Translating Aging

Latest Episodes:

Hevolution: Extending Global Healthspan (Dr. Mehmood Khan, CEO) Jul 17, 2024

Show notes

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 mission
The importance of aging research in the context of global challenges
Hevolution's collaborative approach and funding strategies
Challenges in translating aging research into accessible interventions
The need for validated biomarkers in aging research
Global perspectives on aging, including challenges in developing countries
The importance of policy engagement and public awareness in advancing the field

https://www.hevolution.com/

Harnessing the Secretome to Combat Age-Related Immune Dysfunction (Dr. Hans Keirstead, Immunis) May 08, 2024

Show notes

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 DETAILS

The critical role of the immune system in the aging process and age-related disease
Immunis' focus on immune precursor cell secretome factors to restore youthful immune function
Preclinical studies demonstrating the effects of Immunis' secretome product on muscle growth, metabolism, and inflammation in aged mice
Early results from Immunis' Phase 1/2a clinical trial in older adults with muscle atrophy and knee osteoarthritis
The potential for immune secretome therapeutics to treat a wide range of age-related conditions and enhance healthspan
The importance of developing affordable and accessible therapies to maximize impact

QUOTES

"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 PAPER

Stem cell secretome treatment improves whole-body metabolism, reduces adiposity, and promotes skeletal muscle function in aged mice

Delaying menopause, extending healthspan: The promise of AMH-based therapeutics (Daisy Robinton, Oviva Therapeutics) Apr 03, 2024

Show notes

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 startup
Ovaries as central regulators of female healthspan beyond reproduction
AMH as a brake on follicle activation and loss of ovarian reserve
Using enhanced AMH to improve egg yield in poor-responding IVF patients
Potential of AMH-based therapy to delay menopause and slow aging
Menopause as the single greatest known accelerator of aging
Economic and societal impact of extending female healthspan
Distinguishing reproductive longevity from overall women's health
Viewing fertility as a marker of overall health and wellbeing

Gene Therapies to Treat and Reverse Aging (Noah Davidsohn, Rejuvenate Bio) Mar 20, 2024

Show notes

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 disease
Lifespan doubling in old mice with cyclic Yamanaka factor induction
Controllable gene therapy system for in vivo partial reprogramming
Choice of FGF-21 for pleiotropic effects deliverable from liver
Lead programs for arrhythmogenic cardiomyopathy and mitral valve disease
Advantages of treating age-related diseases first in dogs
Combination gene therapy for osteoarthritis: TGF-beta and klotho
Secreted proteins enable broad effects without broad delivery
Vision of expanding healthspan by "squaring the curve"
Potential to keep people healthy, active and productive to 100+

30 Years of Aging Biology: A Pioneer's Perspective (Cynthia Kenyon, VP-Aging Research at Calico Labs) Dec 06, 2023

Show notes

30 Years of Aging Biology: A Pioneer’s Perspective (Cynthia Kenyon - VP Aging Biology, Calico Labs)

Dr. Cynthia Kenyon reflects on the evolution of the longevity field over the 30 years since the publication of her groundbreaking paper, “A C. elegans mutant that lives twice as long as wild type,” a genetic analysis of one of the first single-gene mutations to extend lifespan in the worm. She recounts the initial excitement and skepticism around the idea of a pathway that regulates aging, and subsequent validation of this and related ideas in a wide range of model organisms. She also discusses her longstanding belief in the translational potential to improve human healthspan, and her experience as a co-founder of one of the first longevity biotech startups, Elixir Pharmaceuticals, in 1999. Based on her unique historical perspective—and with undiminished enthusiasm—she looks ahead to the unsolved mysteries that will propel the next generation of breakthroughs.

Key ideas:

Origins of looking at aging regulation in C. elegans in the 1990s
age-1 and daf-2 as the first aging genes
Early resistance to the idea of studying aging at the molecular level
Cloning of genes to reveal conserved longevity pathways (IIS/mTOR)
Extending lifespan in invertebrates, and then mice
The connection between stress resistance to evolutionary theory
Dr. Kenyon's initial belief in the translatability of aging science
Co-founding Elixir Pharmaceuticals in 1999 to target aging
Current optimism about interventions against aging
Need for public funding of large trials of natural compounds
Excitement about newest mechanisms like reprogramming
The enduring promise of targeting core nutrient-sensing networks
Developmental origins of aging rates and resilience

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

XPRIZE Healthspan: Catalyzing Therapies for Aging (Jamie Justice, PhD) Nov 29, 2023

Show notes

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 attention
The role and track record of incentive competitions like XPRIZE
Motivation and sponsors enabling XPRIZE Healthspan ($101M purse)
Timeline from conceptualization to upcoming 7-year active competition
Expert endpoint committee setting measurable functional criteria
Initial public commentary period for radical collaboration with teams
Phases: Intent to compete, qualifying submissions, finalist selection
Existing prevention trials can add program assessments
Common data and protocols to validate findings across teams
Goal of demonstrating restoration of function across domains
Secondary judging criteria around accessibility, biomarkers
Driving global coordination, investment, and innovation

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

"How We Age: The Science of Longevity" (Professor Coleen Murphy, Princeton) Nov 01, 2023

Show notes

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 longevity
Defining aging conceptually and how metrics like lifespan vs. healthspan are measured
Using genetics, transcriptomics and other tools to understand molecular changes in aging
The prominent role of reproduction and sex differences in aging
Theories on tradeoffs between reproduction and longevity
Genetics of aging pathways including insulin/IGF-1, mTOR, and sirtuins
Cellular processes involved in aging such as mitochondrial dysfunction, epigenetic changes, senescence
The importance of models like C. elegans and Drosophila in aging research
Ongoing research and future potential for interventions to increase healthspan
The challenge of complex science without excessive jargon
Highlighting critical contributions by women scientists in the field
Omitting personal lifestyle advice and focusing on evidence-based science
The rapid pace of advancement in biotech applications of longevity science

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

From Startup to Acquisition (Nick Hertz, Mitokinin) Oct 11, 2023

Show notes

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 mitochondria
Founding a company based on academic research and discoveries
Navigating from tool compounds to optimizing in vivo activity and drug properties
Using mitochondrial biomarkers like phospho-ubiquitin to track target engagement
Partnering with AbbVie: alignment on science, IP transfer after acquisition
Importance of reproducibility, following the science to clinic-ready agents
Planning the next neurodegeneration startup based on past experience
Advice for startups: pick projects wisely, focus on robust science over hype

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

Catalyzing moonshots in longevity biotech (Alex Colville, Age1) Sep 27, 2023

Show notes

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 vision
Alex's path from aging researcher to VC investor and community builder
How VCs raise funds from different types of investors (LPs)
Age1's focus on early-stage companies and contrarian, ambitious founders
Sourcing and identifying high-potential founders through networks and events
The importance of founder motivation and pragmatism in Age1's investments
Age1's first investment in Aperture Therapeutics targeting neuroinflammation
Unique value-add Age1 provides with specialized aging expertise
Empowering founders by showing people "like them" can build startups
Age1's moonshot goal of enabling agency over healthspan and lifespan

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

Reversing Skin Aging at the Cellular Level (Carolina Reis Oliveira and Alessandra Zonari, OneSkin) Aug 23, 2023

Show notes

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 aging
The cellular and molecular changes underlying skin aging
How most skincare products focus on temporary effects vs. targeting root causes
Screening peptide libraries in cellular models to discover senolytic/senomorphic candidates
Discovery and testing of lead peptide OS-1 in 3D skin models and human trials
Validating safety and efficacy to meet cosmetics regulatory requirements
Launching a science-backed skincare brand and resonating with educated consumers
Ongoing R&D to expand into new anti-aging applications and delivery methods

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

Nature Aging paper