Translating Aging

Marco Quarta is co-founder and Chief Scientific Officer of Rubedo Life Sciences, a precision-therapeutics company developing medicines that target the pathological cell states that drive age-associated disease. Marco's first appearance on the show was three years ago, in February 2023 (Episode 35), when Rubedo was a much earlier-stage company committed to the then-contrarian premise that "the senescent cell" is not a single entity but a heterogeneous family of cell states that needs to be deconvoluted at the single-cell level. In March 2026, Rubedo reported preliminary Phase 1b/2a clinical data for its lead candidate, RLS-1496, a first-in-class topical GPX4 modulator. Marco returns to the show to discuss what survived contact with human biology.In this episode, Chris and Marco unpack the readout from Rubedo's basket trial across four skin indications — psoriasis, atopic dermatitis, actinic keratosis, and photoaged skin — and the biology that underlies it. RLS-1496 came clean on safety in all four indications, with significant efficacy signals despite small patient numbers and short (20–30 day) treatment courses. More provocatively, the clinical and translational data have pushed Marco to redefine what kind of drug this actually is. Rather than a next-generation senolytic, GPX4 modulation appears to act as a state-gating intervention: it triggers ferroptosis in deeply senescent cells that have already crossed a redox threshold, while inducing a hormetic "redox reset" in stressed-but-recoverable cells that restores them to a healthier state. Marco proposes a new category to capture this dual action — adaptive senotherapeutics, or senoadaptive drugs — distinct from senolytics and senomorphics.The conversation traces the arc from Rubedo's founding thesis to a clinically validated platform (ALEMBIC, the AI-enabled single-cell multiomics engine that surfaced GPX4 as a target), through the strategic logic of leading with skin, into the broader question every longevity-biotech founder eventually has to answer: when does a disease-by-disease franchise become a credible preventive geroscience platform? Marco lays out the GLP-1 analogy explicitly — an anchor indication and a label-expansion roadmap that could carry GPX4 modulation from dermatology into respiratory, neurodegenerative, and metabolic disease, and ultimately into the use case where biomarkers of cellular senescence flag patients for therapy decades before disease becomes clinically apparent.The Finer Details:How Marco's 2023 contrarian view — that "senescent cells" hide a tissue- and state-specific reality — has been reinforced by the clinic, and how Rubedo's framing has shifted from "targeting senescent cells" to "targeting pathological cell states"The biology of GPX4 as a lipid-peroxidation gatekeeper, why senescent cells have intrinsic vulnerabilities (p16, p21, CDK4/6 inhibition) that make them ferroptosis-sensitive, and how Rubedo's approach differs from oncology-focused GPX4 programs at Takeda and othersThe "senoadaptive" mechanism — RLS-1496 eliminates GPX4-dependent senescent cells via ferroptosis while triggering NRF2/Keap1-driven redox reset, autophagy, and epigenetic remodeling in recoverable cells, restoring tissue trajectory from degenerative to regenerativeWhy Rubedo led with skin: clean regulatory path, accessible tissue, the ability to read out aging biology anddisease in the same trial, and a label-expansion runway into systemic indicationsPhase 1b (Europe) and Phase 2a (US) basket-trial results across psoriasis, atopic dermatitis, photoaged skin, and actinic keratosis: clean safety in 4/4 indications and significant efficacy signals — itch reduction in atopic dermatitis, decreased lesional thickness in psoriasis, target-engagement-correlated clinical improvement in photoaged skinThe richness of the translational dataset: biopsies, tape-stripping, spatial transcriptomics, proteomics, multiplex histomics, plasma biomarkers — all feeding back into ALEMBIC to refine the platformWhy actinic keratosis is the most strategically important indication — an age-related, chronic-inflammatory, precancerous condition where Rubedo can simultaneously test disease modification and biological-age reversalThe Rubedo–Beiersdorf partnership and the cosmetic vertical as a parallel commercial axisPipeline beyond skin: targeting aberrant basaloid stem cells in IPF and other pulmonary indications using different modalities (prodrugs, PROTACs, ADCs) to achieve cell-state selectivityThe longer-arc vision: senescence biomarkers as a "prediabetes-style" early signal, with senoadaptive drugs deployed decades before disease — and what a GLP-1-scale franchise might look like for GPX4 modulationQuotes:"There is not such a thing as a senescent cell — like there is not a cancer cell. And that was the initial idea. I'm glad that over time the field evolved. Now this is an accepted concept in the senotherapeutic space.""We are really talking about a dual function of RLS-1496 that can modulate the cell state depending on the adaptive response. That's why we call this — de facto — a new class of senotherapeutics. We call them adaptive senotherapeutics, or senoadaptive drugs — not a senolytic or a senomorphic, but working by modulating the cell state.""The best animal model for human therapies is human. As much as you can do preclinical work in animal models, it's always an approximation. We were able to test this directly in patients for safety, and in 4 out of 4 indications, we didn't have any safety signal.""Imagine you're taking care of a growing tree, and this tree has some dead leaves and some are a little bit stressed. If you shake the tree, the dead leaves will fall; the healthy leaves will not, because they're healthy and they resist the shake. But that shake actually gives the stressed leaves space and breathing room, and helps them to regain vitality. That's a little bit what GPX4 modulation does.""Senotherapeutics is a large, growing field — an untapped therapeutic opportunity. There is no such thing as a pan-senolytic or a pan-senotherapeutic, like there is no pan-oncotherapeutic. You need to understand the context. But these will all be part of the arsenal for true longevity medicine.""I don't see this as prevention of disease. The way I see therapies like ours, and the way the field of longevity is developing, is treating diseases decades before they develop. That's not a new concept — that's what we're doing in diabetes. You can be diagnosed with prediabetes today and reverse those biomarkers with lifestyle changes or metformin, and maybe never develop diabetes. That's exactly what we're doing here.""First of all, celebrating the first approved drugs from Rubedo — I don't think we're too far from that. But that's also a beginning, because you learn from the big momentum the GLP-1 agonists created: how a drug can start in one indication, create a new field, and prove that you can go beyond that. I hope in a few years we come back and talk about the next GLP-1 — this could be GPX4 modulators, or the senoadaptive drugs that are first in our pipeline."Links:Rubedo Life Sciences: https://www.rubedolife.comMarco Quarta's previous appearance on Translating Aging: Ep 35 — Targeting Pathologic Cells to Preserve Biological Youth

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

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

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

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]

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. 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+

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. 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. 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 pageNature Aging paper

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 bioagelabs.comBioAge Labs Twitter @bioagelabsBioAge Labs LinkedInTornado Therapeutics

This special episode features a panel discussion moderated by Chris Patil at the 2023 SynBioBeta conference. The panel brings together leaders from the synthetic biology and longevity communities to explore opportunities for collaboration and cross-pollination between these fields. Panelists discuss the talent bottleneck in longevity research, challenges in translating new discoveries into therapies, the need for improved communication and education, and a shared vision for transforming health and society. The conversation covers existing resources for learning about longevity science, as well as calls to build new communities and networks to accelerate progress. Overall, the panel makes a compelling case that by coming together, synthetic biologists and longevity advocates can achieve breakthroughs that neither field could accomplish alone.Guests:Nathan Cheng, Longevity Biotech FellowshipStephanie Dainow, Lifespan.ioDaniel Goodman, UCSFKat Kajderowicz, MIT/WhiteheadThe DetailsThe talent shortage in longevity research and need to attract people from outside the fieldChallenges in developing model systems and translating discoveries from simple organisms to humansThe role of improved communication, education and “edutainment” in enabling progressExisting online resources and communities in longevity science and synthetic biologyThe Time Fellowship and opportunities to get involved for students and early career researchersVisions for how synthetic biology could enhance longevity research, including new tools for measurement and diagnosticsHopes for progress in the short, medium and long term, from gaining years of healthspan to far future transformational changesThe importance of breaking down silos, incentivizing collaboration and taking action to achieve ambitious goalsQuotes:Quotations have been lightly edited for clarity.Nathan Cheng“A lot of people here asked me the difference between working on diseases of aging versus aging itself. And I think a lot of people aren't aware that age-related diseases like cardiovascular disease, Alzheimer's disease, even cancer — these are late-stage manifestations of the aging process itself.”“I think it's incumbent on us within the longevity community to go seek out the tool developers because they are inundated with all this interest from other players in other fields.”Stephanie Dainow“When it comes to aging, a lot of people you are under the impression that you're born, you will age there probably will be suffering, and then you will die. And that is the cycle of life. Right? That's kind of a standard. And I think this field is pushing that narrative in a direction that is uncomfortable because we're not used to it.”“Incentive structures matter. And in longevity, there aren't a lot of organizations that have products yet — forget the supplements, I'm talking about therapeutics — and that means that there aren't business development people, which means there's no selling, which means there's no marketing, which means there's no focus on articulation of the best way to create a narrative around the value prop.”Dan Goodman:“Synthetic biology has lots to offer, as far as measurement and diagnostics and being able to cheaply and at scale measure the effects of aging and the effects of longevity therapies on large populations.”“As we get more comfortable, and we get more and more skilled at deploying these tools for disease, it'll be to the point that healthy people will be willing to take these sorts of therapies. and we can do so much to modify the body and immune system to affect longevity.”Kat Kajderowicz:"Often I find folks working on problems really directly relevant to aging and longevity, but they don't consider themselves as being part of the field, or they're the only person in their lab, where they don't really have a community.""Find folks who you get along with and trust — find good mentors. There's so many great resources as well, so you can learn and get to the speed at which you are able to know which questions to ask.”Links: Email questions, comments, and feedback to podcast@bioagelabs.comTranslating Aging on Twitter: @bioagepodcastBioAge Labs Website bioagelabs.comBioAge Labs Twitter @bioagelabsBioAge Labs LinkedInLongevity Biotech FellowshipLifespan.ioTwitter handles of the panelists:Nathan Cheng - @realNathanChengStephanie Dainow - @sdainowDan Goodman - @dbgoodmanKat Kajderowicz - @KKajderowiczChris Patil - @DoNotGoGently

Jacob Kimball is the Head of Research and co-founder of NewLimit, a company aiming to develop epigenetic reprogramming therapies to treat age-related diseases and extend human healthspan.In this episode, Chris and Jacob have an in-depth discussion about NewLimit’s mission and approach. They explore how NewLimit is leveraging epigenetics and machine learning to search for new ways to reverse cell aging without changing cell identity. NewLimit is systematically testing combinations of biological factors that can reprogram cell age, using both biological experimentation and computational modeling at scale, and Jacob shares insights into the cutting-edge science and technology behind this work: how functional genomics allows NewLimit to run hundreds to thousands of experiments in a single dish, how machine learning is used in their research, and the challenges of translating epigenetic reprogramming from the lab to the clinic. Listeners will gain a deeper understanding of the promise of epigenetic reprogramming to revolutionize how we treat aging and age-related disease. The Finer Details:Epigenetics as a regulator of gene expression in cell differentiation and agingNewLimit’s mission and approach to tackling the challenges in aging research through epigenetic reprogrammingThe potential for age reversal built into our biologyHow NewLimit is using machine learning and biological experimentation in combination to generate new hypotheses and discoveriesThe potential for epigenetic reprogramming to improve the function of the aging immune system The biggest challenges in translating these discoveries to medicines, including delivery, pharmacokinetics, and ensuring safe and durable effectsA vision for how rejuvenation biotech could transform health and society in the coming decades if key breakthroughs are madeQuotes:"Epigenetics is this layer of regulation that tells your cell, ‘Which genes can I use from my genome, at which times?’""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."“Even with just those sorts of data available, we're already able to build models that perform better than randomly searching through the experimental hypothesis space, and already performed better than our rough heuristics about which interventions might be most impactful.” "We know that you can actually just express these four genes and reprogram even an old cell all the way back to an embryonic-like state, which not only changes the cell's type, the role it's playing, but also its age.""Our approach is trying to discover ways we can reprogram cell age without reprogramming cell type.""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.”"Transient interventions could have durable phenotypic benefits for a patient. However, that space hasn't been explored very richly. We know very little about just how long some of these interventions last."“I think what I'm strongly hopeful for is that, if such medicines are to exist, that you can actually increase the number of happy, healthy years each one of us gets.”“I think in the next five to 10 years, we're going to see some of the first applications of this technology and the clinics, some of the first proof points, that these interventions actually can benefit patients in a material way.”“What I hope that means for someone like myself is that the number of years in which I can plausibly consider hiking the John Muir Trail increases in a measurable way. And likewise, for those of you with other hobbies, I hope that these sorts of experiences from which we derive a lot of fulfillment increase in their abundance as a result of these medicines being available.” Links: Email questions, comments, and feedback to podcast@bioagelabs.comTranslating Aging on Twitter: @bioagepodcastBIOAGE Labs Website BIOAGELabs.comBIOAGE Labs Twitter @bioagelabsBIOAGE Labs LinkedInNewLimitNewLimit progress update (YouTube video)