Fig. 8: Is rapamycin a calorie restriction mimetic?
From: Distinct and additive effects of calorie restriction and rapamycin in aging skeletal muscle
A Calorie restriction (CR) induces broad changes in activity (e.g., anticipatory behavior), metabolism (e.g., reduced metabolic rate), nutrition (e.g., nutrient stress and temporally compressed food intake) and body composition (e.g., reduced body mass and lean phenotype). B Long-term CR promotes a slow, pro-endurance muscle phenotype including improved endurance performance, slower contraction speeds and a fast-to-slow fiber type shift, particularly in the depicted soleus muscle. C CR suppresses mTORC1 activity by lowering the availability of its positive regulators, including growth factors, energy, and amino acids, leading to reduced translation and increased autophagy. D Despite both RM and CR suppressing mTORC1 activity, long-term treatments exert distinct and often opposing molecular signatures in aging skeletal muscle. E CR improves muscle quality in TSCmKO mice, which display sustained, nutrient-insensitive mTORC1 activity and a premature sarcopenic phenotype, indicating that muscle mTORC1 suppression is not required for CR-induced benefits. F While CR and RM both improve whole-body muscle function and promote a fast-to-slow fiber type switch, the effects are frequently additive in calorie-restricted mice treated with RM. Together, these data demonstrate that RM is not a CR mimetic, but could rather be an adjunct therapy for CR-like interventions. Figure created with BioRender.com.
