Insights from Animal Anti-Aging Mechanisms for Human Aging Therapy

Senescence is a ubiquitous but highly variable process that occurs in a variety of species, from short-lived rodents to centuries-long whales and clams. Comparative biology provides important insights into the molecular and cellular adaptations behind longevity. While humans face age-related genomic instability, telomere wear, mitochondrial dysfunction, and stem cell depletion, long-lived species such as whales, birds, naked mole rats, bats, and Greenland sharks exhibit unique adaptations that can mitigate these processes. These natural experiments shed light on therapeutic pathways to extend human healthspan, including anti-aging drugs, telomere therapy, epigenetic reprogramming, and caloric restriction mimics. This article reviews the characteristics of aging, explores the mechanisms of longevity at a very large scale, and evaluates their translational potential in human medicine. Combining evolutionary perspectives with biomedical research, it also reviews the common and differentiating mechanisms of aging across species and highlights how unique biological solutions can inspire innovative interventions in human medicine. We believe that combining evolutionary biology with clinical translation has the potential to fundamentally reshape the paradigm of aging research, providing a roadmap for advancing progress from disease management to staying alive throughout the human lifecycle and integrating evolutionary insights into biomedical research has the potential to fundamentally shift medicine from disease treatment to aging prevention.