Research

Hormonal

Long-term moderate caloric restriction (~30% reduction) in healthy, weight-stable adults inhibits the PI3K/AKT signaling pathway and induces a transcriptional profile in skeletal muscle that resembles that of younger individuals.

For middle-aged adults, maintaining a moderate caloric deficit (approx. 30% below maintenance) while ensuring full nutritional adequacy and weight stability for several years may trigger molecular changes in muscle that mimic youth, specifically by dampening growth-signaling pathways (PI3K/AKT) and boosting repair mechanisms. This suggests that long-term, disciplined eating habits may offer biological benefits beyond simple weight management.

GoodSupportsHIGH confidence
Here we report that long-term CR in humans inhibits the IGF-1/insulin pathway in skeletal muscle... We also demonstrate that CR-induced dramatic changes of the skeletal muscle transcriptional profile that resemble those of younger individuals.
Evi M. Mercken et al. · Aging Cell · 2013

Why this rating

Observational study of a specific, self-selected population (Calorie Restriction Society members) with long-term adherence, compared to controls; lacks randomization but has rigorous molecular analysis.

Source

Calorie restriction in humans inhibits the <scp>PI</scp>3<scp>K</scp>/<scp>AKT</scp> pathway and induces a younger transcription profile

Evi M. Mercken et al. · Aging Cell · 2013

DOI 10.1111/acel.12088

cross_sectional · n=25Cited 244×
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DOI resolved against Crossref · corpus check 2026-06-10

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