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Causes & Mechanisms

A Muscle Metabolic Imbalance Caused by Multiple Factors

Sarcopenia is a geriatric syndrome associated with metabolic imbalance or a loss of metabolic homeostasis in skeletal muscle. The complex multifactorial mechanisms overlap the aging process, although it is accelerated compared to the normal aging process. Because of genetic and epigenetic changes in myogenicity, neurogenicity, endocrinal system and its sensitivities, mitochondrial morphology, and humoral immunity, metabolic homeostasis in skeletal muscle is altered at each stage from cell turnover to performance.

As mentioned above, sarcopenia mimics the aging process. But it is progressively accelerated because of lifestyle and other issues, comparing to the normal aging. It is known that a sedentary lifestyle and nutritional deficiency directly havserious impacts on sarcopenia.


Adequate exercise is essential to healthy muscle metabolism. However, hurdles to adequately exercising higher during aging, and even more with sarcopenia. Exercise capacity is becoming lower, which make it more difficult to practice already onerous exercise. Further, the sensitivity or adaptation to exercise also becomes lower.


Nutrition from the diet is another critical factor to accelerate the process. In many cases, some nutritional deficiencies are observed in patients with sarcopenia. Intake of enough quality protein is a fundamental to muscle synthesis. Amino acid, especially branched chain amino acid (BCAA) is a key to promote muscle synthesis and maintain quality of muscle. Vitamin D is also critical to maintain protein metabolic balance in muscle. Any deficit in such essential micronutrients results in enhancing sarcopenia. Further, it is pointed out that intake of an efficacious combination of antioxidants is important in order to address elevated levels of excessive oxidative stress and inflammation during aging and even more in sarcopenia.

Physical and Nutritional Deficiency Accelerates the Pathological Process

Muscle Quality Deteriorates as well as Mass

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When considering about the impact of sarcopenia, it is important to pay attention to not only decreased muscle mass but also a loss of muscle quality, including concepts of decreased specific force (strength per muscle mass unit) or neuromuscular junction. It is a fact that a decrease in muscle strength and/or physical performance is known to be in-linear with a decrease in muscle mass. In the FNIH-NIA-FDA Sarcopenia Consensus Summit which was held in 2012, it was confirmed that muscle quality is important and that its decrease can be affected not necessarily by muscle mass in sarcopenia, regardless of the traditional view that sarcopenia is muscle mass loss.

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Mitochondrial Play Important Roles in Functional Decline

Mitochondria lose their energetics during aging even more in sarcopenia. Some geriatric researchers have hypothesized that a decline in mitochondrial energetics plays a main role in sarcopenia. As mentioned above, a decline in muscle function and mobility is, in many cases, greater than that expected from the magnitude of muscle mass loss. It can be due to mitochondrial dysfunction.


It has been heavily debated that decreased metabolic integrity of mitochondria leads to a loss of mobility mediating a decline in muscle quality. Some studies reported that it is associated to the neuromuscular junction (NMJ) remodeling during aging. A loss of integrity of NMJ alters mitochondrial morphology, which decreases enzymatic activities and calcium Ca2+ buffering in mitochondria.

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