Yang · Cell reports 2016 · cross-sectional comparative study · n=?

Long-Term Calorie Restriction Enhances Cellular Quality-Control Processes in Human Skeletal Muscle.

Cited 166 times in the scientific literature.

Level 4 - case-series / case-control

Cross-sectional comparative study with non-randomized, self-selected human cohorts.

PubMed 26774472 · doi:10.1016/j.celrep.2015.12.042 · record verified 2026-08-30

What was done

Researchers measured serum cortisol and molecular chaperones and autophagic proteins in skeletal muscle biopsies from individuals practicing long-term calorie restriction (CR) for 3–15 years, comparing them against age-matched sedentary controls and endurance athlete controls.

What was found

Serum cortisol was significantly higher in the CR group compared to sedentary and endurance athlete groups (15.6 ± 4.6 ng/dl versus 12.3 ± 3.9 ng/dl and 11.2 ± 2.7 ng/dl, respectively; p ≤ 0.001). Skeletal muscle HSP70, Grp78, beclin-1, and LC3 mRNA and/or protein levels were higher in the CR group compared to controls (no numerical values or effect sizes reported in the abstract for muscle markers).

Why it matters

This study provides evidence that multi-year calorie restriction in humans is associated with sustained elevations in serum cortisol and upregulation of protein quality-control and autophagy markers in skeletal muscle.

Limits

Cross-sectional observational design prevents establishing causality. The abstract does not report the sample size (n), participant demographics, or exact numerical/statistical values for the muscle chaperones and autophagy proteins. Static markers do not directly measure dynamic autophagic flux.

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