CALERIE™ Legacy Study: Design of the Longitudinal Follow-Up Study of Participants in the CALERIE™ 2 Trial

Le résumé fourni par la source

Calorie restriction (CR), defined as a reduction in calorie intake without compromising nutrient status, directly targets the biology of aging, thereby delaying the onset and slowing the progression of age-related diseases. CR is a geroprotective strategy to extend healthspan, which is the number of years lived in good health, without chronic diseases, significant impairments, or a poor quality of life. The Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE) 2 trial was the first randomized controlled trial to investigate the effects of long-term CR on biomarkers of aging and healthspan in healthy adults without obesity. Results of the multi-site CALERIE 2 trial revealed that healthy young and middle-aged adults randomized to a 2-year CR intervention experienced slower biological aging and improved markers of healthspan both within group and relative to an ad libitum control group. The CR group achieved an average 11.9±0.7% CR (mean±SE) during the 2-year CR intervention. The gap in knowledge that remains is whether CR results in long-term benefits after cessation of a structured intervention. The CALERIE Legacy Study was designed to address this gap by testing the hypothesis that a CR intervention in early to mid-adulthood results in sustained lower rates of biological aging, delayed manifestations of phenotypic aging, and superior indices of functional aging compared to ad libitum intake. CALERIE Legacy is an observational follow-up study of CALERIE 2 trial participants 12 to 15 years after their trial engagement. CALERIE 2 participants in the CR intervention group are being compared to a control group comprised of CALERIE 2 control group participants and a matched subset of participants in the Baltimore Longitudinal Study of Aging. The primary outcomes of the CALERIE Legacy Study are biological aging, evaluated with the Klemera-Doubal method, and healthspan, based on the metabolic syndrome score. Secondary outcomes include other indices of biological aging (i.e., Homeostatic Dysregulation Index and Levine phenotypic age), biomarkers proposed by the Targeting Aging with MEtformin (TAME) Biomarkers Workgroup, and several other blood and urine-based biomarkers (i.e., senescence-associated secretory phenotype proteins, growth differentiation factor 15, N-terminal pro-B-type natriuretic peptide, cystatin C, tumor necrosis factor receptor II, and urinary isoprostanes). The comprehensive assessment battery includes body composition by dual-energy x-ray absorptiometry, resting metabolic rate by indirect calorimetry, cardiorespiratory fitness with a maximal oxygen uptake treadmill test, knee extensor and flexor muscle power by isokinetic and isometric dynamometry, hand grip strength, short physical performance battery, Cambridge Neuropsychological Test Automated Battery (CANTAB), and a series of standardized questionnaires addressing quality of life, resilience, depression, sleep, dietary intake, and physical activity. The CALERIE Legacy Study was designed to advance our understanding of the long-term impact of CR in early-to-mid adult life on human aging. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

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