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

Ok Hee Jeon, Melod Mehdipour, Tae Hwan Gil, Minha Kang, Nicholas W. Aguirre, Zachery R. Robinson, Cameron Kato, Jessy Etienne, Hyo Gyeong Lee, Fatouma Alimirah, Vighnesh Walavalkar, Pierre Yves Desprez, Michael J. Conboy, Judith Campisi, Irina M. Conboy

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)995-1006
Number of pages12
JournalNature Metabolism
Volume4
Issue number8
DOIs
Publication statusPublished - 2022 Aug

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Physiology (medical)
  • Cell Biology

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