Prolonged caloric restriction ameliorates age-related atrophy in slow and fast muscle fibers of rat soleus muscle

Aging causes loss of skeletal muscle mass and function, which is called sarcopenia. While sarcopenia impairs the quality of life of older adults and is a major factor in long-term hospitalization, its detailed pathogenic mechanism and preventive measures remain to be identified. Caloric restriction (CR) suppresses age-related physiological and pathological changes in many species and prolongs the average and healthy life expectancy. It has recently been reported that CR suppresses the onset of sarcopenia; however, few studies have analyzed the effects of long-term CR on age-related skeletal muscle atrophy. Thus, we investigated the aging and CR effects on soleus (SOL) muscles of 9-, 24-, and 29-month-old ad libitum-fed rats (9AL, 24AL, and 29AL, respectively) and of 29-month-old CR (29CR) rats. The total muscle cross sectional area (mCSA) of the entire SOL muscle significantly decreased in the 29AL rats, but not in the 24AL rats, compared with the 9AL rats. SOL muscle of the 29AL rats exhibited marked muscle fiber atrophy and increases in the number of muscle fibers with a central nucleus, in fibrosis, and in adipocyte infiltration. Additionally, although the decrease in the single muscle fiber cross-sectional area (fCSA) and the muscle fibers' number occurred in both slow-type and fast-type muscle fibers, the degree of atrophy was more remarkable in the fast-type fibers. However, CR suppressed the muscle fiber atrophy observed in the 29AL rats' SOL muscle by preserving the mCSA and the number of muscle fibers that declined with aging, and by decreasing the number of muscle fibers with a central nucleus, fibrosis and denervated muscle fibers. Overall, these results revealed that advanced aging separately reduces the number and fCSA of each muscle fiber type, but long-term CR can ameliorate this age-related sarcopenic muscle atrophy.