In this year-end episode, host Buck Joffrey revisits the most striking ideas and debates from Longevity Roadmap in 2025, drawing on conversations with clinicians and basic scientists. The discussion spans mitochondria, diet, muscle, immune aging, and emerging anti-aging therapies, while looking ahead to what 2026 may bring.

Key Points:

This “Best of 2025” episode paints aging as a systems problem rooted in metabolism, immunity, and lifestyle. While drugs like rapamycin and AI-guided therapies show promise, foundational factors—diet quality, muscle strength, mitochondrial health, and sunlight-driven hormones—remain critical. The message is clear: longevity isn’t a single pill, but a careful balance of biology, behaviour, and emerging science.

• Aging biology & AI-driven therapies: Rapid advances in AI and network-based drug repurposing are accelerating the search for interventions that target the hallmarks of aging, with early clinical readouts expected soon.
• Mitochondria at the centre of aging: Metabolic dysfunction is framed as mitochondrial inefficiency—tiny drops in energy conversion can cascade into obesity, diabetes, cancer, dementia, and other chronic diseases.
• Ultra-processed foods & metabolic damage: NOVA class 4 foods strongly predict chronic disease, driven by excess sugar, lack of fibre and omega-3s, and emulsifiers that damage the gut lining and fuel systemic inflammation.
• Immunity, thymus, and trade-offs: The thymus is presented as a master regulator of immune aging; while growth hormone can regenerate it, adverse effects on insulin sensitivity highlight the complexity of anti-aging trade-offs.
• Muscle, nutrition, and lifestyle matter: Muscle strength emerges as one of the strongest predictors of longevity, outperforming many biomarkers, reinforcing the importance of resistance training alongside diet and metabolic health.