PMID- 37118425
OWN - NLM
STAT- MEDLINE
DCOM- 20230501
LR  - 20240423
IS  - 2662-8465 (Electronic)
IS  - 2662-8465 (Linking)
VI  - 3
IP  - 3
DP  - 2023 Mar
TI  - Effect of long-term caloric restriction on DNA methylation measures of biological 
      aging in healthy adults from the CALERIE trial.
PG  - 248-257
LID - 10.1038/s43587-022-00357-y [doi]
AB  - 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 lifespan(1-3). Caloric restriction (CR), defined as lessening 
      caloric intake without depriving essential nutrients(4), 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 species(8,9). 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 health(11-13). The finding that CR 
      modified DunedinPACE in a randomized controlled trial supports the geroscience 
      hypothesis, building on evidence from small and uncontrolled studies(14-16) and 
      contrasting with reports that biological aging may not be modifiable(17). 
      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 
      mortality(18-20).
CI  - (c) 2023. The Author(s).
FAU - Waziry, R
AU  - Waziry R
AD  - Butler Columbia Aging Center, Columbia University Mailman School of Public 
      Health, New York, NY, USA.
FAU - Ryan, C P
AU  - Ryan CP
AD  - Butler Columbia Aging Center, Columbia University Mailman School of Public 
      Health, New York, NY, USA.
FAU - Corcoran, D L
AU  - Corcoran DL
AD  - Department of Genetics, University of North Carolina at Chapel Hill School of 
      Medicine, Chapel Hill, NC, USA.
FAU - Huffman, K M
AU  - Huffman KM
AD  - Duke Molecular Physiology Institute and Department of Medicine, Duke University 
      School of Medicine, Durham, NC, USA.
FAU - Kobor, M S
AU  - Kobor MS
AD  - Department of Medical Genetics, Edwin S.H. Leong Healthy Aging Program, Centre 
      for Molecular Medicine and Therapeutics, University of British Columbia, 
      Vancouver, British Columbia, Canada.
FAU - Kothari, M
AU  - Kothari M
AD  - Butler Columbia Aging Center, Columbia University Mailman School of Public 
      Health, New York, NY, USA.
FAU - Graf, G H
AU  - Graf GH
AD  - Butler Columbia Aging Center, Columbia University Mailman School of Public 
      Health, New York, NY, USA.
AD  - Department of Epidemiology, Columbia University Mailman School of Public Health, 
      New York, NY, USA.
FAU - Kraus, V B
AU  - Kraus VB
AUID- ORCID: 0000-0001-8173-8258
AD  - Duke Molecular Physiology Institute and Department of Medicine, Duke University 
      School of Medicine, Durham, NC, USA.
FAU - Kraus, W E
AU  - Kraus WE
AUID- ORCID: 0000-0003-1930-9684
AD  - Duke Molecular Physiology Institute and Department of Medicine, Duke University 
      School of Medicine, Durham, NC, USA.
FAU - Lin, D T S
AU  - Lin DTS
AD  - Department of Medical Genetics, Edwin S.H. Leong Healthy Aging Program, Centre 
      for Molecular Medicine and Therapeutics, University of British Columbia, 
      Vancouver, British Columbia, Canada.
FAU - Pieper, C F
AU  - Pieper CF
AD  - Center on Aging and Development, Biostatistics and Bioinformatics, Duke 
      University, Durham, NC, USA.
FAU - Ramaker, M E
AU  - Ramaker ME
AD  - Duke Molecular Physiology Institute and Department of Medicine, Duke University 
      School of Medicine, Durham, NC, USA.
FAU - Bhapkar, M
AU  - Bhapkar M
AD  - Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC, 
      USA.
FAU - Das, S K
AU  - Das SK
AD  - Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, 
      Boston, MA, USA.
FAU - Ferrucci, L
AU  - Ferrucci L
AUID- ORCID: 0000-0002-6273-1613
AD  - Translational Gerontology Branch, National Institute on Aging, National 
      Institutes of Health, Baltimore, MD, USA.
FAU - Hastings, W J
AU  - Hastings WJ
AD  - Department of Biobehavioral Health, Pennsylvania State University, State College, 
      PA, USA.
FAU - Kebbe, M
AU  - Kebbe M
AD  - Pennington Biomedical Research Center, Baton Rouge, LA, USA.
FAU - Parker, D C
AU  - Parker DC
AUID- ORCID: 0000-0001-8512-1044
AD  - Department of Medicine, Duke University School of Medicine, Durham, NC, USA.
FAU - Racette, S B
AU  - Racette SB
AUID- ORCID: 0000-0002-6932-1887
AD  - Program in Physical Therapy and Department of Medicine, Washington University 
      School of Medicine, St. Louis, MO, USA.
AD  - College of Health Solutions, Arizona State University, Phoenix, AZ, USA.
FAU - Shalev, I
AU  - Shalev I
AD  - Department of Biobehavioral Health, Pennsylvania State University, State College, 
      PA, USA.
FAU - Schilling, B
AU  - Schilling B
AUID- ORCID: 0000-0001-9907-2749
AD  - Buck Institute for Research on Aging, Novato, CA, USA.
FAU - Belsky, D W
AU  - Belsky DW
AUID- ORCID: 0000-0001-5463-2212
AD  - Butler Columbia Aging Center, Columbia University Mailman School of Public 
      Health, New York, NY, USA. Daniel.Belsky@Columbia.edu.
AD  - Department of Epidemiology, Columbia University Mailman School of Public Health, 
      New York, NY, USA. Daniel.Belsky@Columbia.edu.
LA  - eng
GR  - R01 AG061378/AG/NIA NIH HHS/United States
GR  - U24 AG066528/AG/NIA NIH HHS/United States
GR  - R01 AG066887/AG/NIA NIH HHS/United States
GR  - R03 AG071549/AG/NIA NIH HHS/United States
GR  - P30 AG028716/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20230209
PL  - United States
TA  - Nat Aging
JT  - Nature aging
JID - 101773306
SB  - IM
EIN - Nat Aging. 2023 Jun;3(6):753. PMID: 37161091
MH  - Humans
MH  - Adult
MH  - *Caloric Restriction/methods
MH  - *DNA Methylation
MH  - Energy Intake
MH  - Aging/genetics
MH  - Longevity
PMC - PMC10148951
MID - NIHMS1860504
COIS- D.L.C. and D.W.B. are listed as inventors on a Duke University and University of 
      Otago invention, DunedinPACE, that was licensed to a commercial entity. The other 
      authors declare no competing interests.
EDAT- 2023/04/29 06:04
MHDA- 2023/05/01 06:42
PMCR- 2023/02/09
CRDT- 2023/04/28 23:41
PHST- 2021/09/08 00:00 [received]
PHST- 2022/12/22 00:00 [accepted]
PHST- 2023/05/01 06:42 [medline]
PHST- 2023/04/29 06:04 [pubmed]
PHST- 2023/04/28 23:41 [entrez]
PHST- 2023/02/09 00:00 [pmc-release]
AID - 10.1038/s43587-022-00357-y [pii]
AID - 357 [pii]
AID - 10.1038/s43587-022-00357-y [doi]
PST - ppublish
SO  - Nat Aging. 2023 Mar;3(3):248-257. doi: 10.1038/s43587-022-00357-y. Epub 2023 Feb 
      9.