lifespan.io/?p=134105" data-voice="en-US-BrandonNeural" src="https://play.ht/embed/?article_url=https://www.lifespan.io/?p=134105&voice=en-US-BrandonNeural&config={"width":""100%"","height":""90px"","alignment":"center","title":"Audio","message":"Hello","download_text_button":"Download"}" width=""100%"" height=""90px"" style="max-height:"90px""> </iframe> </div>"></div>

Rejuvenation Roundup November 2024

A Senolytic Accelerates Reproductive Aging in Aged Mice: In a new study, researchers tested the impact of the senolytic drug ABT-263 on the reproductive systems of old female mice. ABT-263 treatment did not rescue age-related changes in hormonal levels, further depleted ovarian reserves, and didn’t improve most of the tested signs of reproductive aging. Preventing Alzheimer’s Proteins From Accumulating: Boosting a key autophagy-related protein discourages a core component of Alzheimer’s fr

‘Longevity protocols: We’re not chasing rainbows’

Methuselah Foundation CEO David Gobel on why wild cards and binary answers make for interesting longevity bets. Founders Longevity Forum is set to make waves in Singapore, bringing together a distinguished lineup of global leaders in clinical innovation, academic research and investment. With a focus on advancing knowledge about the rapidly growing longevity sector, especially across the Asia-Pacific region, the event promises to foster dynamic discussions and collaboration. As interest in t

Ergothioneine supplementation shows promise in slowing cognitive decline

A dietary antioxidant demonstrated potential neuroprotective benefits in pilot study individuals with mild cognitive impairment. A pilot study, conducted by researchers at the National University of Singapore and recently published in The Journal of Alzheimer’s Disease, investigated the safety and efficacy of ergothioneine supplementation in delaying cognitive decline. This randomized, double-blind, placebo-controlled study enrolled 19 participants aged 60 and older with MCI, who were alloca

Biotech raises $11m to advance regenerative osteoarthritis drug into Phase 3

Doron Therapeutics claims a single injection of its drug can deliver improvements in knee pain and function, with long-lasting effects. Clinical stage biotech Doron Therapeutics has successfully raised $11 million in a Series A funding round to advance its work in degenerative musculoskeletal conditions. The funding is intended to allow the company to commence a Phase 3 clinical trial of its lead program, MOTYS, an intra-articular biologic drug for the treatment of symptomatic knee osteoarth

Delivering longevity medicine in a primary care setting

Singapore clinic ‘experiment’ demonstrates a potential path towards democratization of longevity medicine. Nestled in the densely populated streets of Singapore, a longevity clinic with a difference is quietly conducting its work. At a glance, Bartley Clinic appears to offer many of the diagnostic and prevention services offered by high-end, concierge clinics around the world, but it’s doing so in a primary care setting. The brainchild of Dr Hisham Badaruddin, Bartley Clinic is a general

Lithuania takes step forward in European aging research

Membership of SHARE-ERIC and Government support enable Lithuanian researchers to contribute to aging research and policy shaping. Lithuania has officially become a full member of the Survey of Health, Ageing and Retirement in Europe – European Research Infrastructure Consortium (SHARE-ERIC), a pivotal platform for research on aging across the continent. This development, enabled by the Lithuanian government, aims to position the country at the forefront of aging research, and grants Lithuanian

Trump nominates Jim O’Neill as Deputy Secretary of Health

O’Neill’s nomination represents a step forward for the longevity sector, one that could influence the trajectory of aging research and its integration into public health frameworks Whether his appointment (assuming confirmation) leads to meaningful regulatory reforms or a broader acceptance of aging as a target for intervention remains to be seen; however, his deep ties to the field provide an encouraging signal for those invested in advancing healthspan and reducing the societal burden of age-r

Building an Atlas of Human Ovarian Aging

In this new study, the researchers used human ovarian tissues from four young (23-29 years) and four reproductively aged (49-54 years) healthy donors and performed two types of sequencing: one that provides a gene expression profile and another that provides information about chromatin accessibility across the genome. Sequencing data analysis identified eight clusters representing all major somatic cell types in the ovary. The proportion of each cell type differed between young and aged ovaries,