Sarcopenia Skeletal Muscle Aging

Sarcopenia, the Skeletal Muscle as an Endocrine Organ and Aging

Sarcopenia – Aging

In a recent review, Drs. A. Pratesi, F. Tarantini and M. Di Bari discuss major hormonal and immune mechanisms that drive the age-related decline in muscle quantity and quality. Besides the hormonal factors, the authors outline the role of some skeletal muscles mediators, termed ‘myokines’ that act in an autocrine, paracrine, or ‘hormone-like’ fashion. This includes interleukin (IL)-6, IL-8, IL-15, Brain-Derived Neurotrophic Factor (BDNF), and Leukemia Inhibitory Factor (LIF).

The decrease in skeletal muscle mass, by 3-8 % per decade after the age of 30 years, is recently referred to as sarcopenia. Since the mid-’90s, the age-related “lack of flesh” has been termed sarcopenia, which indicates a deterioration in muscle quantity and quality leading to a gradual slowing of movement, a decline in strength and power, and an increased risk of falls and fall-related injuries.

This condition typically accelerates around age 75, and is a factor in the occurrence of frailty and the likelihood of falls and fractures, functional disability, decreased bone density, glucose intolerance, and decreased heat and cold tolerance in older adults. Sarcopenia is considered a risk factor for physical disability, independent of age, ethnicity, obesity, socioeconomic status, morbidity, and health behaviors.

It has been known for decades that excessive glucocorticoids and thyroid hormones, as well as diminished testosterone, estrogen, and growth hormone, lead to muscle atrophy. Recent evidence indicates that skeletal muscles produce a variety of molecules, denominated “myokines”, which act in an autocrine, paracrine, or endocrine hormone-like fashion.

Interleukin-6, a cytokine quite often considered a pro-inflammatory mediator or ‘hormone’ was the first cytokine to be proposed as a myokine by Pedersen et al. in 2003. In the year 2000 it was observed that IL-6 plasma levels increase with exercise, but only subsequent research highlighted that muscle-derived IL-6 is an important player in metabolism. Interestingly, it seems that contraction-induced production of IL-6 by skeletal muscles might display anti-inflammatory effects.

Recent research suggests that this myokine is able to suppress IL-1 and TNF-alpha synthesis and stimulate production of IL-1ra and IL-10. Also of note, evidence, as discussed in this review, indicates that muscle activity might improve lipid metabolism and reduce visceral fat. This, in turn, may reduce the risk of cardiovascular diseases, diabetes mellitus, dementia, and some types of cancer, due at least in part by stimulating the production of BDNF and IL-15.

diseasoma physical inactivityFigure 1. The pathogenic hypothesis of “diseasoma of physical inactivity”. Modified from Pedersen BK, et al.

Why might this research have important clinical implications? Systemic low-grade inflammation has been implicated in the pathogenesis of atherosclerosis, insulin resistance, tumor growth, and neurodegeneration. Thus, according to the authors Drs. A. Pratesi, F. Tarantini and M. Di Bari it has been hypothesized that inflammation plays a causal role in the functional decline associated with aging, at least in part, through sarcopenia.

Of note, low-grade inflammation has also been associated with frailty, defined as a multi-system impairment with increased vulnerability to stress in old age, distinct from, although inter-related with, comorbidity and disability.

Taken together, the available evidence indicates that muscle activity would improve lipid metabolism and reduce visceral fat, thus ultimately reducing the risk of cardiovascular diseases, diabetes mellitus, dementia, and some types of cancer, at least in part by stimulating the production of BDNF and IL-15.

In conclusion, the authors of this review summarized some recent evidence suggesting that a major component of the aging phenotype may be explained by an imbalance between inflammatory and anti-inflammatory networks, resulting in the low-grade, chronic pro-inflammatory status. Systemic low-grade inflammation, defined as two-to four-fold elevation in circulating levels of pro-inflammatory and anti-inflammatory cytokines, appears to contribute to the development of atherosclerosis, insulin resistance, tumor growth, and neurodegeneration.

Source: Clin Cases Miner Bone Metab, 2013; 10:11-4. doi: 10.11138/ccmbm/2013.10.1.011

Read more: Clin Cases Miner Bone Metab

Cover image credit: Aging of skeletal muscle is central in the pathogenesis of immune senescence and sarcopenia. Multiple pathways are affected, including insufficient myokine signalling (IL-6, IL-7, IL-15), shifting of membrane bound immune regulatory factors towards a pro-inflammatory profile, impaired immune cell function and altered body composition. From: Skeletal muscle as potential central link between sarcopenia and immune senescence, by Christopher Nelke, Rainer Dziewas, Jens Minnerup, Sven G Meuth, Tobias Ruck, EBioMedicine, 2019 Nov;49:381-388. doi: 10.1016/j.ebiom.2019.10.034. Open access, Public domain.