Translating Aging

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

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

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

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

Dr. Carolina Reis Oliveira and Dr. Alessandra Zonari, co-founders of OneSkin, discuss how they are using recent advances in longevity science to create peptides that target senescent cells and inflammation in aged skin. They explain their rigorous discovery process, testing lead peptide OS-1 in 3D skin models and human trials, and validating safety and efficacy to meet regulatory requirements. They also share insights into launching a science-backed skincare brand and ongoing R&D for new applications.

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

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

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:How Ora Biomedical was founded out of a conversation between Dr. Lee and his mentor Dr. Matt Kaeberlein about spinning out a company based on the WormBot technologyWhy C. elegans is a useful model organism for discovering fundamental mechanisms of aging that can translate to mammalsHow the WormBot platform uses imaging and machine learning to measure worm lifespan, healthspan, behaviors, and response to drugs at a large scaleOra's goal of screening 1 million compounds within 3 years to find the most promising longevity interventionsStrategies for translating hits from the worm screen into rare disease therapies and direct-to-consumer natural productsThe promise of longevity interventions discovered through unbiased phenotypic screening to prevent age-related diseases and transform human healthQuotes: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.comTranslating Aging on Twitter: @bioagepodcastBioAge Labs Website bioagelabs.comBioAge Labs Twitter @bioagelabsBioAge Labs LinkedInOra 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: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

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.OutlineThe Time Initiative’s mission to inspire and cultivate future leaders in aging biology by supporting undergraduatesThe need to expand the talent pool and workforce to drive progress in aging researchThe potential of geroscience and rejuvenation biotech to transform human health and societyCollaborative efforts with the American Federation for Aging Research (AFAR) Events, resources, and opportunities available through The Time Initiative to educate students about aging researchThe Time Fellowship program: Open to all disciplines All-expenses paid annual retreat Community group and mentorship opportunities$8,000 grants for summer projectsComparing The Time Initiative to similar organizations also focused on community building in longevity scienceAdvice and resources for students interested in aging research and geroscienceA vision for The Time Initiative’s growth and future impact on the fieldQuotes:“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. Educate yourself, build your network, and believe in your potential.""Enabling future leaders in aging is about more than just providing them with knowledge and skills. It's about instilling them with a sense of purpose and a desire to make a difference."“I'm constantly fighting against underestimating my capacity for impact. But in learning to let go of that all of these really incredible opportunities have come my way. And it's really made room for me to just continually grow and learn.”“I envision a future where our fellows are empowered by this experience through our program, and they become influential figures in the field. I'm really excited about the future and the roles that the Time Initiative and our fellows will play in shaping it.”Links: Email questions, comments, and feedback to podcast@bioagelabs.comTranslating Aging on Twitter: @bioagepodcastBIOAGE Labs Website BIOAGELabs.comBIOAGE Labs Twitter @bioagelabsBIOAGE Labs LinkedInTime Initiative