Sarcopenia of aging: Underlying cellular mechanisms and protection by calorie restriction

Abstract

Sarcopenia, the loss of muscle mass and function, is a common feature of aging and impacts on individual health and quality of life. Several cellular mechanisms have been involved in the pathogenesis of this syndrome, including mitochondrial dysfunction, altered apoptotic and autophagic signaling, and, more recently, trace metal dyshomeostasis. Calorie restriction (CR) without malnutrition has been shown to ameliorate the age-related loss of muscle mass in a variety a species. Mechanisms of protection span from preservation of mitochondrial functional and structural integrity to mitochondrial biogenesis, reduction of oxidative stress, and favorable modulation of apoptotic and autophagic signaling pathways. Importantly, preliminary evidence indicates that moderate CR may promote muscle mitochondrial biogenesis in middle-aged human subjects. Further research is warranted to investigate whether CR may represent a safe and efficient strategy to delay the onset and mitigate the progression of sarcopenia in older adults.

Role of dietary amino acid balance in diet restriction‐mediated lifespan extension, renoprotection, and muscle weakness in aged mice

“…Whether there is a beneficial effect of DR on muscle function has been controversial to date, because whereas some studies have shown that DR improves muscle function (Marzetti, Lees, Wohlgemuth, & Leeuwenburgh, 2009; McKiernan et al., 2012), another showed it had the opposite effect (Lopes et al., 1982). Our results demonstrate that DR can improve slow‐twitch muscle fiber function, along with the maintenance of muscle fiber size.…”

Multiple Pathways to the Same End: Mechanisms of Myonuclear Apoptosis in Sarcopenia of Aging

“…In another very recent study, the age-dependent increase in TNF-α apoptotic signaling was paralleled by decreased expression of the antiapoptotic interleukin 15 (IL-15) and its specific receptor subunit α (IL-15Rα) in the rat gastrocnemius muscle [20]. In contrast, lifelong calorie restriction (CR), an intervention known to attenuate apoptosis in the skeletal muscle of old rodents [69], preserved IL-15 signaling and muscle mass into very old age, while preventing the activation of the death receptor–mediated apoptosis [20]. These findings suggest that the loss of the anabolic drive by IL-15 may unbridle the proapoptotic actions of TNF-α in skeletal muscle, thus contributing to the development of sarcopenia and loss of physical function in old age.…”

Accelerated aging phenotype in mice with conditional deficiency for mitochondrial superoxide dismutase in the connective tissue

“…These pathological states share unique features and are all characterized by a loss of collagen type I, dysregulated fibroblast-matrix interactions and impaired fibroblast interactions with organ parenchyma, mainly with organ-specific epithelial cells and muscle (Wenk et al, 1999(Wenk et al, , 2004Krtolica & Campisi, 2002;Campisi, 2005;Labat-Robert & Robert, 2007;Treiber et al, 2009). A variety of genetic and environmental factors including increased concentration of ROS, mitochondrial dysfunction (Hiona & Leeuwenburgh, 2008), changes in autocrine, paracrine and endocrine release of hormones, growth factors (Perrini et al, 2010) and cytokines (Coppe et al, 2008) have been identified to contribute to skin aging, sarcopenia and osteoporosis in humans and rodents (Zofkova, 2003;Raisz, 2005;Ralston & de Crombrugghe, 2006;Hiona & Leeuwenburgh, 2008;Marzetti et al, 2009). Research on the regulation of connective tissue organization by enhanced release of ROS from mitochondria during fibroblast aging is a matter of increasing interest and relevance as it may provide ultimate clues for mechanisms underlying disruption of connective tissue homoeostasis in aging-related skin atrophy, sarcopenia and osteoporosis.…”