Calorie restriction modulates the transcription of genes related to stress response and longevity in human muscle: The CALERIE study.
Level 2 - randomized trial
Randomized controlled trial sub-study
PubMed 37823711 · doi:10.1111/acel.13963
What was done
High-depth RNA-sequencing (387-618 million paired reads) was conducted on vastus lateralis muscle biopsies from 90 healthy participants enrolled in the CALERIE randomized controlled trial. Biopsies taken at baseline, 12 months, and 24 months were compared between participants randomized to caloric restriction (achieved ~12% CR) versus ad libitum controls using linear mixed-effects models.
What was found
The abstract reports no numerical effect sizes, fold changes, or p-values. It reports that 2 years of 12% caloric restriction resulted in minor losses of leg lean mass without changes in muscle strength. Caloric restriction significantly altered the transcription and alternative splicing of genes related to proteostasis, circadian rhythm regulation, DNA repair, mitochondrial biogenesis, mRNA processing/splicing, FOXO3 metabolism, apoptosis, and inflammation compared to controls, mediating preserved muscle quality.
Why it matters
This study provides randomized human evidence that achievable caloric restriction modulates conserved longevity and stress-response pathways in skeletal muscle, mirroring biological mechanisms previously established in animal models.
Limits
The abstract provides no exact quantitative values, fold changes, or statistical confidence intervals. Findings are limited to a healthy human cohort and vastus lateralis muscle tissue, so generalizability to older or sarcopenic populations is uncertain, and downstream functional protein translation was not reported.
Cited by
- partial Eating 15% fewer calories has been shown in multiple randomized trials to have a major impact on boosting mitochondrial health.