Caloric restriction modifies small RNA profiles and engages age-related molecular pathways in the CALERIE trial.

ABSTRACT: Caloric restriction (CR) extends lifespan and enhances healthspan across species. In humans, the CALERIE Phase 2 trial demonstrated that CR improves inflammation, cardiometabolic health, and molecular aging. To explore underlying mechanisms, we examined CR-induced changes vs. ad libitum (AL) in small non-coding RNAs (smRNAs) across plasma, muscle, and adipose tissue. Using smRNA sequencing, we analyzed microRNAs (miRs) and piwi-interacting RNAs (piRs) over 12 and 24 months, comparing CR levels (%CR) and group assignments (CR vs. AL). We identified 16 smRNAs associated with %CR and 41 with CR vs. AL. Although tissue-specific expression varied, shared pathways emerged, including insulin signaling, circadian rhythm, cell cycle regulation, and stress response. Cross-species analysis rev

SUBMITTER: Orenduff MC 

PROVIDER: S-EPMC12811477 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature