@article{d82c98ce173b433f9b53b7245f843fa3,
title = "Effect of long-term caloric restriction on DNA methylation measures of biological aging in healthy adults from the CALERIE trial",
abstract = "The geroscience hypothesis proposes that therapy to slow or reverse molecular changes that occur with aging can delay or prevent multiple chronic diseases and extend healthy lifespan1–3. Caloric restriction (CR), defined as lessening caloric intake without depriving essential nutrients4, results in changes in molecular processes that have been associated with aging, including DNA methylation (DNAm)5–7, and is established to increase healthy lifespan in multiple species8,9. Here we report the results of a post hoc analysis of the influence of CR on DNAm measures of aging in blood samples from the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE) trial, a randomized controlled trial in which n = 220 adults without obesity were randomized to 25% CR or ad libitum control diet for 2 yr (ref. 10). We found that CALERIE intervention slowed the pace of aging, as measured by the DunedinPACE DNAm algorithm, but did not lead to significant changes in biological age estimates measured by various DNAm clocks including PhenoAge and GrimAge. Treatment effect sizes were small. Nevertheless, modest slowing of the pace of aging can have profound effects on population health11–13. The finding that CR modified DunedinPACE in a randomized controlled trial supports the geroscience hypothesis, building on evidence from small and uncontrolled studies14–16 and contrasting with reports that biological aging may not be modifiable17. Ultimately, a conclusive test of the geroscience hypothesis will require trials with long-term follow-up to establish effects of intervention on primary healthy-aging endpoints, including incidence of chronic disease and mortality18–20.",
author = "R. Waziry and Ryan, {C. P.} and Corcoran, {D. L.} and Huffman, {K. M.} and Kobor, {M. S.} and M. Kothari and Graf, {G. H.} and Kraus, {V. B.} and Kraus, {W. E.} and Lin, {D. T.S.} and Pieper, {C. F.} and Ramaker, {M. E.} and M. Bhapkar and Das, {S. K.} and L. Ferrucci and Hastings, {W. J.} and M. Kebbe and Parker, {D. C.} and Racette, {S. B.} and I. Shalev and B. Schilling and Belsky, {D. W.}",
note = "Funding Information: {\textquoteleft}CALERIE{\textquoteright} is a registered trademark. This research was supported by grant no. R01AG061378 (to D.W.B.). R.W. received additional support from the American Brain Foundation (to R.W.). C.F.P. and V.B.K. received additional support from grant no. P30AG028716 (to C.F.P. and V.B.K.); V.B.K. received additional support from grant no. R01AG054840 (to V.B.K.); K.M.H., W.E.K. and C.F.P. received additional support from grant no. R33AG070455 (to K.M.H., W.E.K. and C.F.P.); M.S.K. received additional support from the CIHR grant no. RN439810 (to M.S.K.); S.B.R., M.B. and S.K.D. received support from grant no. R01 AG071717 (to S.B.R., M.B. and S.K.D.); I.S. and W.J.H. received support from grant no. R03AG071549 (to I.S.). B.S. received support from grant no. U01AG060906 (to B.S.). We thank the CALERIE Research Network no. R33AG070455 for their assistance in this project and the Dunedin Study no. R01AG032282 for facilitating early access to the DunedinPACE DNA methylation algorithm. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the paper. R.W. completed work on this project while affiliated with the Butler Columbia Aging Center. She is now in the Department of Neurology at the Columbia University Irving Medical Center. Publisher Copyright: {\textcopyright} 2023, The Author(s).",
year = "2023",
doi = "10.1038/s43587-022-00357-y",
language = "English (US)",
journal = "Nature Aging",
issn = "2662-8465",
publisher = "Springer",
}
