Longevity Roadmap

In this episode, we are joined by Dr. Judith Frydman to explore proteostasis: the tightly regulated systems that ensure proteins are correctly folded, maintained, and cleared before they become toxic. As these systems degrade with age, misfolded proteins accumulate, cellular signaling falters, and vulnerability to neurodegeneration increases. The discussion centers on why protein folding begins du...

Over the past year, we covered a wide range of ground—from clinicians working directly with patients to top scientists studying the underlying biology of aging. This episode is a chance to look back at some of the more interesting conversations we had on Longevity Roadmap in 2025. Looking ahead, there's no sign that the pace is slowing. In longevity, it often feels like every year brings another s...

Aging is usually linked to size, metabolism, and inevitable decline—but bats defy all three. In this episode, Dr. Buck Joffrey speaks with Dr. Emma Teeling about why bats are rewriting the rules of longevity science. The discussion explores how bats live far longer than expected for their size while avoiding cancer, immune dysfunction, and chronic inflammation. They examine how stable telomeres, e...

Longevity medicine is moving beyond symptom management—and regenerative therapies are forcing a deeper look at how healing actually works. In this episode, Dr. Buck Joffrey speaks with the team at  BioXcellerator about what separates rigorous regenerative medicine from hype-driven shortcuts. The conversation focuses on why stem cells aren't about "replacing" tissue, but about directing the body's...

Aging begins when cellular quality-control systems lose their precision. In this episode, Professor Ana Maria Cuervo outlines how chaperone-mediated autophagy (CMA)—a selective lysosomal degradation pathway essential for proteostasis—progressively declines with age, triggering downstream failures across neuronal and metabolic tissues. Reduced LAMP2A availability, impaired lysosomal docking, and di...

In this episode, we are joined by Dr. Tony Wyss-Coray to discuss his groundbreaking research on brain resilience and aging. He explains how systemic factors, particularly proteins in the blood, influence cognitive function and the aging process. The discussion covers the role of proteomics, machine learning, and the potential of parabiosis and plasma infusions in developing therapies for age-relat...

In this episode, we are joined by Dr. Francisco González-Lima to delve into the metabolic mechanisms that drive brain aging and cognitive decline. He begins by outlining how reductions in cytochrome oxidase activity, disruptions in oxidative phosphorylation, and the accumulation of mitochondrial mutations progressively impair neuronal energy metabolism. These metabolic deficits, he explains, often...

We are joined by behavioral epidemiologist Dr. Kate Wolin to unpack why so many health interventions collapse outside the lab—and what actually drives lasting change in the real world. From frictionless habit design and daily self-monitoring to movement, sleep, and the muscle-preserving realities of GLP-1s, she reveals the behavioral strategies that truly move the needle on long-term metabolic and...

In this episode, we are joined by Dr. Jennifer Elisseeff to discuss the evolving field of tissue engineering and its applications in regenerative medicine. She explains the shift from using stem cells to focusing on immune cells for tissue repair, the challenges of regenerating cartilage, and the importance of vascularity in tissue health. The discussion also covers the impact of aging on tissue r...

Dr. Heidi Tissenbaum, a molecular geneticist at UMass Chan Medical School, joins Dr. Buck Joffrey to explore what C. elegans worms have revealed about the biology of aging. She explains how these simple organisms helped uncover key longevity pathways—like insulin/IGF-1 signaling and sirtuins—that also exist in humans. The conversation dives into the balance between stress and resilience, the role...

This week, Professor Jan Vijg joins us to discuss the intricate relationship between DNA mutations, epigenetic drift, and aging.  He explains the differences between mutations and epigenetic changes, the role of environmental factors, and the potential for reversing epigenetic changes. The conversation also touches on the implications of somatic mutations and the future of longevity research, part...

In this episode, we are joined by Dr. Keith Diaz to discuss the significant health risks associated with prolonged sitting, likening it to smoking in terms of its dangers. He emphasizes the importance of regular movement, introducing the concept of 'movement snacks'—short bursts of activity that can mitigate the negative effects of sitting. We also cover the physiological mechanisms behind how mov...

In this episode, we are joined by Dr. Mitchell Roslin to discuss the complexities of obesity. We explore the role of GLP-1 medications in weight management, the evolution of bariatric surgery, and the innovative SIPS procedure.   Dr. Roslin emphasizes that obesity is not merely a result of poor lifestyle choices but involves intricate biological and hormonal mechanisms.  He also highlights the imp...

In this episode, Dr. Karl Pfleger joins us to discuss the evolving landscape of longevity research and investment. He emphasizes the shift from disease-specific approaches to understanding aging as a multifaceted process that underpins many chronic diseases. Dr. Pfleger outlines his investment strategies in the aging biotech sector, highlighting the importance of addressing various sub-pathologies...

In this episode, Dr. Louise Hecker joins us to discuss her groundbreaking research on psilocybin, exploring its potential to extend cellular lifespan and improve health outcomes in aging. We delve into the mechanisms behind psilocybin's effects, findings from animal studies, and the challenges faced in conducting research on this Schedule I substance. Dr. Hecker emphasizes the importance of unders...

In this episode, Dr. Bill Andrews joins Dr. Buck Joffrey to discuss the critical role of telomeres and telomerase in aging and cellular health. He explains how telomeres shorten with each cell division, leading to aging and cellular senescence. Dr. Andrews emphasizes the importance of inducing telomerase to potentially reverse aging and shares insights from his research on telomerase inducers. He...

Dr. Derya Unutmaz joins Dr. Buck Joffrey to discuss the critical role of T cells in the immune system, their changes with aging, and the implications for chronic diseases. He emphasizes the importance of thymus regeneration and the microbiome's influence on health. The discussion also covers advancements in engineering immune cells for cancer treatment and the potential of AI in revolutionizing ag...

In this episode, Professor Peter McCaffery joins Dr. Buck Joffrey to discuss the multifaceted role of Vitamin A in brain health, particularly its function as a signaling molecule that influences neuroplasticity and cognitive functions. He elaborates on the challenges of Vitamin A supplementation, especially in aging populations, and the implications of retinoic acid signaling in neurodegenerative...

In this episode, Dave Watumull joins Dr. Buck Joffrey to discuss the benefits and mechanisms of astaxanthin, a powerful antioxidant and anti-inflammatory compound. He explains its role in longevity, particularly through the Interventions Testing Program (ITP), where astaxanthin was shown to extend lifespan in male mice by 12%. The discussion also covers the safety profile, bioavailability, and cli...

Dr. Sean Gibbons joins Dr. Buck Joffrey to discuss the complexities of the gut microbiome, its evolution, and its significant role in health and longevity. He explains how our microbiome is established at birth, how it changes throughout life, and the impact of diet and lifestyle on its composition. The discussion also covers the challenges of modifying the microbiome, the potential of precision n...

Dr. Ellie Phillips, DDS, joins Dr. Buck Joffrey to explain how oral pathogens contribute to chronic inflammation and conditions such as cardiovascular disease, Alzheimer's, and adverse pregnancy outcomes. She shares the science behind xylitol, saliva-driven remineralization, and practical strategies for supporting a healthy oral microbiome to reduce systemic risk. Learn more about Dr. Ellie Philli...

Dr. Kevin J. Tracey, neurosurgeon, immunologist, and pioneer in bioelectronic medicine, discusses the discovery of the inflammatory reflex and how vagus nerve stimulation can precisely regulate immune activity without immunosuppression. He explains its clinical application in rheumatoid arthritis, potential use in Crohn's disease, multiple sclerosis, and metabolic disorders, and its implications f...

In this conversation, Dr. Barrie Tan joins Dr. Buck Joffrey to discuss the significance of tocotrienols—a lesser-known form of vitamin E—and their potential role in preventing chronic disease and promoting healthy aging. Dr. Tan explains the differences between tocopherols and tocotrienols, the role of vitamin E in human health, and highlights the annatto plant as a key natural source of tocotrien...

Joining Dr. Buck Joffrey this week, Dr. Bobby Mukkamala shares his journey from aspiring cardiothoracic surgeon to becoming the president of the American Medical Association. He discusses his personal health challenges, including a brain tumor diagnosis, and how it has shaped his perspective on healthcare. The conversation delves into the importance of preventative medicine, the impact of the Flin...

In this conversation, Dr. Buck Joffrey and Dr. Steven Austad discusse the biology of aging, the evolutionary aspects of longevity, and the potential for genetic technologies to extend human health span. Dr. Austad emphasizes the complexity of aging, the importance of glucose control, and the need for further research into species that exhibit remarkable longevity. The discussion also touches on th...