By Nature Aging –
Torpor and hibernation are extreme physiological adaptations of homeotherms associated with pro-longevity effects. Yet the underlying mechanisms of how torpor affects aging, and whether hypothermic and hypometabolic states can be induced to slow aging and increase healthspan, remain unknown. Here we demonstrate that the activity of a spatially defined neuronal population in the preoptic area, which has previously been identified as a torpor-regulating brain region, is sufficient to induce a torpor-like state (TLS) in mice. Prolonged induction of TLS slows epigenetic aging across multiple tissues and improves healthspan. We isolate the effects of decreased metabolic rate, long-term caloric restriction, and decreased core body temperature (Tb) on blood epigenetic aging and find that the decelerating effect of TLSs on aging is mediated by decreased Tb. Taken together, our findings provide novel mechanistic insight into the decelerating effects of torpor and hibernation on aging and support the growing body of evidence that Tb is an important mediator of the aging processes…
To examine the effects of TLS on aging, we induce prolonged TLS to model a natural hibernation-like pattern over the course of months and find that TLS improved clinical measures of age-associated frailty in mice and slowed epigenetic aging in a tissue-specific manner. TLS had the greatest effect on epigenetic aging in the blood, where it slowed epigenetic aging by up to 76% in individual mice. Moreover, we leverage the uniquely controllable nature of our model to elucidate the underlying mechanisms of the decelerating effect of TLS on blood epigenetic aging, demonstrating that this effect is not mediated by caloric restriction nor decreased metabolic rate but rather stems from a decrease in Tb.
