2. Academic Validation
  3. Systemic induction of senescence in young mice after single heterochronic blood exchange

Systemic induction of senescence in young mice after single heterochronic blood exchange

  • Nat Metab. 2022 Aug;4(8):995-1006. doi: 10.1038/s42255-022-00609-6.
Ok Hee Jeon 1 2,  Melod Mehdipour 3,  Tae-Hwan Gil 4,  Minha Kang 4,  Nicholas W Aguirre 5,  Zachery R Robinson 3,  Cameron Kato 3,  Jessy Etienne 3,  Hyo Gyeong Lee 4,  Fatouma Alimirah 5,  Vighnesh Walavalkar 6,  Pierre-Yves Desprez 5,  Michael J Conboy 3,  Judith Campisi 7 8,  Irina M Conboy 9
Affiliations

Affiliations

  • 1 Buck Institute for Research on Aging, Novato, CA, USA. [email protected].
  • 2 Department of Biomedical Sciences, Korea University College of Medicine, Seoul, Republic of Korea. [email protected].
  • 3 Department of Bioengineering and QB3 Institute, University of California, Berkeley, CA, USA.
  • 4 Department of Biomedical Sciences, Korea University College of Medicine, Seoul, Republic of Korea.
  • 5 Buck Institute for Research on Aging, Novato, CA, USA.
  • 6 Surgical Pathology, University of California, San Francisco, CA, USA.
  • 7 Buck Institute for Research on Aging, Novato, CA, USA. [email protected].
  • 8 Lawrence Berkeley National Laboratory, Berkeley, CA, USA. [email protected].
  • 9 Department of Bioengineering and QB3 Institute, University of California, Berkeley, CA, USA. [email protected].
PMID: 35902645 DOI: 10.1038/s42255-022-00609-6
Abstract

Ageing is the largest risk factor for many chronic diseases. Studies of heterochronic parabiosis, substantiated by blood exchange and old plasma dilution, show that old-age-related factors are systemically propagated and have pro-geronic effects in young mice. However, the underlying mechanisms how bloodborne factors promote ageing remain largely unknown. Here, using heterochronic blood exchange in male mice, we show that aged mouse blood induces cell and tissue senescence in young Animals after one single exchange. This induction of senescence is abrogated if old Animals are treated with senolytic drugs before blood exchange, therefore attenuating the pro-geronic influence of old blood on young mice. Hence, cellular senescence is neither simply a response to stress and damage that increases with age, nor a chronological cell-intrinsic phenomenon. Instead, senescence quickly and robustly spreads to young mice from old blood. Clearing senescence cells that accumulate with age rejuvenates old circulating blood and improves the health of multiple tissues.

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