There is currently a theory called the geroscience hypothesis that suggests that slowing or reversing the molecular changes that coincide with aging can delay the onset of multiple chronic diseases and slow aging. Caloric restriction is an example of an intervention that causes molecular changes and is defined as reducing the intake of calories without restricting essential nutrients. This paper looked at how calorie restriction may support the geroscience hypothesis and how calorie restriction influences aging. Data was analysed from a randomized controlled trial named the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE) trial, which assigned 220 adults without obesity to a 25% calorie reduction. After two years, the authors found that reducing calories by 25% slowed the pace of aging. These findings support the geroscience hypothesis and that introducing molecular changes may not only slow aging but help prevent and control chronic disease.
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 lifespan1,2,3. 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)5,6,7, 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 health11,12,13. The finding that CR modified DunedinPACE in a randomized controlled trial supports the geroscience hypothesis, building on evidence from small and uncontrolled studies14,15,16 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 mortality18,19,20.
Article Publication Date: 20/04/2022