TY - JOUR
T1 - Systemic induction of senescence in young mice after single heterochronic blood exchange
AU - Jeon, Ok Hee
AU - Mehdipour, Melod
AU - Gil, Tae Hwan
AU - Kang, Minha
AU - Aguirre, Nicholas W.
AU - Robinson, Zachery R.
AU - Kato, Cameron
AU - Etienne, Jessy
AU - Lee, Hyo Gyeong
AU - Alimirah, Fatouma
AU - Walavalkar, Vighnesh
AU - Desprez, Pierre Yves
AU - Conboy, Michael J.
AU - Campisi, Judith
AU - Conboy, Irina M.
N1 - Funding Information:
We thank I. Silverstein for help with blood exchange procedures and T. Rando and a subaward from the Glenn Foundation for Medical Research for funding our early background work. This work was supported by a postdoctoral fellowship from the Glenn Foundation for Medical Research, Korea University grant nos. K2006261 and K2025261; the National Research Foundation of Korea Government grant nos. NRF 2020R1C1C1009921 (O.H.J.) and NIH T32 AG002266 (N.W.A.); the Pew Charitable Trust awarded to the Buck Institute for Research on Aging; by grants from the NIH nos. P01 AG017242 and R01 AG051729 (J.C.); grant nos. NIH 1R01AG071787, R56 AG058819, R01 EB023776, R01 HL139605, and the Open Philanthropy Foundation and the QB3 Calico Award (I.M.C.). A collaborative grant no. R56 AG052988 SA23061 (J.C. and I.M.C.) greatly aided these studies. Schematics of all experimental designs were created with BioRender.com.
Funding Information:
We thank I. Silverstein for help with blood exchange procedures and T. Rando and a subaward from the Glenn Foundation for Medical Research for funding our early background work. This work was supported by a postdoctoral fellowship from the Glenn Foundation for Medical Research, Korea University grant nos. K2006261 and K2025261; the National Research Foundation of Korea Government grant nos. NRF 2020R1C1C1009921 (O.H.J.) and NIH T32 AG002266 (N.W.A.); the Pew Charitable Trust awarded to the Buck Institute for Research on Aging; by grants from the NIH nos. P01 AG017242 and R01 AG051729 (J.C.); grant nos. NIH 1R01AG071787, R56 AG058819, R01 EB023776, R01 HL139605, and the Open Philanthropy Foundation and the QB3 Calico Award (I.M.C.). A collaborative grant no. R56 AG052988 SA23061 (J.C. and I.M.C.) greatly aided these studies. Schematics of all experimental designs were created with BioRender.com.
Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2022/8
Y1 - 2022/8
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85137124273&partnerID=8YFLogxK
U2 - 10.1038/s42255-022-00609-6
DO - 10.1038/s42255-022-00609-6
M3 - Article
C2 - 35902645
AN - SCOPUS:85137124273
SN - 2522-5812
VL - 4
SP - 995
EP - 1006
JO - Nature Metabolism
JF - Nature Metabolism
IS - 8
ER -
