FIGURE 6-4 A decline in fractional muscle mitochondrial protein synthesis occurred with age. Approximately a 40 percent decline occurred by middle age (P < 0.01), but there was no further decline with advancing age. ** Indicates significant difference from young age. Source: Rooyackers, O.E., D.B. Adey, P.A. Ades, and K.S. Nair. 1996. Effect of age on in vivo rates of mitochondrial protein synthesis in human skeletal muscle. Proc. Natl. Acad. Sci. USA 93:15364-15369. Copyright 1996 National Academy of Sciences, U.S.A.

(such as myosin heavy chain and mitochondrial proteins) occurs with age (Balagopal et al., 1997; Rooyackers et al., 1996; Welle et al., 1993; Yarasheski et al., 1993), perhaps reflecting the inability of mitochondria to produce sufficient ATP. Furthermore, recent studies have demonstrated that synthesis rates of myosin heavy chain, a major myofibrillar protein involved in hydrolysis of ATP and conversion of chemical energy from ATP to mechanical energy, also decline by middle age (Balagopal et al., 1997). These results suggest that the aging process selectively affects the ATP-generating machinery of muscle and imply that any intervention should seek to restrict this loss of mitochondrial capacity. In addition, the reduced synthesis rate of myosin heavy chain is compatible with the notion that the ability to maintain adequate muscle protein quality declines with age, thereby potentially compromising the efficiency of the locomotive apparatus to extract mechanical energy from fuel stores. As discussed below, it is likely that age associated decrements in circulating levels of anabolic hormones, such as growth hormone (GH), insulin-like growth factor I (IGF-I), sex steroids, and fading effectiveness of insulin are all involved in the involution of muscle that occurs with aging.