Translating Aging

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, COO of Life Biosciences and a seasoned expert with a PhD in biology, discusses groundbreaking advancements in cellular rejuvenation therapies. He delves into partial epigenetic reprogramming, dubbed the 'holy grail' for longevity, explaining how it rejuvenates cells while preserving functionality. The conversation touches on the promising ER-100 therapy aimed at combating vision loss and the collaborative spirit essential in biotech innovations. Ringel also emphasizes the potential of longevity interventions to tackle multiple age-related diseases simultaneously.

Janine Sengstack, Chief Scientific Officer and co-founder of Junevity, discusses innovative siRNA therapeutics aimed at treating age-related diseases. She delves into her research at UCSF that led to the development of the Reset platform, which targets transcription factors to 'reset' aging cells back to health. Janine explains the role of AI in identifying these key factors and the ambition behind Junevity's plans for human clinical trials by 2026, aiming to tackle conditions like diabetes and obesity while extending healthspan and lifespan.

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, CEO of Clock.bio, brings his diverse experience from public service and cultured meat entrepreneurship to the forefront of stem cell research. He discusses groundbreaking work on induced pluripotent stem cells (iPSCs) that may reverse aging effects. Gstöttner reveals significant findings from a genetic screen identifying over 150 rejuvenation-related genes. The conversation also highlights the potential of strategic partnerships and drug repurposing in advancing therapies aimed at extending healthspan and tackling age-related diseases.

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