{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Hastings WJ"],"funding":["NIA NIH HHS","NIDDK NIH HHS","NIEHS NIH HHS","NIGMS NIH HHS"],"pagination":["e14149"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11296136"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["23(6)"],"pubmed_abstract":["Caloric restriction (CR) modifies lifespan and aging biology in animal models. The Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy (CALERIE™) 2 trial tested translation of these findings to humans. CALERIE™ randomized healthy, nonobese men and premenopausal women (age 21-50y; BMI 22.0-27.9 kg/m<sup>2</sup>), to 25% CR or ad-libitum (AL) control (2:1) for 2 years. Prior analyses of CALERIE™ participants' blood chemistries, immunology, and epigenetic data suggest the 2-year CR intervention slowed biological aging. Here, we extend these analyses to test effects of CR on telomere length (TL) attrition. TL was quantified in blood samples collected at baseline, 12-, and 24-months by quantitative PCR (absolute TL; aTL) and a published DNA-methylation algorithm (DNAmTL). Intent-to-treat analysis found no significant differences in TL attrition across the first year, although there were trends toward increased attrition in the CR group for both aTL and DNAmTL measurements. When accounting for adherence heterogeneity with an Effect-of-Treatment-on-the-Treated analysis, greater CR dose was associated with increased DNAmTL attrition during the baseline to 12-month weight-loss period. By contrast, both CR group status and increased CR were associated with reduced aTL attrition over the month 12 to month 24 weight maintenance period. No differences were observed when considering TL change across the study duration from baseline to 24-months, leaving it unclear whether CR-related effects reflect long-term detriments to telomere fidelity, a hormesis-like adaptation to decreased energy availability, or measurement error and insufficient statistical power. Unraveling these trends will be a focus of future CALERIE™ analyses and trials."],"journal":["Aging cell"],"pubmed_title":["Effect of long-term caloric restriction on telomere length in healthy adults: CALERIE™ 2 trial analysis."],"pmcid":["PMC11296136"],"funding_grant_id":["R03 AG071549","U24 AG047121","U54 GM104940","R33 AG070455","U01 AG020480","U01 AG022132","P30 DK072476","U01 AG073204","R01 AG071717","U01 AG020487","T32 AG049676","U01 ES030949","U01 AG020478","R01 AG061378","U24 AG066528"],"pubmed_authors":["Redman LM","Hastings WJ","Wolf SE","Shalev I","Belsky DW","Kobor MS","Ye Q","Das SK","Martin CK","MacIsaac JL","Racette SB","Ryan CP","Kraus WE","Huffman KM"],"additional_accession":[]},"is_claimable":false,"name":"Effect of long-term caloric restriction on telomere length in healthy adults: CALERIE™ 2 trial analysis.","description":"Caloric restriction (CR) modifies lifespan and aging biology in animal models. The Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy (CALERIE™) 2 trial tested translation of these findings to humans. CALERIE™ randomized healthy, nonobese men and premenopausal women (age 21-50y; BMI 22.0-27.9 kg/m<sup>2</sup>), to 25% CR or ad-libitum (AL) control (2:1) for 2 years. Prior analyses of CALERIE™ participants' blood chemistries, immunology, and epigenetic data suggest the 2-year CR intervention slowed biological aging. Here, we extend these analyses to test effects of CR on telomere length (TL) attrition. TL was quantified in blood samples collected at baseline, 12-, and 24-months by quantitative PCR (absolute TL; aTL) and a published DNA-methylation algorithm (DNAmTL). Intent-to-treat analysis found no significant differences in TL attrition across the first year, although there were trends toward increased attrition in the CR group for both aTL and DNAmTL measurements. When accounting for adherence heterogeneity with an Effect-of-Treatment-on-the-Treated analysis, greater CR dose was associated with increased DNAmTL attrition during the baseline to 12-month weight-loss period. By contrast, both CR group status and increased CR were associated with reduced aTL attrition over the month 12 to month 24 weight maintenance period. No differences were observed when considering TL change across the study duration from baseline to 24-months, leaving it unclear whether CR-related effects reflect long-term detriments to telomere fidelity, a hormesis-like adaptation to decreased energy availability, or measurement error and insufficient statistical power. Unraveling these trends will be a focus of future CALERIE™ analyses and trials.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Jun","modification":"2025-04-19T20:49:33.419Z","creation":"2025-02-19T02:27:33.576Z"},"accession":"S-EPMC11296136","cross_references":{"pubmed":["38504468"],"doi":["10.1111/acel.14149"]}}