In this episode of Levity, host sits down with Dr. Rochelle Buffenstein, the world’s leading expert on naked mole-rats—bizarre, long-lived rodents that appear to defy aging. With over 200 scientific publications and decades of research, Dr. Buffenstein shares how these animals resist cancer, maintain fertility, and show no increase in mortality with age. The conversation explores what makes naked mole-rats such powerful models for understanding longevity and what their biology might teach us about healthy aging.

Key Points:

Naked mole-rats challenge everything we know about aging, living over 40 years without typical signs of decline. Their resistance to cancer, unique immune system, and extreme environmental adaptations offer a blueprint for longevity. Studying them could unlock transformative insights into how humans might slow or even prevent age-related diseases.

• Aging Resistance & Longevity: Naked mole-rats live over 40 years—up to ten times longer than expected for their size—and do not exhibit the typical increase in mortality or physiological decline with age. Unlike other mammals, they maintain tissue health, fertility, and resilience across decades.
• Mastery of Aging Hallmarks: They show resistance to nearly all cellular hallmarks of aging, including preserved telomeres, enhanced protein maintenance (proteostasis), minimal senescence, and robust stress responses, all contributing to their healthy, extended lifespan.
• Cancer Resistance: Despite decades of observation and thousands of autopsies, only a handful of mole-rats have developed cancer. Their tissues secrete high-molecular-weight hyaluronan and maintain tight cellular control, potentially preventing tumor formation and spread.
• Brain & Cognitive Health: Even aged mole-rats display no signs of neurodegenerative disease. They maintain high levels of tau and beta-amyloid proteins without developing plaques or tangles, possibly due to superior protein regulation and ongoing adult neurogenesis.
• Unique Immune System: Unlike most mammals, they rely heavily on innate immunity, with an abundance of macrophages and neutrophils. They also lack natural killer cells yet remain resilient to cancer and infections—likely due to their subterranean, pathogen-free habitat.
• Eusocial Life & Reproductive Skew: Colonies feature a single breeding queen and hundreds of non-breeding subordinates. Dominant females suppress reproduction in others through aggression. Interestingly, any female—regardless of age—can become a queen if separated from the colony.
• Adaptations to Harsh Environments: They survive extreme hypoxia and high CO₂ thanks to metabolic flexibility (e.g., fructose-driven glycolysis), fetal-like heart proteins, and remarkable resilience to acidosis. Their thermoregulation is finely tuned, aided by large stores of brown fat.
• Translational Potential & Research Gap: Although mole-rats offer immense insight into healthy aging, they remain underused in research due to maintenance costs and unconventional biology. Dr. Rochelle Buffenstein advocates expanding funding and model systems to unlock new therapies.