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 during translation, how molecular chaperones like TRIC preserve cellular integrity, and why aging creates a self-reinforcing cycle of proteostatic failure.

We also examine upstream mechanisms—and what restoring proteostasis could mean for future longevity interventions, healthspan preservation, and disease prevention.

Watch the full episode to understand why protein folding may be one of the most underappreciated levers in aging biology.

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 set of breakthroughs, and 2026 is shaping up to be a big one. One of the most important trends to watch is the increasing role of artificial intelligence in medicine, particularly in pharmaceuticals. AI-driven, network-based drug repurposing efforts are starting to identify compounds that may influence aging biology and move more efficiently toward clinically relevant interventions. By the end of 2026, it's reasonable to expect early readouts or expanded trials that begin to meaningfully target the hallmarks of aging.

Before wrapping up this year, I just want to say thanks to everyone who's been listening this year. Your interest, your feedback, and your willingness to think critically about this space are what make the show worth doing.

See you in 2026!

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Download Dr. Buck Joffrey's FREE ebook, Living Longer for Busy People: https://ru01tne2.pages.infusionsoft.net/?affiliate=0

Book a FREE longevity coaching consultation with Dr. Buck Joffrey: https://coaching.longevityroadmap.com

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, enhanced DNA repair, and tightly controlled immune responses allow bats to age slowly despite extreme metabolic demands.

Watch the full episode to understand why bat biology is reshaping how researchers think about human aging and healthspan.

Learn more about Dr. Emma Teeling:

https://people.ucd.ie/emma.teeling

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Download Dr. Buck Joffrey's FREE ebook, Living Longer for Busy People: https://ru01tne2.pages.infusionsoft.net/?affiliate=0

Book a FREE longevity coaching consultation with Dr. Buck Joffrey: https://coaching.longevityroadmap.com

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 own repair systems through immune signaling, inflammation control, and cellular communication. Drawing from Buck's own experience receiving treatment at BioXcellerator, the discussion unpacks why cell source, processing, viability, and delivery fundamentally shape outcomes.

They break down the differences between Wharton's jelly–derived mesenchymal stem cells and adult autologous cells, how hypoxic culturing alters therapeutic signaling, and why exosomes alone are not interchangeable with living cells.

They also address the regulatory gray zones surrounding regenerative medicine and why high-quality real-world data matters in a field driven by complex biology.

Watch the full episode to understand how regenerative medicine actually works—and where it's headed.

Learn more about BioXcellerator:

https://www.bioxcellerator.com/

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Download Dr. Buck Joffrey's FREE ebook, Living Longer for Busy People: https://ru01tne2.pages.infusionsoft.net/?affiliate=0

Book a FREE longevity coaching consultation with Dr. Buck Joffrey: https://coaching.longevityroadmap.com

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 disrupted protein triage lead to toxic proteotoxic burden, mitochondrial dysfunction, and metabolic inflexibility.

Emerging evidence shows that preserving CMA activity can improve healthspan, attenuate neurodegenerative pathology, and restore metabolic homeostasis.

Learn more about Dr. Ana Maria Cuervo:

https://einsteinmed.edu/faculty/8784/ana-maria-cuervo

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-related diseases like Alzheimer's.

Dr. Wyss-Coray emphasizes the importance of understanding the biological markers of aging and resilience to create targeted interventions for healthier aging.

Learn more about Dr. Wyss-Coray:

https://brainresilience.stanford.edu/

https://www.verobioscience.com/

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Download Dr. Buck Joffrey's FREE ebook, Living Longer for Busy People: https://ru01tne2.pages.infusionsoft.net/?affiliate=0

Book a FREE longevity coaching consultation with Dr. Buck Joffrey: https://coaching.longevityroadmap.com

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 emerge long before the structural abnormalities associated with Alzheimer's disease.

Building on this foundation, the conversation examines how reactive oxygen species, mitochondrial inefficiency, and altered cortical oxygen utilization contribute to diminished cognitive resilience over time. Dr. González-Lima highlights why these metabolic disturbances provide a more coherent explanation for geriatric dementia than traditional protein-centric models.

The discussion then shifts to emerging therapeutic strategies. Dr. González-Lima reviews evidence for low-dose methylene blue and 1064 nm transcranial photobiomodulation, both of which appear to enhance mitochondrial respiration and support prefrontal function by directly targeting cytochrome oxidase activity.

He concludes by emphasizing the need for metabolism-focused interventions, improved cerebral perfusion, and more precise energy-based frameworks to guide the future of brain-aging therapeutics.

Learn more about Dr. Francisco González-Lima: https://liberalarts.utexas.edu/psychology/faculty/fg

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Download Dr. Buck Joffrey's FREE ebook, Living Longer for Busy People: https://ru01tne2.pages.infusionsoft.net/?affiliate=0

Book a FREE longevity coaching consultation with Dr. Buck Joffrey: https://coaching.longevityroadmap.com

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 overall health.

Watch the full episode to learn how evidence-based behavior science can transform your healthspan.

Learn more about Dr. Kate Wolin:

https://drkatewolin.com/

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Download Dr. Buck Joffrey's FREE ebook, Living Longer for Busy People: https://ru01tne2.pages.infusionsoft.net/?affiliate=0

Book a FREE longevity coaching consultation with Dr. Buck Joffrey: https://coaching.longevityroadmap.com

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 repair, the role of senescent cells, and the future of personalized medicine in tissue engineering.

Dr. Elisseeff emphasizes the need for innovative approaches and the integration of immunotherapies to enhance tissue repair processes.

Learn more about Dr. Jennifer Elisseeff:

https://www.bme.jhu.edu/people/faculty/jennifer-h-elisseeff/

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Download Dr. Buck Joffrey's FREE ebook, Living Longer for Busy People: https://ru01tne2.pages.infusionsoft.net/?affiliate=0

Book a FREE longevity coaching consultation with Dr. Buck Joffrey: https://coaching.longevityroadmap.com

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 of IGF-1 in muscle health and lifespan, and why she believes true longevity breakthroughs will require understanding how the body's systems communicate as a whole.

Learn more about Dr. Heidi Tissenbaum:

https://profiles.umassmed.edu/display/133231

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Download Dr. Buck Joffrey's FREE ebook, Living Longer for Busy People: https://ru01tne2.pages.infusionsoft.net/?affiliate=0

Book a FREE longevity coaching consultation with Dr. Buck Joffrey: https://coaching.longevityroadmap.com