Tumor necrosis factor alpha signaling in skeletal muscle: effects of age and caloric restriction

Past the age of 50 years, aging individuals lose muscle mass at an approximate rate of 1-2% per year. This age-related muscle atrophy, termed sarcopenia, can have significant effects on individual health and quality of life and can also impact the socioeconomic status. Sarcopenia is due to both a decrease in the number of fibers and the atrophy of the remaining fibers. The mechanisms causing loss of fibers have not been clearly defined, but may likely involve apoptosis. Elevated levels of circulating tumor necrosis factor alpha (TNF-alpha) and adaptations in TNF-alpha signaling in aged skeletal muscle may be contributing factors for the activation of apoptosis. These adaptations may be fiber-type specific, which could explain the selective loss of type II fibers, vs. type I fibers, in the aging process. Caloric restriction, a proven antiaging intervention, is known to attenuate the loss of muscle mass and function with age. Furthermore, caloric restriction has been shown to attenuate the age-associated adaptations in TNF-alpha signaling in skeletal muscle, which may be a possible mechanism by which CR prevents apoptosis and the loss of muscle fibers with age. The potential role of TNF-alpha in the progression of sarcopenia will be discussed, as well as the effects of life-long caloric restriction on TNF-alpha signaling.