Inducing a Torpor-Like State in Mice Slows Aging
Torpor is characteristic of hibernating mammals, involving reduced body temperature and slowed metabolism. Researchers have discovered a way to induce this state in mice, and demonstrate that implementing a schedule of intermittent repeated periods of torpor produces an extension of healthspan. This ties in to an established literature on the relationships between metabolic rate, body temperature, and lifespan in mammals, in that one would expect reduced body temperature to produce a modest slowing of aging.
Torpor is a state of profoundly decreased metabolic rate, driving a decrease in core body temperature that can last from hours to days, whereas hibernation is a seasonal behavior comprising multiple bouts of torpor interrupted by periodic arousals to euthermia. These extraordinary adaptations raise many unanswered fundamental questions of homeotherm biology, one of the most compelling being the link between torpor and longevity. Natural torpor is characterized by tightly coupled, extreme physiological changes that have been individually implicated in aging and longevity, such as decreased core body temperature and metabolic rate, and caloric restriction. Indeed, hibernating species exhibiting long torpor bouts show extended longevity compared to closely related non-hibernators and longer lifespan than would be expected based on body mass alone.
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 on blood epigenetic aging and find that the decelerating effect of the TLS on aging is mediated by decreased body temperature. 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 body temperature is an important mediator of the aging processes.