Translating Aging

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:

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:

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: Links: Email questions, comments, and feedback to podcast@bioagelabs.com Translating Aging on Twitter: @bioagepodcast BioAge Labs Website bioagelabs.com BioAge Labs Twitter @bioagelabs BioAge 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: Links: XPRIZE Healthspan Email questions, comments, and feedback to podcast@bioagelabs.com Translating Aging on Twitter: @bioagepodcast BioAge Labs Website bioagelabs.com BioAge Labs Twitter @bioagelabs BioAge 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: Links: Email questions, comments, and feedback to podcast@bioagelabs.com Translating Aging on Twitter: @bioagepodcast BioAge Labs Website bioagelabs.com BioAge Labs Twitter @bioagelabs BioAge 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: Notable 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.com Translating Aging on Twitter: @bioagepodcast BioAge Labs Website bioagelabs.com BioAge Labs Twitter @bioagelabs BioAge 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: Notable 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: Age1 Alex’s recent paper Email questions, comments, and feedback to podcast@bioagelabs.com Translating Aging on Twitter: @bioagepodcast BioAge Labs Website bioagelabs.com BioAge Labs Twitter @bioagelabs BioAge 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: Quotes: 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.com Translating Aging on Twitter: @bioagepodcast BioAge Labs Website bioagelabs.com BioAge Labs Twitter @bioagelabs BioAge Labs LinkedIn OneSkin company page

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: Quotes: 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.com Translating Aging on Twitter: @bioagepodcast BioAge Labs Website bioagelabs.com BioAge Labs Twitter @bioagelabs BioAge Labs LinkedIn Integrated 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: 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.com Translating Aging on Twitter: @bioagepodcast BioAge Labs Website...

Mitchell Lee is the CEO and co-founder of Ora Biomedical, a Seattle-based biotech company using large-scale phenotypic drug screening in C. elegans to discover small molecule therapeutics that extend lifespan and healthspan. In this episode, Chris and Mitch discuss Ora's approach to drug discovery, which focuses on function and phenotype rather than specific targets or mechanisms. Using their proprietary "WormBot" platform, Ora screens thousands of compounds in parallel to identify molecules that impact lifespan, healthspan, and age-related disease phenotypes, allowing them to discover new longevity interventions in an unbiased, hypothesis-agnostic way. Key topics: C. elegan Quotes: Quotes have been lightly edited for clarity. “What really sets us apart is that we do phenotypic screening, in live animals." "If you are finding interventions that target those fundamental drivers of aging, you expect them to have multiple different impacts on age-associated diseases. But as we test more longevity interventions, we see that they also have all kinds of different impacts on non–age-associated disease models. “It’s really just taking the geroscience hypothesis seriously: If an intervention impacts aging, it’s likely to have impacts across many different disease stages, even ones that we wouldn’t necessarily think about as being related.” “We've seen examples of how this plays out with things like rapamycin. So it's really incredible the types of therapeutic benefits that can be had through these kinds of interventions.” "There's going to be a never before seen boom in enthusiasm, interest, engagement, and demand for longevity therapeutics. And what we're doing today is putting ourselves in the position where we're going to be able to meet that challenge in the next three to five years." Links: Email questions, comments, and feedback to podcast@bioagelabs.com Translating Aging on Twitter: @bioagepodcast BioAge Labs Website bioagelabs.com BioAge Labs Twitter @bioagelabs BioAge Labs LinkedIn Ora BioMedical

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: The Details Time Fellowship Quotes: Quotations have been lightly edited for clarity. Nathan Cheng Stephanie Dainow Dan Goodman:

In this episode of Translating Aging, host Chris Patil is joined by Dr. Courtney Hudson-Paz, the Founder and Program Director of the Time Initiative, an organization whose mission is to build a network of undergraduate leaders in aging biology. Courtney takes us on a journey into the world of aging biology and the mission of the Time Initiative, highlighting how this groundbreaking organization is cultivating the next generation of leaders. She shares her insights into the importance of early engagement in scientific research, the challenges faced by longevity research, and the transformative potential of geroscience. In addition, Courtney explains how the core component of the Time Initiative's program, the Time Fellowship, offers a unique opportunity for talented individuals to engage in impactful research, community-building, and mentorship. She notes the pressing need to address age-related diseases and describes the Time Initiative's efforts to create a diverse and inclusive ecosystem in aging biology. She also celebrates the fact that the contributions of ambitious young minds in the field have the potential to accelerate scientific progress and significantly reshape the field of aging biology. In this podcast, you will learn about the mission and impact of the Time Initiative and discover the strategic importance of early engagement in scientific research and the transformative potential of geroscience. You will also gain insights into the Time Fellowship, as well as the importance of building a diverse and inclusive ecosystem in aging biology, and the role it plays in shaping the future of the field. Outline Quotes: “Our motivation is really the same motivation of the field, right? We all see that the world is aging rapidly, we already have a billion people suffering from age related diseases.” "By focusing on undergrads, we're really investing in the future of the field... nurturing the next generation of leaders, innovators, and researchers." “I think what makes it unique is the focus on really early stage talent, and going after people that aren't already interested in aging, as well.” “The idea of the geroscience hypothesis is so compelling, that I feel like just the exposure is enough.” “I want to firmly establish it as a key driving force in the field of aging. I want to grow our networks of fellows, our mentors and our partners. I envision a future where our fellows are empowered by this experience through our program and they become influential figures in the field.” "The opportunities and possibility of the impact we can have in people's lives...is worth that extra funding and really deserves extra attention." "I want them conducting cutting-edge research and pioneering innovative treatments." "Stay curious. Be bold. Ask the questions, look for answers.

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: Quotes: "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...

In today’s episode, Chris is joined by Dr. Matthew "Oki" O'Connor, CEO for Scientific Affairs at Cyclarity Therapeutics, a company focused on eliminating arterial plaque, a prevalent issue in old age. Dr. O'Connor shares his insights on the causes and effects of atherosclerosis, the leading cause of death worldwide, and how aging contributes to plaque build-up. The podcast emphasizes the need for a paradigm shift in addressing cardiovascular disease and highlights the importance of new approaches to repair vessels throughout the body and brain. Together, Chris and Dr. O’Connor begin by discussing atherosclerosis, its significant impact on cardiovascular disease, and the need to understand the molecular and biochemical mechanisms underlying aging and diseases related to aging. They also cover the limitations of current clinical treatments for atherosclerosis and the importance of a paradigm shift towards new approaches that can repair vessels throughout the body and brain. Dr. O’Connor then goes on to describe Cyclarity’s unique drug, a cyclodextrin, explaining how it could be a promising solution to the harmful effects of atherosclerosis. The podcast also explores the potential of combination therapy with traditional lipid-lowering drugs to address multiple aspects of atherosclerosis. Join Chris and Dr. O’Connor here today to gain a greater understanding of the remarkable work undertaken by Cyclarity Therapeutics, the impact of aging on cardiovascular health, the need for new approaches to address atherosclerosis, and the unique drug therapy combination that may offer a promising solution, revolutionizing its treatment in the process. The Finer Details: Quotes: "Cardiovascular dysfunction, depending on which metastudy you believe, between 30 and 50% of all death on the planet is caused by the build-up of plaque in the arteries." "Atherosclerosis is the thickening of the arteries, which means in the vessel wall, you have a build up of material called plaque, which starts out as a fatty streak in the wall of a blood vessel." "There's no way to avoid the concept or the idea that a basic molecular mechanism, a biochemical mechanism of aging is going to impact many, if not all, cells and tissue systems." "By the time that you're doing vascular surgery on somebody, you've kind of lost the game. You clearly missed an opportunity to prevent a bad thing from happening in the first place." "We really need a paradigm shift to look at new approaches to addressing cardiovascular disease." "I think the average non-specialist just thinks of cholesterol as this, like, weird molecule that's in your body for some reason, but is totally bad." "Those lipid lowering drugs do actually save lives and keep atherosclerosis from getting worse faster. But we are trying to invent a better way to do it, a more elegant way to get rid of only the most toxic forms of cholesterol so that your arteries can repair themselves the way that they're engineered to." "I imagine that our treatment, at least at first, will be paired with the standard of care, which...

Dr. Marco Quarta, CEO and Co-founder of Rubedo Life Sciences, joins Chris on today’s episode to discuss his company’s strategy of targeting pathologic cells to develop therapeutics for chronic degenerative conditions. The conversation covers the evolving definition of senescence and the challenges of identifying and classifying pathologic cells, which vary across different tissues and indications. Marco also announces the upcoming Senotherapeutic Summit in November, which will bring together stakeholders from different fields to advance therapeutic research. Marco and Chris also review Rubedo Life Sciences' clinical development approach: targeting the aging process with the goal of helping healthy stem and immune cells to repair. They then go on to discuss the funding and work required for the selection and nomination of a lead candidate for a project, the importance of having access to primary clinical samples to test efficacy, and the subsequent steps of the grant awarding process. The conversation then turns to the value of having multiple programs running simultaneously. Tune in today to learn more about the ‘sneaky’ process of senescence that accelerates aging, the toxicity of these rare cells and the development of small molecules that can target them, the complexities of developing new therapies, and the value of having a robust pipeline of programs to advance therapeutic R&D. The Finer Details: Quotes: "These are aberrant cells, dysfunctional cells, and maladaptive cells that are contributing to shift the microenvironment and leading to progression of chronic degenerative conditions, driving chronic inflammation, fibrosis, stem cell depletion, and cancer." "There are no universal pathologic cells across all tissues or indications. So it really depends on your question and finding targets associated with those that you can really go after in a drug discovery pipeline to generate therapeutics." "We are hoping to push forward the conversation about what senescent cells are, how we can classify them, and how we can move forward with targeting these cells." "We are testing back to back multiple indications including for example, chronic age related atopic dermatitis and others." "And it's a very important event that we'll have major stakeholders from high level government officials and scientists and innovators business leaders and really the idea of promoting a healthy longevity and how can we accelerate this." Links: Email questions, comments, and feedback to podcast@bioagelabs.com Translating Aging on Twitter: @bioagepodcast BIOAGE Labs Website BIOAGELabs.com BIOAGE Labs Twitter @bioagelabs BIOAGE Labs LinkedIn Rubedo...

In today’s episode, Chris sits down with Kevin Caldwell, CEO, Co-Founder, and President of Ossium Health, a company that aims to improve human health and longevity through bioengineering - specifically using stem cell science to create materials for cell therapies. Together, they discuss Ossium’s approach: processing and banking of bone marrow from organ donors, which can then be cryopreserved and used for various clinical applications such as bone marrow transplants for blood cancer patients and emerging stem cell therapies. Kevin also shares details of his background as a lawyer in the stem cell industry and the potential of stem cell therapies in increasing the availability of bone marrow for treatment options. He then goes on to describe his company's clinical programs and their goal of increasing the percentage of patients who ultimately get bone marrow transplants. In addition, he reviews the company's plans for using stem cell therapies in preventive medicine, their focus on improving long-term health and lowering costs, and the company's clinical trial for treating GVHD. Finally, he says a few words about Ossium’s place in the longevity biotech sector. Listen in today to not only learn about the potential of stem cell therapies and the importance of increasing the availability of bone marrow for treatment options for blood cancer patients, but to also gain valuable insights into the future of healthcare itself. The Finer Details of this Episode: Quotes: "Every year in the United States, there are about 20,000 people diagnosed with leukemia who go looking for a bone marrow transplant… 40% of those people… ultimately do not receive a transplant. Many of those people die while looking for a donor." "Other people become so weak during the process of searching for a donor that they're taken off the list." "There are also many emerging applications of the stem cells that are native to the bone marrow, treatments for diseases of inflammation, treatments that enable people to receive organ transplants without immunosuppression." "Ossium has developed a process for processing and banking bone marrow from organ donors, cryopreserving those cells, and then doing further selection and engineering on the cells to prepare them for different clinical applications." “There's a number of steps that we have to take to go from that solid bone to bone marrow for cryopreservation.” "Our goal is to dramatically increase the percentage of patients who ultimately get bone marrow transplants." "Bone marrow transplants are not FDA regulated. They're treated like organ transplants by law." "One of the things about prevention that is most powerful is that if you achieve it, you can both improve long-term health relative to retrospective treatment, and ultimately lower cost. For us, prevention is a North Star.” “If we think about our goal of trying to broadly improve human health, one system that is involved in our response to essentially all disease is the immune system.” "At Ossium, what we're really building is

This week, we welcomes Peter Fedichev, an entrepreneur and scientist with over 20 years of experience in academic research and biotech business who has co-founded three biotech companies. He’s currently the co-founder & CEO of GERO, a longevity startup on a mission to hack aging. In this episode, Chris and Peter discuss GERO’s goal to accelerate our understanding of aging and create a therapy that will significantly extend a healthy human lifespan. First, they talk about the relationship between physics and biotech, and from there, the conversation moves to the importance of resilience in human and animal aging. Finally, Peter walks us through GERO’s drug discovery approach, how we can ‘hack’ complex dynamic systems and aging using AI, and shares his optimism about the future of aging research. The Finer Details of This Episode: Quotes: “What we can do and what I think is very good to learn how to do in biology is to understand those universal properties that do not depend on fine details of life histories.” “Obviously aging, that is a very slow process—so slow that almost everything averages out and people that are living under different conditions with totally different life histories are still living more or less the same long life.” “It's easier to rejuvenate an animal which doesn't have any resilience because resilience means the ability to get back to the norm after the intervention. If you are resilient, either a bad effect like smoking or a good effect as your future aging drug will be small, and the more resilient you are, the smaller is the effect.” “If you can only increase your lifespan once you're already unstable, the overall effect of such interventions from lifespan will be, unfortunately, incremental and limited.” “It looks like our progress in chronic diseases is very slow. It's very slow because even though genome is cheaper, we have all genetic therapies, all kinds of new therapeutic modalities, everything, but for reasons that we need to understand, it's very hard to do drugs against chronic diseases in humans.” “I think by bringing these ideas from neuroscience like your company is doing, like our company, like all our communities are doing, I think we will find ways to educate them. And who knows, maybe in five years, one of the major pharmas will start doing drugs against aging, using the techniques and the experience that we will help them to create; I think we're very close to this tipping point in the industry.” Links: Email questions, comments, and feedback to podcast@bioagelabs.com Translating Aging on Twitter: @bioagepodcast BIOAGE Labs Website BIOAGELabs.com BIOAGE Labs Twitter @bioagelabs BIOAGE Labs LinkedIn Peter Fedichev on LinkedIn GERO.AI “Unsupervised learning of aging principles from longitudinal data” Avchaciov, K., Antoch, M.P., Andrianova, E.L. et al. Unsupervised learning of aging principles...

This week, Chris welcomes Morten Scheibye-Knudsen, Associate Professor at the University of Copenhagen, who’s on a mission to understand, modulate and treat aging and age-related diseases. His research group, The Scheibye-Knudsen Lab, is trying to understand the cellular and organismal consequences of DNA damage & repair with the aim of developing interventions for aging. Morten is also one of the chairs and chief organizers of the highly successful aging research and Drug Discovery conference, ARDD. In this episode, Chris and Morten talk about interventions in the aging process and why it’s important to better understand aging in order to hopefully treat age-related diseases someday. First off, they discuss the contribution of DNA repair pathways to aging, and then Morten explains the diverging consequences of DNA damage, establishing the pivotal role that DNA damage plays in the aging process. From there they delve into how ketones work in the brain, as well as the connection between the ketogenic diet and aging. Finally, Morten shares his experience with clinical trials, the Aging Research & Drug Discovery conference, and some exciting things to look forward to in the aging field. The Finer Details of This Episode: Quotes: “I think if we're interested in being able to treat diseases and treat chronic diseases, then we really need to understand the root cause of these diseases. And most chronic, non-communicable diseases are age-associated, and aging is the largest risk factor for these diseases. So something happens during aging that makes us susceptible to disease.” “Your brain cannot metabolize fats very well, so it needs an additional food source when sugar is getting very low, and ketones are then a possible food source.” “The ketogenic diet or ketosis had been used even in Roman times. When someone had an epileptic seizure, people thought they were possessed by demons and then they put them in a cell and allowed the demons to burn themselves out. But in reality, they just left them in the cell until they went into ketosis. That's when the ketones probably broke the seizures.” “I think that we still don't exactly know how good they are in terms of aging. But I think this is a really interesting research topic because it has been very difficult to separate the, for example, reduction in blood glucose effect from the increase in ketone effect. So these exogenous ketones will really be key to dissecting that relationship.” “I think this is probably the most exciting part, I would say, of the aging field right now is the greatly expanding field of clinical trials actually targeting aging.” “I can drive a small clinical trial, but to actually get products in the hands of people and drive change for regular people, we need companies, we need industry. ” Links: Email questions, comments, and feedback to podcast@bioagelabs.com Translating Aging on Twitter: @bioagepodcast BIOAGE Labs Website bioagelabs.com BIOAGE Labs Twitter @bioagelabs BIOAGE Labs LinkedIn ARDD 2022 Website:

Optimizing Healthspan through Longevity Medicine (Dr. Andrea Maier – The Center for Healthy Longevity) Dr. Andrea Maier is an internal medicine specialist, geriatrician, and researcher whose work focuses on age-related disease, cellular senescence, and the translation of longevity science into clinical practice. Among her academic appointments are professorships at the Free University, Amsterdam and the Netherlands, the University of Melbourne in Australia, and the National University of Singapore, where she also serves as the co-director of the Center for Healthy Longevity. On today’s episode, Dr. Maier joins host Chris Patil to discuss longevity medicine, her goals for building credibility in this emerging specialty, and how lifestyle changes are key to intervening in the aging process. First, she explains that longevity medicine means optimizing the state of health of an individual before a disease occurs by antagonizing the aging processes to be healthier for longer. This focus on delaying age-related disease differentiates longevity medicine from other specialties in its proactive attempt to prolong the healthspan rather than reacting after a disease has already occurred. Dr. Maier goes on to state her goals for this specialty, including educating laypeople and medical professionals, building a credible foundation and guidelines, and accelerating research in the field. She also suggests some promising areas of research, from diagnostic clocks to the credibility of supplements, as well as discussing lifestyle changes, an intervention already known to be effective against age-related disease. Dr. Maier then discusses her involvement with the first publicly funded outpatient clinic in longevity medicine, which she’ll be opening in Singapore in 2023, and the services it will provide. Finally, Dr. Maier closes the episode with her thoughts on democratizing longevity medicine and the future of the specialty, including her hope that, within ten years, we will see a shift toward preventing and lowering age-related diseases. Episode Highlights: Quotes: “What we would like to achieve is to optimize that function at that moment in time for that individual. And optimizing function means optimizing the cognitive function but also the physical function to prevent that age-related disease.” “Nobody really knows or has really described what the effect is of these supplements over the life course and for whom. I think consumers need to know what the return on investment is of taking these kinds of supplements. On the other side, physicians should know what the possible return of investment is if these kinds of supplements are prescribed to healthy individuals if any.” “We have already interventions in place, we have diagnostics in place. And that’s the reason why I, as an internal medicine specialist, I’m opening the first longevity clinic in a publicly funded hospital because I think it’s time, and I think it’s unethical to not apply this knowledge to the population and just wait until disease occurs.” “Most importantly is that we have to give individuals the choice what they would like to achieve because if we want, as healthcare professionals, too much, and people will not stick to our recipes, nothing will happen. So it has to be a shared decision-making on what to do and what to leave out.” “We should deliver care to everybody who needs our help. And I would say helping means, in my view, to prevent age-related diseases, and thereby reduce the cost to the entire society.” Links: Email questions, comments,