From mitochondria to sarcopenia: role of 17β-estradiol and testosterone

Abstract

Sarcopenia, characterized by a loss of muscle mass and strength with aging, is prevalent in older adults. Although the exact mechanisms underlying sarcopenia are not fully understood, evidence suggests that the loss of mitochondrial integrity in skeletal myocytes has emerged as a pivotal contributor to the complex etiology of sarcopenia. Mitochondria are the primary source of ATP production and are also involved in generating reactive oxygen species (ROS), regulating ion signals, and initiating apoptosis signals in muscle cells. The accumulation of damaged mitochondria due to age-related impairments in any of the mitochondrial quality control (MQC) processes, such as proteostasis, biogenesis, dynamics, and mitophagy, can contribute to the decline in muscle mass and strength associated with aging. Interestingly, a decrease in sex hormones (e.g., 17β-estradiol and testosterone), which occurs with aging, has also been linked to sarcopenia. Indeed, 17β-estradiol and testosterone targeted mitochondria and exhibited activities in regulating mitochondrial functions. Here, we overview the current literature on the key mechanisms by which mitochondrial dysfunction contribute to the development and progression of sarcopenia and the potential modulatory effects of 17β-estradiol and testosterone on mitochondrial function in this context. The advance in its understanding will facilitate the development of potential therapeutic agents to mitigate and manage sarcopenia.

Serum zinc concentration as a potential predictor of presarcopenia in patients with chronic liver disease: a preliminary study

“…Age-related testosterone decline is associated with the development of sarcopenia ( 32 , 33 ) and, testosterone replacement therapy has been reported to increase muscle strength and lean body mass ( 34 , 35 ). In addition, randomized controlled trials in patients with liver cirrhosis have demonstrated the benefit of testosterone administration ( 36 ).…”

Passive exercise is an effective alternative to HRT for restoring OVX induced mitochondrial dysfunction in skeletal muscle

“…Reduced muscle function is linked to mitochondrial dysfunction ( 38 , 39 ). Mitochondria are critical organelles in skeletal muscle responsible for regulating its metabolic status, including chemical energy (ATP) production, regulation of intracellular Ca 2+ homeostasis, modulation of cell proliferation, and integration of apoptotic signaling ( 40 , 41 ). In the present study, the loss of Ovarian E 2 resulted in diminished ATP production, and WBVT treatment rescued this decline, similar to E 2 therapy.…”

“…The dynamic balance of cellular mitochondrial content is maintained through the opposing processes of mitochondrial biogenesis and mitophagy ( 41 ). The main mitophagy pathway that has been investigated in the context of exercise involves PINK1 and Parkin ( 49 ).…”

Correlation between bone mineral density and sarcopenia in US adults: a population-based study

“…In addition, during our correction for confounding factors in the interaction test for lumbar spine bone density and sarcopenia, we also found a more significant effect of gender on the negative association between lumbar spine bone density and sarcopenia. This may be related to the fact that estrogens, androgens, and testosterone are all associated with the metabolism of skeletal and muscular tissues in humans [ 19 ]. Estrogens maintain skeletal muscle contractility and prevent OP [ 20 ], while androgens and testosterone promote myoblast proliferation [ 21 ].…”