A torpor-like state in mice slows blood epigenetic aging and prolongs healthspan
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 (T<sub>b</sub>) on blood epigenetic aging and find that the decelerating effect of TLSs on aging is mediated by decreased T<sub>b</sub>. 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 T<sub>b</sub> is an important mediator of the aging processes.
Authors
- Senmiao Sun (ORCID: https://orcid.org/0000-0002-5188-4374)
- Steve Horvath (ORCID: https://orcid.org/0000-0002-4110-3589)
- Vijay G. Sankaran (ORCID: https://orcid.org/0000-0003-0044-443X)
- Alexander Tyshkovskiy (ORCID: https://orcid.org/0000-0002-6215-190X)
- Vadim N. Gladyshev (ORCID: https://orcid.org/0000-0002-0372-7016)
- Mateusz Antoszewski (ORCID: https://orcid.org/0000-0002-7651-0547)
- Hanqi Yao (ORCID: https://orcid.org/0000-0002-7038-7525)
- Robert T. Brooke (ORCID: https://orcid.org/0000-0001-8492-5198)
- Aleksandar Markovski (ORCID: https://orcid.org/0000-0002-2065-5210)
- Julian Roessler (ORCID: https://orcid.org/0000-0003-1893-5720)
- Aurora Lavin-Peter
- Siniša Hrvatin (ORCID: https://orcid.org/0000-0001-7303-4218)
- Lorna Jayne
- Erika Ren (ORCID: https://orcid.org/0009-0009-7861-1139)
- Eric C. Griffith (ORCID: https://orcid.org/0000-0003-0428-3215)
Institutions
- Broad Institute (US)
- Brigham and Women's Hospital (US)
- Boston Children's Hospital (US)
- Harvard University (US)
- Dana-Farber Cancer Institute (US)
- Stanford Medicine (US)
- Whitehead Institute for Biomedical Research (US)
- Massachusetts Institute of Technology (US)
- Stanford University (US)
Publication Details
- Journal
- Nature Aging
- Published
- 2025-03-07
- DOI
- https://doi.org/10.1038/s43587-025-00830-4
- Citations
- 13
- Primary Topic
- Dietary Effects on Health
- Type
- article
- Field-Weighted Citation Impact
- 15.14