Inducing hibernation can significantly delay aging and prolong healthy life
In response to food scarcity or harsh environmental conditions, many mammals adopt energy-conservation strategies such as hibernation and hibernation.
Hibernation is a state in which the metabolic rate drops dramatically, resulting in a drop in core body temperature (Tb) that can last from hours to days.
Hibernation, on the other hand, is a seasonal behavior consisting of multiple hibernation states, interrupted by periodic awakenings of normal body temperature.
Both hibernation and hibernation are associated with longevity effects.
It is not clear how hibernation affects aging and whether it can slow aging and extend healthy life by inducing hypothermia and a low metabolic state.
On March 7, 2025, The team of Professor Sinisa Hrvatin from MIT's Whitehead Institute for Biomedical Research published A paper in the journal Nature Aging entitled "A torpor-like state in mice slows blood epigenetic aging and Aging. prolongs healthspan "article.
The study mimics natural hibernation patterns by inducing a prolonged state of "hibernation" (TLS) and found that TLS significantly improved clinical indicators of age-related frailty in mice and slowed epigenetic aging in a tissue-specific manner.
Notably, TLS had the greatest effect on epigenetic aging in the blood, slowing epigenetic aging by 76% in a single mouse.
The researchers first injected AAV-hSyn-hM3D (Gq)-mCherry into the anterior and ventral parts of the medial and lateral preoptic areas (avMLPA) of the hypothalamus, Subsequent intraperitoneal injection of Gq-DREADD activates the synthetic ligand clozapine-n-oxide (CNO) to activate neurons within avMLPA, resulting in a reduction in Tb, as observed during natural faster-induced hibernational episodes.
The researchers then repeatedly administered CNO to induce TLS to mimic natural hibernation patterns, leading to TLS flare-ups and periodic body temperature awakenings.
After 3 months, by analyzing the epigenetic ages of blood, liver, kidney, and cortex, it was found that the average blood aging rate of mice in the TLS group was 80% lower than that of age-matched controls, and the average liver aging rate was 20% lower.
These data suggest that inducing TLS in facultative heterothermals that cannot hibernate naturally can reproduce the effects of natural hibernation on blood epigenetic aging.
To better investigate the effects of TLS on epigenetic aging and age-related decline in physiological function, the researchers continuously measured the blood epigenetic ages of mice 0, 3, 6, and 9 months after induction of TLS.
The results showed that after 9 months of TLS induction, mice in the TLS group were about 3.0 ± 0.6 months younger than control mice, and linear regression analysis found that 9 months of TLS induction reduced the rate of blood epigenetic aging by 36.9%.
After 9 months of TLS induction, the experimental group of mice scored significantly lower on the frailty index assessment than the age-matched control group, indicating a significantly improved healthy lifespan and younger physiological function.
AThe researchers explored the effects of reduced metabolic rate, long-term caloric restriction, and reduced core body temperature (Tb) on blood epigenetic aging and found that the ameliorative effects of TLS on aging are mediated by Tb reduction.
AThese results provide new mechanistic insights into the slowing effects of hibernation and hibernation on aging and suggest that Tb is an important mediator in the aging process.
AReference: https://www.nature.com/articles/s43587-025-00830-4
