We have shown that age-related loss of muscle mass, or sarcopenia, is delayed and possibly prevented, in our rhesus monkey model of adult-onset, moderate DR. To our knowledge this is the first report of DRs ability to maintain muscle mass in aging animals from a primate species. If translatable to humans, this result could have major positive effects on functionality and quality of life for elderly people, as well as on lowering healthcare expenditures.
The etiology of sarcopenia is not well understood and is most likely a multifactorial process. Many theories have been advanced including, but not limited to, changes at the cellular level such as a reduction in muscle cell number, decreased muscle twitch time and force, muscle fiber atrophy, and decreased satellite cell recruitment [17
]. Biochemical and metabolic changes in skeletal muscle related to mitochondrial DNA deletion mutations are also present with sarcopenia [21
], and in rodents, these deletion mutations can be attenuated by DR [24
]. Additionally, central and peripheral nervous system innervation and decreased dietary protein intake are also likely to be involved in the progression of sarcopenia [17
]. More recent evidence points to the potential roles of apoptosis [25
] and inflammation [18
] in the etiology of sarcopenia.
The plethora of endocrine changes that occur during the aging process are also likely involved in the development and progression of sarcopenia. For example, several studies have shown that replacement of testosterone to young normal levels resulted in modest increases in muscle mass and muscle strength [33
] however, not all studies report a positive effect of testosterone supplementation [37
]. Additionally, insulin has been shown to mediate muscle protein synthesis [38
] and in the pre-insulin era diabetes was associated with severe muscle wasting.
The results presented in this report for the rhesus monkey are similar to previous findings in a rodent model. In the long-lived Fischer X Brown Norway F1 hybrid rat, ad libitum
fed animals lost significant muscle mass (dissected mass of vastus lateralis
, rectus femoris
) between 21 and 36 months of age, and this loss was retarded, but not prevented by DR [24
]. McKiernan and colleagues further found that significant muscle fiber loss and atrophy of type II muscle fibers contributed to sarcopenia in the aged ad libitum fed animals, and that DR animals conserved muscle fiber number with advancing age, however DR did not prevent type II muscle fiber atrophy [24
Our results are from a noninvasive imaging technique that is not able to address issues of muscle fiber loss or atrophy. We are currently conducting studies that will address the effects of DR at the level of the individual muscle fiber. However, given our previous findings of sarcopenia, both by in vivo
DXA and ex vivo
muscle mass, in ad libitum
fed rhesus monkeys [12
] we are confident that results from the muscle fiber analysis will be consistent with the DXA findings presented here. Additionally, although there appears to be a clear relationship between muscle mass and muscle strength that further translates into functionality, techniques to test muscle strength in rhesus monkeys have yet to be developed. We continue to explore potential methods for this assessment. Despite these limitations, we have presented strong evidence of a beneficial effect of DR on a natural and universal process of physiological deterioration. These findings have significant implications for human health, quality of life and healthcare expenditures.