The effects of caloric restriction on adipose tissue and metabolic health are sex-and age-dependent.

Funding Information: This work was supported by grants from the Medical Research Council (MR/M021394/1 to W.P.C.), the British Heart Foundation (BHF) (RG/16/10/32375 and FS/19/34/34354 to A.A.S.T.; 4-year BHF PhD Studentship to B.J.T. and R.J.S.), the Takeda Science Foundation (Fellowship for Young Japanese MDs & PhDs Studying Abroad, to Y.M.I.), the Japan Society for the Promotion of Science (JSPS Overseas Research Fellowship, to Y.M.I.), the Japan Foundation for Applied Enzymology (to Y.M.I.), the University of Edinburgh (Chancellor’s Fellowship to W.P.C.; PhD Studentship to A.L.), the Carnegie Trust (RIG007416 to W.P.C.), the Wellcome Trust (Technology Development Award 221295/Z/20/Z to A.A.S.T.; Multi-user equipment grant 223818/Z/21/Z for the Promethion system), the Chief Scientist Office of the Scottish Government (SCAF/17/02 to R.H.S.), KAKENHI grants from MEXT/JSPS (21K08431 to H.K.), and a grant from the National Center for Global Health and Medicine (20A1010 to H.K.). C.F. and A.M.J. gratefully acknowledge financial support from the Scottish Government as part of the RESAS Strategic Research Programme at the Rowett Institute, University of Aberdeen. We thank Ami Onishi for assistance with indirect calorimetry studies using the Promethion system, and the BHF for supporting Ami Onishi’s salary through the Centre for Research Excellence Award III (RE/18/5/34216). The BHF also provided funding towards establishment of the Edinburgh Preclinical PET/CT laboratory (RE/13/3/30183) and support of the 2018 Very Important Project (VIP) PET prize, for which we are grateful. Finally, we thank Dr Matthew Bennett (University of Edinburgh) for advice analysing RNA-seq data; Prof Robert Semple (University of Edinburgh) and Prof Ormond MacDougald (University of Michigan) for helpful advice to interpret our findings; Stefanie Fung (University of Edinburgh) for assistance isolating RNA for RNA-seq; Dr Hai-Bin Ruan (University of Minnesota Medical School) and Dr Eleonora Pagano (Pontifical Catholic University of Argentina) for kindly providing a full text of Ballor and Poehlman’s 1994 study (78), and all staff at Edinburgh Bioresearch & Veterinary Services for their superb technical support. Finally, this manuscript was written entirely by the authors and without any use of large language models. Publisher Copyright: © 2023, eLife Sciences Publications Ltd. All rights reserved.Peer reviewedPublisher PD