Senolytics improve physical function and increase lifespan in old age.

Abstract:

:Physical function declines in old age, portending disability, increased health expenditures, and mortality. Cellular senescence, leading to tissue dysfunction, may contribute to these consequences of aging, but whether senescence can directly drive age-related pathology and be therapeutically targeted is still unclear. Here we demonstrate that transplanting relatively small numbers of senescent cells into young mice is sufficient to cause persistent physical dysfunction, as well as to spread cellular senescence to host tissues. Transplanting even fewer senescent cells had the same effect in older recipients and was accompanied by reduced survival, indicating the potency of senescent cells in shortening health- and lifespan. The senolytic cocktail, dasatinib plus quercetin, which causes selective elimination of senescent cells, decreased the number of naturally occurring senescent cells and their secretion of frailty-related proinflammatory cytokines in explants of human adipose tissue. Moreover, intermittent oral administration of senolytics to both senescent cell-transplanted young mice and naturally aged mice alleviated physical dysfunction and increased post-treatment survival by 36% while reducing mortality hazard to 65%. Our study provides proof-of-concept evidence that senescent cells can cause physical dysfunction and decreased survival even in young mice, while senolytics can enhance remaining health- and lifespan in old mice.

journal_name

Nat Med

journal_title

Nature medicine

authors

Xu M,Pirtskhalava T,Farr JN,Weigand BM,Palmer AK,Weivoda MM,Inman CL,Ogrodnik MB,Hachfeld CM,Fraser DG,Onken JL,Johnson KO,Verzosa GC,Langhi LGP,Weigl M,Giorgadze N,LeBrasseur NK,Miller JD,Jurk D,Singh RJ,Allison

doi

10.1038/s41591-018-0092-9

subject

Has Abstract

pub_date

2018-08-01 00:00:00

pages

1246-1256

issue

8

eissn

1078-8956

issn

1546-170X

pii

10.1038/s41591-018-0092-9

journal_volume

24

pub_type

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