Effects of aging in combination with high-fat or ketogenic diet on skeletal muscle hypertrophy after functional overloading in C57BL/6J mice

We investigated how aging interacts with high-fat (HFD) and ketogenic (KD) diets to influence functional overload (FO)-induced muscle hypertrophy in C57BL/6J mice. Male mice aged 3, 16, and 24 months were fed regular chow (RD), HFD, or KD for 12 weeks, with FO of the plantaris muscle induced by denervation of the soleus and gastrocnemius during the final 6 weeks (n = 8-10 per group). Muscle hypertrophy was unaffected by diet (p = 0.897) but declined with age (p < 0.001), with a marked reduction already in mature mice. Plasma IGF-1 was higher in adult than mature (p < 0.05) and old (p < 0.001) mice and correlated positively with hypertrophy (r = 0.29, p = 0.01). The weak correlation of hypertrophy with plasma IGF-I levels suggests that IGF-I is only one among many factors playing a role in muscle hypertrophy.