Translating Aging

Sergey Jakimov is the Managing Partner and co-founder of LongeVC, one of Europe's most active longevity-focused venture capital firms, currently raising its second fund targeting $250 million.In this episode, Chris and Sergey explore the investment landscape shaping longevity biotechnology today. They discuss LongeVC's pragmatic approach to longevity investing—focusing on disease-modifying therapies rather than targeting aging itself—and why this strategy has been successful across their portfolio. Sergey shares insights from major successes including Rubedo's partnership with Beiersdorf and Turn Bio's deal with HanAll, explaining what these deals signal about pharma's evolving interest in longevity approaches. The conversation covers critical topics for researchers and entrepreneurs: common pitfalls in academic spin-offs, the importance of clear regulatory pathways, and how the upcoming patent cliff is creating new opportunities for early-stage biotechs in the longevity space.Listeners will gain valuable insights into what makes a longevity company investable, how to navigate the transition from academic research to commercial venture, and why solving age-related diseases one by one may ultimately lead to a holistic understanding of aging itself.The Finer Details:Sergey's journey from aspiring neurosurgeon to deep tech entrepreneur to longevity investorLongeVC's pragmatic philosophy: targeting specific diseases rather than aging as a wholeThe convergence of biotech, regenerative medicine, and AI in the longevity spaceKey criteria for early-stage investment: disease indication, balanced teams, clean IP transferWhy "five scientists in a room" and "great mouse data" don't make an investable companyThe importance of platforms having their own pipelines, not just service modelsHow LongeVC's scientific advisory board (including Alex Zhavoronkov, Vadim Gladyshev, Thomas Rando) evaluates investmentsSuccess stories: Rubedo's senolytic partnership and Turn Bio's epigenetic reprogramming dealThe changing dynamics between pharma and biotech driven by patent cliffs and urgency to find the "next GLP-1"Regulatory strategies: focusing on specific endpoints rather than aging broadlyMaking longevity medicine accessible through disease-focused approaches and data-driven validationPersonal motivation: Sergey's experience as a rare disease patient and the urgency of advancing treatmentsQuotes:"Longevity as an industry is by far the industry with the biggest added value out there, because that is the issue that we all share. Without solving these things, none of the other stuff really matters—not FinTech, not blockchain, not sustainability.""Five scientists in a room generally don't make a company. Prolonging rodent lives does not make a company either.""The ultimate longevity drug version 1.0 would be a therapeutic which has an original disease indication, which also has somehow cracked the mechanism of action that would be translatable across several age-related disease domains.""It is extremely arrogant for the space to say that we're not interested in age-related diseases, like we're not interested in curing the diseases. That's traditional biotech. We're not that. We are the longevity space.""Pharma is still thinking in terms of assets rather than processes. It is almost impossible to sell a process to them... What pharma still wants is the result of that capacity actually coming to life.""At the point when something has happened to you and a rare disease has happened to you... you're only equipped with that standard of treatment that is currently available and that has made it to the clinic.""I think the presence of the FDA as this kind of gatekeeper-type agency saying, 'No, you cannot go after aging in a...

In this special episode, host Chris Patil (VP-Media, BioAge) moderates a live panel discussion at the 25th Bay Area Aging Meeting at UCSF, bringing together six leading voices across the aging research ecosystem to tackle one of the field's most critical challenges: how to move promising discoveries from the laboratory to therapies that can benefit patients.The distinguished panel spans academia, industry, and scientific publishing, featuring Janine Sengstack (CEO, Junevity), Saul Villeda (Professor, UCSF), Jodi Nunnari (Director, Bay Area Institute of Science, Altos Labs), Sebastien Thuault (Chief Editor, Nature Aging), Anne Brunet (Professor, Stanford), and Nir Barzilai (Professor, Albert Einstein College of Medicine). Together, they explore the most promising research directions for clinical impact, the revolutionary tools enabling modern aging research, and the structural challenges that must be overcome to bring longevity therapies to market.Listeners will gain insights into the emerging science of cellular rejuvenation, the importance of systemic factors in aging, how to balance high-risk discovery with practical drug development, and the cultural shifts needed to better prepare the next generation of scientists for translational work. The panel also addresses the regulatory challenges of targeting aging itself as an indication and offers candid advice for young researchers navigating this rapidly evolving field.The Finer Details:Emerging research directions with the greatest clinical potential: cellular senescence, rejuvenation and repair, DNA methylation clocks, and understanding what makes aging biomarkers tickThe revolution in cellular and spatial resolution tools and how single-cell technologies are revealing cell-type-specific aging responsesSystemic factors and the remarkable plasticity remaining in aging organisms that can be unlocked through interventionsThe critical importance of starting with human data and working backward to validate targets and approachesChallenges unique to aging biotech: the need for aging-specific cellular assays, testing in older animal models, and genetic validationCultural and structural barriers between academia and industry, including the shift from mechanism-focused to mission-driven researchBalancing high-risk fundamental discovery with the practical needs of drug development and clinical translationThe regulatory landscape for aging interventions and potential pathways to FDA approval beyond traditional disease indicationsAdvice for young scientists: embracing rejection as part of the process, finding passion, working as teams, and considering diverse career paths in the growing longevity ecosystemQuotes:"Our goal as a company is to increase human health span, and the way I like to frame that more colloquially is we want to increase the number of happy, healthy years each person gets to spend on Earth." - Janine Sengstack"There is an exquisite amount of plasticity left in an aging organism, both within the tissues, within the cells. There is plasticity that we can actually tap into." - Saul Villeda"Burn bright, but don't burn out." - Jodi Nunnari"The challenge that we run into is that there are so many combinations that very quickly it would become intractable to line up enough test tubes to test them all." - Sebastien Thuault, on the complexity of aging interventions"We love our job. If not, we would not be doing it. I would do it again in a heartbeat... you get paid to play, to ask the questions that interest you, the approaches that interest you to play with who you want to—it is a fantastic job." - Saul Villeda"Our life is a life of rejection...and still, we're having fun and making an advance. So don't give up." - Nir Barzilai

Michael Ringel is the Chief Operating Officer of Life Biosciences, a biotechnology company pioneering cellular rejuvenation therapies to reverse and prevent multiple diseases of aging. Michael became COO of Life just a few months ago, but he's been advising the company since 2018. Prior to this year, he was managing director and senior partner at Boston Consulting Group (BCG), where over a 25-year career he focused on R&D and innovation initiatives across the private sector and government. He earned his PhD in biology at Imperial College London and a JD from Harvard Law, and has become an active and highly respected member of the global longevity biotech community.In this episode, Chris and Michael explore Life Biosciences' groundbreaking approach to partial epigenetic reprogramming - the "holy grail" technology that could transform how we age at cellular, tissue, and organism levels. They discuss how this approach taps into the same biology that makes babies young, Life's lead therapeutic candidate ER-100 for eye diseases, and the "pipeline in a pill" concept at the core of the geroscience hypothesis: the idea that enable single interventions based on longevity science could treat multiple age-related diseases simultaneously.The Finer Details:The biology behind partial epigenetic reprogramming and how it differs from full reprogramming to pluripotencyWhy Michael considers partial reprogramming the "holy grail" of longevity interventionsLife Biosciences' lead candidate ER-100 for glaucoma and NAION (non-arteritic anterior ischemic optic neuropathy)The innovative inducible system that allows the therapy to be turned on and off with doxycyclineWhy the eye represents an ideal starting point for reprogramming therapiesThe "pipeline in a pill" concept and geroscience hypothesis - how single interventions could treat multiple age-related diseasesParallels between the emerging longevity field and the massive GLP-1 drug market that many pharma companies missedThe role of philanthropic investment in advancing fundamental longevity researchEvolutionary theories of aging and why aging should be easily manipulableTimeline expectations for moving from single disease treatments to whole-body rejuvenationLinksLife Biosciences company websiteMichael Ringel's ARDD talk

Dr. Janine Sengstack is the Chief Scientific Officer and co-founder of Junevity, a company created in 2023 with the mission of extending health span and lifespan through what they term "Cell Reset therapeutics." The company recently secured $10 million in seed funding.In this episode, Chris and Janine explore the innovative platform Janine developed during her PhD work in Hao Li's lab at UCSF, which now forms the foundation of Junevity's therapeutic approach. They discuss how the company uses computational and experimental methods to identify transcription factors that can "reset" cells from a diseased, aged state back to a healthy state while maintaining cell identity. Janine explains how Junevity is developing siRNA therapeutics targeting these transcription factors to treat age-related diseases, with a focus on metabolic conditions and other disorders that impact longevity.The Finer Details:The development of the Reset platform during Janine's PhD work and its evolution into Junevity's therapeutic approachHow transcription factors act as "managers" in cells, regulating many other genesUsing AI and machine learning to identify the right transcription factors to target based on disease and tissue-specific dataThe validation process for siRNA therapeutic candidates in cell and animal modelsJunevity's focus on diseases with large-scale transcriptional dysregulation, including type 2 diabetes, obesity, muscle wasting diseases, and osteoarthritisThe advantages of siRNA as a therapeutic modality for targeting traditionally "undruggable" transcription factorsJunevity's business strategy and timeline, with clinical trials potentially beginning in 2026Quotes:"We tackled this high risk, high reward PhD project: we were inspired by the Yamanaka factors to say, 'Okay, let's find brand new transcription factors that we can target to take cells from a diseased, old state and bring them back to a healthy state while keeping them the same cell type, never turning them into a stem cell.'""Transcription factors: I like to think of them as managers in the cell.""We think the advent of modern AI and machine learning tools to better analyze what they regulate, plus siRNA as a really well-proven therapeutic modality, really unlocks the ability to target transcription factors and really make powerful therapeutics with them.""We're thinking about using transcriptional regulation as a way to come up with novel therapeutics to treat diseases that have a big impact on people's health span and lifespan.""We want to advance our programs towards development candidates, which basically means the drug entity, and move them forward towards clinical development as fast as possible.""I would love if we had multiple siRNA drugs on the market, ideally, or in late stages of development for a wide range of longevity-related diseases... We think that there's really huge potential here for making a big impact on a lot of different really complicated diseases."Linkshttps://www.junevity.com

Dr. Andrew Brack, Program Manager at the Advanced Research Projects Agency for Health (ARPA-H), discusses PROSPR (Proactive Solutions for Prolonging Resilience), an ambitious new program aimed at extending human healthspan. In this wide-ranging conversation, Chris and Andrew explore how PROSPR plans to accelerate the development of therapies that target aging itself by building the regulatory and scientific infrastructure needed to measure and improve health during aging. They discuss PROSPR's innovative approaches to in-home data collection, biomarker development, and clinical trial design that could compress decades-long studies into just three years.The Finer Details:The mission and structure of ARPA-H as a catalyst for healthcare innovationHow PROSPR aims to build "train tracks" for the longevity therapeutics industryThe program's novel approach to measuring health through intrinsic capacityStrategies for compressing clinical trials from decades to yearsThe economic impact of extending healthspan by just one yearPlans for first- and second-generation therapeutics targeting agingThe role of in-home health monitoring in future clinical trialsQuote: "We have this moral imperative to close the gap between the length that we are living and the number of years that we're living in good health."Links:PROSPR websiteProposers' Day registration

Markus Gstöttner is the CEO of Clock.bio, a company devoted to extending and improving the quality of life by reversing the harmful effects of time in our cells. In this episode, Gstöttner shares how his company is working to extend healthspan by understanding and harnessing the natural rejuvenation capabilities of stem cells. The conversation explores Clock.bio's groundbreaking approach to identifying the genes and pathways involved in cellular rejuvenation, and their vision for translating these discoveries into therapies.The Finer Details:How induced pluripotent stem cells (iPSCs) naturally resist and reverse agingClock.bio's novel platform for forcing stem cells to age and studying their spontaneous rejuvenationThe company's comprehensive genetic screen identifying over 150 rejuvenation-related genes, the Atlas of Rejuvenation FactorsStrategies for validating these discoveries and developing therapeutic applicationsThe path from discovery to clinical trials for extending human healthspan

Adam Freund (CEO) and Remi Laberge (CTO) are the founders of Arda Therapeutics, a biotechnology company developing novel therapies that selectively eliminate harmful cell populations driving chronic diseases. In this episode, they discuss their innovative approach to treating conditions like idiopathic pulmonary fibrosis by identifying and removing specific cell types that cause tissue damage, rather than trying to modify cellular behavior through traditional drug approaches.The Finer Details:The concept of pathogenic cells as drivers of chronic diseaseHow single-cell RNA sequencing enables precise identification of harmful cell populationsArda's approach to developing targeted antibody therapeuticsAdvantages of cell elimination versus pathway modificationThe potential for intermittent dosing to improve patient quality of lifeFuture applications in aging and age-related diseasesQuotes: "Cells make up tissues. Tissues make up organisms... If you have the right cell at the right place, everything looks good. If you have the wrong cell at the wrong place, doing the wrong thing, the tissue will decay.""We position our strategy as an alternative to traditional pathway targeting... changing cell behavior by blocking a single node could be quite challenging.""This is game changer for the patient experience. If we're successful, our drug will be administered once a quarter, once every six months. But during that time, this patient feels like he is not a patient. He doesn't take a drug, he's not under treatment, and doesn't have the side effect of taking those drugs.""We think that cell depletion is a broadly applicable strategy across many chronic diseases, including potentially aging itself one day.""In 10 years from now... we will know precisely which cells to eliminate. Now, will we be allowed to do it in an otherwise healthy patient? That's a different type of question."

Alex Aravanis is the CEO and co-founder of Moonwalk Biosciences, a biotechnology company pioneering precision epigenetic medicines. In this episode, Chris and Alex discuss Moonwalk's innovative approach to developing a new class of medicines aimed at treating complex diseases and potentially extending human healthspan.The Finer Details:The concept of epigenetics as the "source code" for cell statesMoonwalk's technology for analyzing and modifying the epigenomeThe company's focus on cardiometabolic diseases and adiposityComparison of Moonwalk's approach to other epigenetic reprogramming strategiesPotential applications in treating obesity and metabolic disordersThe use of AI and machine learning in epigenetic researchFuture directions and challenges for Moonwalk BiosciencesQuotes:Quotes have been lightly edited for clarity."In the past, I've heard people refer to the DNA as the blueprint of biology, and I don't quite like that analogy. I think of it as more like the hardware, and the epigenome is the source code — the epigenome is responsible for the complex coordination of different genes that lead to proteins, and the temporal aspects of those so it's really how the hardware is used to make and maintain and change different cell types.""We're opening up the epigenome as a platform for drug discovery. The vast majority of the genome is not the coding regions, but it's incredibly important in controlling gene expression. So there's a lot of biology in there to inform our selection of targets, and we think that could dramatically improve both the number of interesting targets and our ability to select targets. The data that we're creating, our expertise, and our computational tools make us amongst the best in the world at using the epigenome for drug discovery."Links:Email questions, comments, and feedback to: podcast@biohagelabs.comTranslating Aging on Twitter: @bioagepodcastBioAge website: https://bioagelabs.comBioAge Twitter: [@bioagelabs]

In this episode, Chris Patil speaks with Dr. Mehmood Khan, CEO of Hevolution Foundation, about the organization's mission to extend healthy human lifespan and better understand the aging process. Dr. Khan discusses Hevolution's unique approach to funding global scientific discovery and investing in private companies dedicated to advancing aging science. He shares insights into the challenges and opportunities in the field of longevity research, the importance of global collaboration, and the potential impact of extending healthspan on societies worldwide.The Finer Details:Hevolution Foundation's origin and missionThe importance of aging research in the context of global challengesHevolution's collaborative approach and funding strategiesChallenges in translating aging research into accessible interventionsThe need for validated biomarkers in aging researchGlobal perspectives on aging, including challenges in developing countriesThe importance of policy engagement and public awareness in advancing the fieldhttps://www.hevolution.com/

Hans Keirstead, PhD, is the Chairman of the Board at Immunis, a biotechnology company researching and developing immune secretome products to address age-driven immune deficits. In this episode, Chris and Hans discuss Immunis' approach to targeting the aging immune system as a key driver of age-related disease. They explore the potential of immune secretome factors to restore youthful immune function, the promising results from Immunis' preclinical and early clinical studies, and the future of immune-modulating therapeutics to extend healthspan.THE FINER DETAILSThe critical role of the immune system in the aging process and age-related diseaseImmunis' focus on immune precursor cell secretome factors to restore youthful immune functionPreclinical studies demonstrating the effects of Immunis' secretome product on muscle growth, metabolism, and inflammation in aged miceEarly results from Immunis' Phase 1/2a clinical trial in older adults with muscle atrophy and knee osteoarthritisThe potential for immune secretome therapeutics to treat a wide range of age-related conditions and enhance healthspanThe importance of developing affordable and accessible therapies to maximize impactQUOTES "Every manifestation of aging is immunologically mediated. It's phenomenal. When one ages, your immune system in 100% of humans gets angry, so becomes highly pro-inflammatory.""Our drug is not a stem cell. It's not an immune cell. It is the secretion set, that same secretion set that you and I have, and everyone on this earth has, that precipitously declines with age, and now we're able to restore it.""We showed that IMMUNA fundamentally changes gene expression in order to promote the expression of genes for growth and regeneration. And then it inhibits the expression of genes that inhibit growth and regeneration.""I believe that this [secretome therapeutic] is going to be taken prophylactically by most humans, every quarter or so, to keep their immune system young, keep their immune system in a prophylactically competent state.""I want this thing to be available to everyone who wants it at an extremely low price, so that we can keep people alive, so that we can keep them disease free, so they can have productive years in their golden times, in their older age."LINK TO PAPERStem cell secretome treatment improves whole-body metabolism, reduces adiposity, and promotes skeletal muscle function in aged mice

Dr. Daisy Robinton, co-founder and CEO of Oviva Therapeutics, discusses the company's innovative approach to improving women's healthspan by targeting the biology of ovarian aging. Motivated by her personal experiences and the realization that female physiology is underserved by research and medicine, Daisy outlines how menopause is a key inflection point in the acceleration of aging in women. She explains the central role of anti-Mullerian hormone (AMH) in regulating ovarian function and fertility. Oviva's lead program, a recombinant enhanced AMH protein, aims to improve IVF outcomes by synchronizing follicle growth. Excitingly, this approach could also preserve ovarian reserve to delay menopause onset, thereby extending female healthspan.Key Topics Covered:Pivoting from developmental biology to found a women's health startupOvaries as central regulators of female healthspan beyond reproductionAMH as a brake on follicle activation and loss of ovarian reserveUsing enhanced AMH to improve egg yield in poor-responding IVF patientsPotential of AMH-based therapy to delay menopause and slow agingMenopause as the single greatest known accelerator of agingEconomic and societal impact of extending female healthspanDistinguishing reproductive longevity from overall women's healthViewing fertility as a marker of overall health and wellbeing

Dr. Noah Davidsohn, co-founder and CSO of Rejuvenate Bio, discusses the company's innovative work using gene therapies to treat age-related diseases in dogs and humans. In his conversation with host Chris Patil, he explains his recent groundbreaking study showing that partial cellular reprogramming with Yamanaka factors extended lifespan and healthspan in very old mice. Noah then outlines Rejuvenate's clinical pipeline, including targeting longevity pathways like FGF-21 for heart disease and combining TGF-beta inhibition with klotho for osteoarthritis. By choosing secreted factors deliverable with liver-targeted gene therapy, Rejuvenate hopes to circumvent delivery challenges. Noah conveys an inspiring vision of adding healthy years to dogs' and humans' lives.Key Topics Covered:Rejuvenate Bio's mission to reverse aging and age-related diseaseLifespan doubling in old mice with cyclic Yamanaka factor inductionControllable gene therapy system for in vivo partial reprogrammingChoice of FGF-21 for pleiotropic effects deliverable from liverLead programs for arrhythmogenic cardiomyopathy and mitral valve diseaseAdvantages of treating age-related diseases first in dogsCombination gene therapy for osteoarthritis: TGF-beta and klothoSecreted proteins enable broad effects without broad deliveryVision of expanding healthspan by "squaring the curve"Potential to keep people healthy, active and productive to 100+

30 Years of Aging Biology: A Pioneer’s Perspective (Cynthia Kenyon - VP Aging Biology, Calico Labs)Dr. Cynthia Kenyon reflects on the evolution of the longevity field over the 30 years since the publication of her groundbreaking paper, “A C. elegans mutant that lives twice as long as wild type,” a genetic analysis of one of the first single-gene mutations to extend lifespan in the worm. She recounts the initial excitement and skepticism around the idea of a pathway that regulates aging, and subsequent validation of this and related ideas in a wide range of model organisms. She also discusses her longstanding belief in the translational potential to improve human healthspan, and her experience as a co-founder of one of the first longevity biotech startups, Elixir Pharmaceuticals, in 1999. Based on her unique historical perspective—and with undiminished enthusiasm—she looks ahead to the unsolved mysteries that will propel the next generation of breakthroughs.Key ideas:Origins of looking at aging regulation in C. elegans in the 1990sage-1 and daf-2 as the first aging genesEarly resistance to the idea of studying aging at the molecular levelCloning of genes to reveal conserved longevity pathways (IIS/mTOR)Extending lifespan in invertebrates, and then miceThe connection between stress resistance to evolutionary theoryDr. Kenyon's initial belief in the translatability of aging scienceCo-founding Elixir Pharmaceuticals in 1999 to target agingCurrent optimism about interventions against agingNeed for public funding of large trials of natural compoundsExcitement about newest mechanisms like reprogrammingThe enduring promise of targeting core nutrient-sensing networksDevelopmental origins of aging rates and resilienceLinks: Email questions, comments, and feedback to podcast@bioagelabs.comTranslating Aging on Twitter: @bioagepodcastBioAge Labs Website bioagelabs.comBioAge Labs Twitter @bioagelabsBioAge Labs LinkedIn

Dr. Jamie Justice is Executive Director of the newly launched XPRIZE Healthspan, a $101 M international competition to accelerate therapeutics targeting aging biology. In conversation with host Chris Patil, Dr. Justice outlines the motivation, structure, and timeline of the prize, as well as how teams can get involved. She also explains unique aspects of this prize, including the public commentary period, how existing trials can be adapted for competition, functional endpoints, and judging criteria. She also conveys why coordination is needed to overcome barriers and drive investment in longevity R&D. Listeners will gain key insights into this ambitious initiative to catalyze progress translating research into treatments for aging.Key ideas:Why aging solutions need acceleration despite increased attentionThe role and track record of incentive competitions like XPRIZEMotivation and sponsors enabling XPRIZE Healthspan ($101M purse)Timeline from conceptualization to upcoming 7-year active competitionExpert endpoint committee setting measurable functional criteriaInitial public commentary period for radical collaboration with teamsPhases: Intent to compete, qualifying submissions, finalist selectionExisting prevention trials can add program assessmentsCommon data and protocols to validate findings across teamsGoal of demonstrating restoration of function across domainsSecondary judging criteria around accessibility, biomarkersDriving global coordination, investment, and innovationLinks: XPRIZE HealthspanEmail questions, comments, and feedback to podcast@bioagelabs.comTranslating Aging on Twitter: @bioagepodcastBioAge Labs Website bioagelabs.comBioAge Labs Twitter @bioagelabsBioAge Labs LinkedIn

Dr. Coleen Murphy is a prominent aging researcher and author of the upcoming book “How We Age: The Science of Longevity” from Princeton University Press. In this wide-ranging discussion, Coleen provides insights into her motivation for writing this book, key topics covered, and her unique perspective on the field. Key ideas:Addressing ethical concerns about studying aging and longevityDefining aging conceptually and how metrics like lifespan vs. healthspan are measuredUsing genetics, transcriptomics and other tools to understand molecular changes in agingThe prominent role of reproduction and sex differences in agingTheories on tradeoffs between reproduction and longevityGenetics of aging pathways including insulin/IGF-1, mTOR, and sirtuinsCellular processes involved in aging such as mitochondrial dysfunction, epigenetic changes, senescenceThe importance of models like C. elegans and Drosophila in aging researchOngoing research and future potential for interventions to increase healthspanThe challenge of complex science without excessive jargonHighlighting critical contributions by women scientists in the fieldOmitting personal lifestyle advice and focusing on evidence-based scienceThe rapid pace of advancement in biotech applications of longevity scienceLinks: Email questions, comments, and feedback to podcast@bioagelabs.comTranslating Aging on Twitter: @bioagepodcastBioAge Labs Website bioagelabs.comBioAge Labs Twitter @bioagelabsBioAge Labs LinkedIn

Dr. Nicholas Hertz is the co-founder and former CSO of Mitokinin, a biotech company developing therapies targeting damaged mitochondria in neurodegenerative disease. Mitokinin was recently acquired by pharmaceutical giant AbbVie. In this episode, Nick recounts the journey from academic research on PINK1 biology to founding a startup and advancing a clinical candidate. He provides insights into the drug discovery process, optimizing lead compounds, translating basic findings into therapies, and partnering with big pharma. Nick also shares lessons learned along the way about focusing on robust science, being adaptable, and maintaining ambition to help patients.Key topics covered:Background on Mitokinin’s approach of activating PINK1 to clear damaged mitochondriaFounding a company based on academic research and discoveriesNavigating from tool compounds to optimizing in vivo activity and drug propertiesUsing mitochondrial biomarkers like phospho-ubiquitin to track target engagementPartnering with AbbVie: alignment on science, IP transfer after acquisitionImportance of reproducibility, following the science to clinic-ready agentsPlanning the next neurodegeneration startup based on past experienceAdvice for startups: pick projects wisely, focus on robust science over hypeNotable Quotes: (edited slightly for clarity and length)"What PINK1 does is signal when mitochondria have gone bad and need to be cleared away.""Seeing PINK1 mutations lead to early Parkinson's cemented the link between mitochondrial health and neurodegeneration.""The biggest challenge was getting enough brain exposure and potency for in vivo efficacy.""We developed assays to measure phospho-ubiquitin levels in patient samples and use it as a pharmacodynamic marker.""With AbbVie, we were aligned on making a safe drug you'd feel comfortable giving to your own family.""I enjoyed the journey more than the destination. Now I want to get back in the lab and do more science.""Focus on projects you believe in and doing the most robust, reproducible science.""I consider failing to help patients in Phase 3 trials a failure, even if you already exited successfully."Links: Mitokinin website (this link may become obsolete as Mitokinin becomes part of AbbVie)Email questions, comments, and feedback to podcast@bioagelabs.comTranslating Aging on Twitter: @bioagepodcastBioAge Labs Website bioagelabs.comBioAge Labs Twitter @bioagelabsBioAge Labs LinkedIn

Dr. Alex Colville is the co-founder and General Partner of Age1 Ventures, a recently launched VC firm focused on funding contrarian, founder-led biotech companies aiming to extend healthy human lifespan. In this episode, Alex outlines Age1's thesis of identifying and empowering talented founders with ambitious visions for the longevity field. He shares his own journey to VC, including early interests in aging science and entrepreneurship. Alex provides an inside look at Age1's approach to community building, sourcing high-potential founders, investing at the pre-seed/seed stage, and supporting companies technologically and strategically. He also discusses Age1's very first investment in Aperture Therapeutics. Listeners will gain insights into how Age1 aims to catalyze change in the longevity biotech ecosystem.Key topics covered:Origins of Age1 in the pioneering Longevity Fund and Laura Deming's visionAlex's path from aging researcher to VC investor and community builderHow VCs raise funds from different types of investors (LPs)Age1's focus on early-stage companies and contrarian, ambitious foundersSourcing and identifying high-potential founders through networks and eventsThe importance of founder motivation and pragmatism in Age1's investmentsAge1's first investment in Aperture Therapeutics targeting neuroinflammationUnique value-add Age1 provides with specialized aging expertiseEmpowering founders by showing people "like them" can build startupsAge1's moonshot goal of enabling agency over healthspan and lifespanNotable Quotes:(quotes have been lightly edited for clarity)"A fund is a vehicle of money devoted to making investments to return capital with more money than you started with.""Once you have the money, your focus becomes finding the best founders and supporting them to increase the odds of success.""The best founders don't necessarily realize they could be a founder. We can help show people they can just dive in.""What matters most to us is not the idea, but the founder and their potential.""We want somebody with a very strong mission motivation towards aging. This core focus ends up being a huge strength of the company.""We look for a combination of pragmatism and moonshot mentality.""Our goal is to give people agency over how long they live in good health.”“Age1 needs to exist in order to convince some of the raw, ambitious talent that they can do things they don't yet know that they can do—in order to pull off moonshots.”Links: Age1Alex’s recent paperEmail questions, comments, and feedback to podcast@bioagelabs.comTranslating Aging on Twitter: @bioagepodcastBioAge Labs Website bioagelabs.comBioAge Labs Twitter @bioagelabsBioAge Labs LinkedIn

Dr. Carolina Reis Oliveira and Dr. Alessandra Zonari are the co-founders of OneSkin, a company developing science-backed skincare products to reverse skin aging at the cellular level. In this episode, Carolina and Alessandra tell host Dr. Chris Patil how OneSkin is leveraging recent advances in longevity science to create novel peptides that target senescent cells and inflammation in aged skin. Their lead ingredient, OS-1, is a peptide capable of reducing biological age and senescence burden in human skin models.They explain their rigorous discovery process, including screening peptide libraries in cellular models of skin aging, which were described in a recent paper in Nature Aging. Next, they share how they translated this scientific research into an effective, consumer-friendly skincare product line and brand. Listeners will gain insights into OneSkin's unique approach bridging cosmetics and cutting-edge geroscience.Key topics:Why skin health and appearance are important markers of overall agingThe cellular and molecular changes underlying skin agingHow most skincare products focus on temporary effects vs. targeting root causesScreening peptide libraries in cellular models to discover senolytic/senomorphic candidatesDiscovery and testing of lead peptide OS-1 in 3D skin models and human trialsValidating safety and efficacy to meet cosmetics regulatory requirementsLaunching a science-backed skincare brand and resonating with educated consumersOngoing R&D to expand into new anti-aging applications and delivery methodsQuotes:Quotes have been lightly edited for clarity."Obviously, we look at our skin from the lens of aesthetics or of beauty. But our skin is our largest organ, and its main function is to protect our whole body against pathogens and different types of environmental stressors. As the skin ages and deteriorates, the function also gets compromised."“That's one of the things that we're interested in and exploring at OneSkin: not only how to improve your appearance, but also how to improve your skin function so it can aid in your overall health.”"We realized none of the products out there were developed with the rationale of targeting aging itself.""When we treat dermal fibroblasts with this peptide, we could decrease the amount of senescent cells by 40–50%.""More and more, the population is getting educated. They don't want just marketing claims, they want to understand and trust brands that can really bring proof.""People are more open to say, okay, if I need to put something on my skin, I should use a company that's actually doing real science.""Our primary goal is to continue to be the most innovative company when it comes to skin aging, and to continue to be at the forefront of aging research applied to skin."Links: Email questions, comments, and feedback to podcast@bioagelabs.comTranslating Aging on Twitter: @bioagepodcastBioAge Labs Website bioagelabs.comBioAge Labs Twitter @bioagelabsBioAge Labs LinkedInOneSkin company pagea...

Dr. Felix Wong is a co-founder of Integrated Biosciences, an early-stage biotech company developing next-generation therapeutics for cellular rejuvenation. He is also a postdoc at MIT and the Broad Institute and was a lead author on a recent Nature Aging paper describing the use of graph neural networks to discover new senolytic compounds.In this episode, Felix and host Chris Patil have an in-depth discussion about using machine learning to accelerate drug discovery, specifically to target cellular senescence. They explore how graph neural networks were trained on screening data to evaluate large chemical spaces and identify new senolytic molecules with medicinal properties superior to those of previously known compounds.Key topics:What cellular senescence is and why selectively eliminating senescent cells may have therapeutic benefits for aging and age-related diseasesLimitations of traditional high-throughput screening approaches and the vastness of chemical spaceHow graph neural networks work and how Felix’s team trained them on senolytic screening dataApplying the models to search much larger chemical libraries and identify promising new senolytic scaffoldsExperimental validation and characterization of hits from the AI screeningThe potential to use this machine learning approach more broadly for phenotypic drug discoveryFelix’s new company Integrated Biosciences and their mission to control cellular stress responses using synthetic biology and AIQuotes:Quotes have been lightly edited for clarity."We found that machine learning models might allow us to more productively search chemical space and increase our working hit rates.""What was fascinating to us about senescence cells is that, unlike other pathologies or diseases, these cells are not really characterized by a single target.""The quality of any machine learning model is limited by the quality of the training data. And that in turn is limited by how good your screens are, and how good your understanding of the biology is."“That's really what machine learning is doing, trying to think about things in a very high dimensional manner. And then trying to build models that help to separate what is positive and what is negative.”“So what ideally we would want is for any model to be able to generalize, to be able to predict chemical scaffolds that the model has not previously seen, and positively identify those scaffolds as new senolytics.”"Ideally, we would like to treat aging and age-related diseases, just like how antibiotics treat bacterial infections."“At Integrated, we're trying to kind of look at these stress responses holistically. We think that senescence is only a piece of the bigger puzzle.”Links: Email questions, comments, and feedback to podcast@bioagelabs.comTranslating Aging on Twitter: @bioagepodcastBioAge Labs Website bioagelabs.comBioAge Labs Twitter @bioagelabsBioAge Labs LinkedInIntegrated Biosciences

Joan Mannick, CEO and co-Founder of Tornado Therapeutics, joins the podcast to discuss her company’s exciting mission of developing a new generation of rapalog compounds specifically targeting the TORC1 complex. Rapalogs are analogs of the natural compound rapamycin, which has been shown to extend lifespan and healthspan in animal models by inhibiting the TOR pathway. However, rapamycin has limitations that have prevented its widespread clinical use for aging-related conditions.Tornado aims to overcome these limitations by developing a portfolio of novel rapalogs licensed from Novartis, which were specifically designed to be more selective TORC1 inhibitors with improved drug-like properties relative to rapamycin. Early data suggests these compounds may have an improved safety profile and remain effective at treating diseases like cancer.In her conversation with host Chris Patil, Dr. Mannick provides an accessible overview of TOR signaling biology and shares insights from her extensive experience developing rapalogs. The discussion covers Tornado’s strategic approach to indications like oncology and viral infections, the process of characterizing their licensed compounds, and notable milestones on the horizon.Dr. Mannick provides an insider perspective on a compelling longevity biotech company striving to translate the promise of rapalogs into effective medicines for age-related diseases.Key topics:An overview of the TOR signaling pathway, the TORC1 and TORC2 complexes, and how the natural compound rapamycin inhibits TOR function.The benefits and limitations of using rapamycin/rapalogs clinically, and the need for more selective TORC1 inhibitors with improved drug properties.Tornado’s licensing of novel TORC1-specific rapalogs from Novartis, including early safety data.Indications that Tornado is initially pursuing, including oncology and viral infection, applying lessons learned about rapalogs over the past decade.The experience of being a “pipeline company” within the Cambrian Biopharma family, and the synergies available to companies operating within this model.The maturation of the longevity biotech fieldPromising milestones on Tornado’s horizon.Quotes:Quotes have been lightly edited for clarity."Rapamycin is a very specific inhibitor of this critical protein mTOR that regulates lifespan and healthspan."“An ideal rapalog to treat aging-related conditions and extend lifespan is predicted to be a rapalog that specifically inhibits TORC1, but leaves TORC2 alone.”"The problem with rapamycin is that it has no remaining patent life. And we really have to do the studies to see if the benefit outweighs the risks."“[Cambrian] enabled me to go very fast in terms of execution - you get a team, which is very rare when you start a startup.”"Longevity medicine is white space ready to be explored. It's an untapped area that could transform the practice of medicine."“We are picking indications where there's not just preclinical validation, but a lot of clinical validation.”“We're going to use these lessons learned to see if with a better clinical development plan, we can now develop our next generation rapalogs to enhance antiviral immunity and decrease severity of viral respiratory tract infections.”Links: Email questions, comments, and feedback to podcast@bioagelabs.comTranslating Aging on Twitter: @bioagepodcastBioAge Labs Website...