A torpor-like state (TLS) in mice slows blood epigenetic aging and prolongs healthspan.

Autor: Jayne L; Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, 455 Main Street, Cambridge, MA 02142, USA.; Department of Neurobiology, Harvard Medical School, Boston, MA 02115.; Present address: Department of Neurobiology, Stanford University Medical Center, Stanford, CA, USA., Lavin-Peter A; Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, 455 Main Street, Cambridge, MA 02142, USA.; Department of Neurobiology, Harvard Medical School, Boston, MA 02115., Roessler J; Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, 455 Main Street, Cambridge, MA 02142, USA., Tyshkovskiy A; Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA., Antoszewski M; Division of Hematology/Oncology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Ren E; Department of Neurobiology, Harvard Medical School, Boston, MA 02115., Markovski A; Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, 455 Main Street, Cambridge, MA 02142, USA., Sun S; Department of Neurobiology, Harvard Medical School, Boston, MA 02115.; Program in Neuroscience, Harvard Medical School, Boston, MA, USA., Yao H; Department of Neurobiology, Harvard Medical School, Boston, MA 02115., Sankaran VG; Division of Hematology/Oncology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Gladyshev VN; Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.; Broad Institute of MIT and Harvard, Cambridge, MA, USA., Brooke RT; Epigenetic Clock Development Foundation, Torrance, CA, USA., Horvath S; Epigenetic Clock Development Foundation, Torrance, CA, USA.; Altos Labs, Cambridge, UK., Griffith EC; Department of Neurobiology, Harvard Medical School, Boston, MA 02115., Hrvatin S; Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, 455 Main Street, Cambridge, MA 02142, USA.
Jazyk: angličtina
Zdroj: BioRxiv : the preprint server for biology [bioRxiv] 2024 Mar 25. Date of Electronic Publication: 2024 Mar 25.
DOI: 10.1101/2024.03.20.585828
Abstrakt: 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 health span, remain unknown. We demonstrate that the activity of a spatially defined neuronal population in the avMLPA, 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 health span. We isolate the effects of decreased metabolic rate, long-term caloric restriction, and decreased core body temperature (T b ) on blood epigenetic aging and find that the pro-longevity effect of torpor-like states is mediated by decreased T b . Taken together, our findings provide novel mechanistic insight into the pro-longevity effects of torpor and hibernation and support the growing body of evidence that T b is an important mediator of aging processes.
Competing Interests: Competing Interests S. Horvath and R.T. Brooke are founders of the non-profit Epigenetic Clock Development Foundation, which licenses several patents from UC Regents including a patent on the mammalian methylation array platform. These patents list S.Horvath as inventor. V.G.S. serves as an advisor to and/or has equity in Branch Biosciences, Ensoma, and Cellarity, all unrelated to this work.
Databáze: MEDLINE
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