The role of dietary restriction in age-related muscle atrophy. Guiping Du, Jennika Krisa, Patrick Li, Subhash Katewa, Aric Rogers, Matthew Laye, Pankaj Kapahi. Buck Institute for Research on Aging, Novato, CA.

   Age-related loss of muscle mass (sarcopenia), is one of the major problems compromising the health condition of the aged population. Therefore, uncovering the molecular mechanisms of age-related muscle atrophy and understanding the correlation between muscle activity and aging progression are of great importance. Dietary restriction (DR), which extends lifespan and slows down the progression of various age-associated diseases, enhances spontaneous activity in flies. After 60 days of different diets treatment, flies under DR show higher locomotor ability comparing to ad libitum (AL) diet treatment, indicating DR preserves muscle function. We detected dramatic transcriptional upregulation of myofibril genes upon DR in both young and old flies. To assess whether these mRNAs were also translated, we performed translation state array analysis (TSAA), and found increased binding of myosin, troponin, tropomyosin and paramyosin mRNAs to polysomes upon DR. Our data support the idea that DR increases myofibril protein expression which eventually increases muscle mass and slows down age-related sarcopenia progression. Then, we examined the effect of Insulin/IGF signaling, which has been shown to regulate muscle mass, on myofibril protein expression. Muscle-specific expression of dominate negative insulin receptor (InR) decreases DR-dependent myofibril protein expression, while expression of constitutive active InR increase myofibril protein level on DR. Muscle-specific knockdown of myosin or troponin compromised DR-dependent lifespan extension. Furthermore, expression of dominate negative InR in the muscle also shortens lifespan under DR, while dominate negative InR in the muscle shows extended lifespan in AL flies. In summary, DR triggers Insulin/IGF signaling in the muscle to prevent the decline of muscle mass, which is required for DR-dependent lifespan extension.