This popular science article covers some of the major research topics related to sarcopenia, the loss of muscle mass and strength that occurs with age. A great deal is known of the biochemistry of muscle aging, the signals and mechanisms involved in muscle stem cell activity and muscle growth, and how they change with age. A great deal more remains to be discovered, and fitting together what is already known into a coherent whole is a still a work in progress. Any proposed layering of cause and effect is speculative at best, and it is usually unclear as to where exactly any newly described signal or mechanism fits. It it is probably the case, here as elsewhere, that the fastest path to improved knowledge is to start in on manipulating the aging of muscle: adjust a mechanism in isolation of the others and analyze the results.
Up to a quarter of adults over the age of 60 and half of those over 80 have thinner arms and legs than they did in their youth. The good news is that exercise can stave off and even reverse muscle loss and weakness. Recent research has demonstrated that physical activity can promote mitochondrial health, increase protein turnover, and restore levels of signaling molecules involved in muscle function. But while scientists know a lot about what goes wrong in aging, and know that exercise can slow the inevitable, the details of this relationship are just starting to come into focus.
Mature muscle fibers are post-mitotic, meaning they do not divide anymore. As a result, in adulthood both muscle growth and repair are made possible only by the presence of muscle stem cells known as satellite cells. Elderly human satellite cells show dramatic changes in their epigenetic fingerprint. One gene, called sprouty 1, is known to be an important regulator of cell quiescence. Reduced sprouty 1 expression can limit satellite cell self-renewal and may partially explain the progressive decline in the number of satellite cells observed in human muscles during aging. Indeed, stimulation of sprouty 1 expression prevents age-related loss of satellite cells and counteracts age-related degeneration of neuromuscular junctions in mice.
Other likely culprits of muscle aging are the mitochondria, the powerhouses of muscle. To work efficiently, skeletal muscle needs a sufficient number of fully functional mitochondria. These organelles represent around 5 percent to 12 percent of the volume of human muscle fibers, depending on activity and muscle specialization (fast-twitch versus slow-twitch). And research suggests that abnormalities in mitochondrial morphology, number, and function are closely related to the loss of muscle mass observed in the elderly.
In 2005, researchers combined the circulation of young and old mice and found that factors in the blood of young mice were able to rejuvenate muscle repair in aged mice. It is now well known that the levels of circulating hormones and growth factors drastically decrease with age and that this has an effect on muscle aging. Indeed, hormone replacement therapy can efficiently reverse muscle aging, in part by activating pathways involved in protein synthesis. Moreover, the muscle itself is a secretory endocrine organ. Myokine proteins produced by the muscle when it contracts can act locally on muscle cells or other types of cells such as fibroblasts and inflammatory cells to coordinate muscle physiology and repair, or they can have effects in distant organs, such as the brain.
Although several of these myokines have been identified-in culture, human muscle fibers secrete up to 965 different proteins-researchers have only just begun to understand their role in muscle aging. The first myokine to be identified, interleukin-6 (IL-6), participates in muscle maintenance by decreasing levels of inflammatory cytokines in the muscle environment, while increasing insulin-stimulated glucose uptake and fatty-acid oxidation.
Researchers recently discovered a novel myokine, which they termed apelin. The researchers have demonstrated that this peptide can correct many of the pathways that are deregulated in aging muscle. When injected into old mice, apelin boosted the formation of new mitochondria, stimulated protein synthesis, autophagy, and other key metabolic pathways, and enhanced the regenerative capacity of aging muscle by increasing the number and function of satellite cells. Levels of circulating apelin declined during aging in humans, suggesting that restoring apelin levels to those measured in young adults may ameliorate sarcopenia.