TY - JOUR
T1 - Circadian alignment of early onset caloric restriction promotes longevity in male C57BL/6J mice
AU - Acosta-Rodríguez, Victoria
AU - Rijo-Ferreira, Filipa
AU - Izumo, Mariko
AU - Xu, Pin
AU - Wight-Carter, Mary
AU - Green, Carla B
AU - Takahashi, Joseph S
N1 - Funding Information:
We thank G. Martinez, C. Joseph, K. Brown, and D. Bassowou for assistance with animal care and maintenance; I. Kornblum for preparing mRNA-seq libraries; G. Kilaru for mapping NGS files; and S. Yamazaki for helpful discussions. We apologize for the omission of relevant citations because of space constraints. This work was supported by the Howard Hughes Medical Institute (J.S.T.); the National Institutes of Health (NIH) National Institute on Aging (grant R01 AG045795 and R56 AG072736 to J.S.T. and C.B.G.); the NIH National Institute of General Medical Sciences (NIGMS) (grant R35 GM127122 to C.B.G. and grant K99 GM132557 to F.R.-F.); and the Milky Way Research Foundation (grant MWRF210823 to J.S.T. and C.B.G.). J.S.T. is an investigator and F.R.-F. was an associate at the Howard Hughes Medical Institute.
Publisher Copyright:
Copyright © 2022 The Authors, some rights reserved
PY - 2022/6/10
Y1 - 2022/6/10
N2 - Caloric restriction (CR) prolongs life span, yet the mechanisms by which it does so remain poorly understood. Under CR, mice self-impose chronic cycles of 2-hour feeding and 22-hour fasting, raising the question of if it is calories, fasting, or time of day that is the cause of this increased life span. We show here that 30% CR was sufficient to extend the life span by 10%; however, a daily fasting interval and circadian alignment of feeding acted together to extend life span by 35% in male C57BL/6J mice. These effects were independent of body weight. Aging induced widespread increases in gene expression associated with inflammation and decreases in the expression of genes encoding components of metabolic pathways in liver from ad libitum–fed mice. CR at night ameliorated these aging-related changes. Our results show that circadian interventions promote longevity and provide a perspective to further explore mechanisms of aging.
AB - Caloric restriction (CR) prolongs life span, yet the mechanisms by which it does so remain poorly understood. Under CR, mice self-impose chronic cycles of 2-hour feeding and 22-hour fasting, raising the question of if it is calories, fasting, or time of day that is the cause of this increased life span. We show here that 30% CR was sufficient to extend the life span by 10%; however, a daily fasting interval and circadian alignment of feeding acted together to extend life span by 35% in male C57BL/6J mice. These effects were independent of body weight. Aging induced widespread increases in gene expression associated with inflammation and decreases in the expression of genes encoding components of metabolic pathways in liver from ad libitum–fed mice. CR at night ameliorated these aging-related changes. Our results show that circadian interventions promote longevity and provide a perspective to further explore mechanisms of aging.
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U2 - 10.1126/science.abk0297
DO - 10.1126/science.abk0297
M3 - Article
C2 - 35511946
AN - SCOPUS:85130998257
SN - 0036-8075
VL - 376
SP - 1192
EP - 1202
JO - Science
JF - Science
IS - 6598
ER -