Inconclusive Effects on Telomere Length from the CALERIE 2 Study
In recent years, researchers have been putting more effect into analyses of the CALERIE 2 study of human calorie restriction. The study took place some years ago, but new results continue to be published. Here, researchers show that effects on telomere length and a related aging clock are inconclusive. Telomere length measured in the white blood cells of a blood sample is not a great measure of aging. It is highly variable between individuals, is influenced day to day changes in immune status, and it takes a fairly large study group for age-related trends to show up. It has rightfully been eclipsed by the development of aging clocks derived from omics data.
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 21-50 years; BMI 22.0-27.9 kg/m2), 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, DNA methylation estimated telomere length (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.