M. Dirmontas, P. Minderis and A. Ratkevicius (2026). Effects of Aging in Combination with High-Fat or Ketogenic Diet on Skeletal Muscle Atrophy Following Denervation in C57BL/6J Mice. Nutrients, 18(3). https://doi.org/10.3390/nu18030478

PubMed 41683300

[Abstract]
OBJECTIVES: The aim of this study was to investigate the effect of the interaction between aging and high-fat diet (HFD) or ketogenic diet (KD) on denervation-induced muscle atrophy.

METHODS: In this study, 6-, 19- and 27-month-old male mice were studied after 12 weeks' exposure to a regular chow diet, RD (kcal distribution: 13% fat, 57% carbohydrate, 30% protein), HFD (kcal distribution: 60% fat, 20% carbohydrates, 20% protein), or KD (kcal distribution: 80% fat, <1% carbohydrates, 20% protein). Gastrocnemius (GAS) and soleus (SOL) muscles were left denervated during the last 6 weeks of this 12-week dietary intervention (n = 10 for each group).

RESULTS: Denervation-induced atrophy was greater (p < 0.001) in GAS compared to SOL. There were no differences between type 1 and type 2 muscle fiber atrophy in adult SOL muscle. Muscle atrophy did not depend on the diet and was greater in adult than old mice. Both HFD and KD feeding reduced IGF-1 levels (p < 0.01) in GAS muscle compared with the RD independently of age. Myostatin levels in GAS muscle increased (p < 0.01) with age independently of the diets.

CONCLUSIONS: Denervation-induced muscle atrophy does not depend on dietary fat intake and proceeds at a slower rate in old mice compared to adult mice.