When considering there are clearly many thousands of studies that one can draw on and that discuss the concept of healthy aging, plus numerous citations that appear related to melatonin in its own right, it is surprising that very few studies examine these topics in tandem to any consistent degree. The scope of the research in this regard, is also limited largely to those dealing with sleep issues, diabetes, cardiovascular disease, and immunity, while far fewer investigations examine melatonin and its impact on skeletal muscle, despite the importance of muscle function and structure for health maintenance and wellbeing in later life.

However, given that inflammation is a core element of aging as well as multiple muscle aging processes 29, according to Jin et al. 21, melatoninapplications may be able to simultaneously protect the mitochondria of skeletal muscle cells that control its physiology, while helping to maintain muscle fiber numbers. Moreover, where required, melatonin might help to partially reverse the prevailing pathological changes of ageing muscle tissue, while restoring or increasing muscle strength capacity in cases suffering from sarcopenia, an age-related disease, which may be due in part to an age-dependent decrease in melatonin secretion 29.

Melatonin and its potential for fostering physical health is also supported by evidence that melatonin is a multi-therapeutic agent that can safely reduce skeletal frailty, muscle atrophy, oxidative stresses, inflammatory processes, ischaemic and non ischaemic cardiovascular conditions, viral infections, diabetes, neurological conditions, cognitions, sleep, and physical performance decrements 152430. As well, melatonin can effectively prevent apoptotic cell death in skeletal muscle fibers via several mechanisms 31, while protecting against muscle related pain, skeletal muscle injury, and oxidative inflammatory damage, in a dose and/or time dependent manner 1532.

Clinically and unsurprisingly, Obayashi et al. 27 who conducted a cross-sectional study of 760 community-based elderly individuals (mean age, 71.0 years) found melatonin secretion was significantly associated with muscle strength in this elderly population. Moreover, in line with findings of Salucci et al. 31 melatonin induced muscle protective effects that were said to include its role in mitigating mitochondrial dysfunction. 

Other data show melatonin can mitigate or prevent

Muscle pathological injury 24

Nerve injuries 24

Abnormal muscle metabolic responses 24

Muscle related microvascular impairments 24

Muscle atrophy/destructive processes 2425

Muscle pain 32

Periarticular muscle damage 33

Muscle fatigue 34

Post-exercise induced muscle injury 35

Muscle inflammation 36

Extra and intracellular oxidative toxicity 373839.

Importantly, this ability to protect muscle from excess damage, which is largely attributable to the favorable impact of melatonin on harmful muscle oxidative processes 373839 is said to prevail even in the context of senescent, diseased or radiated muscle tissue 24. Moreover, although disputed by Armstrup et al. 40 following a double-blind placebo-controlled study of 81 postmenopausal women with osteopenia who received 1 or 3 mg melatonin, or placebo nightly for 12 months, with no observable muscle strength in neither upper- nor lower extremities, Obayashi et al. 27 found melatonin secretion was significantly associated with muscle strength in an elderly population.

Additionally, even though Rondanelli et al. 41 found no strength gains in response to melatonin administration in combination with amino acids in an elderly cohort, Stratos et al. 25, found melatonin not only increased the twitch and tetanic force-generating capacity of injured muscle at days 4, 7, and 14 after baseline in an animal muscle injury model, but the melatonin applications also tended to support muscle restoration and enhanced function after the initially crush induced injury. That is, while the muscle injury caused a large initial reduction in its twitch force capacity when compared to that of the control uninjured muscle, the strength of the muscle improved over the 14 days in response to daily applications of melatonin.

Sayed et al. 36 too noted a beneficial outcome in response to oral melatonin administration applied in an animal model of aging muscle. Not only was the normal muscular architecture preserved, but muscle weight, and muscle fiber numbers as well. In addition, it appeared the melatonin applications prevented mitochondrial damage, tubular aggregation, and apoptotic processes in the aging muscles. Taken together, it was concluded that melatonin can favorably impact aging muscle in multiple ways, a finding supported by others in the context of artificially damaged muscles in animal models 33424344, as well as in association with muscle damage in humans 26. Melatonin also appears to have the potential for regulating muscle regeneration processes 24, increasing the grip force of injured muscle 24, improving muscle healing 24, reducing muscle degenerative processes 24, while fostering general health as well as muscle function in both disabled and aging individuals with severe muscle mass losses, as well as muscle damage 37, injuries, diabetes, and inflammatory diseases 24454647484950.

As well, another important fact concerning melatonin and muscle is that the key metabolic pathways involved in muscle, are found to be impacted favorably by melatonin, due to its ability to prevent mitochondrial dysfunction and insulin resistance, while promoting lipid transport 51. Melatonin also appeared to help attenuate muscle atrophy produced by stroke conditions 52, and showed decreases in older adults with sarcopenia, characterized by muscle mass losses and declining motor function 5354. Melatonin may hence be highly appropriate for helping to avert or compress a multitude of age-related muscular problems and others 3154, while improving functional capacity and energy metabolism that determine life quality perceptions 34415556, even in the face of aging and the presence of chronic health conditions.

In sum, although data on the topic of melatonin and its skeletal muscle associations are fairly limited as outlined by Chen et al. 24, available evidence points to an important role for melatonin in the context of both healthy aging and mobility maintenance, muscle healing, and function due to its multi-dimensional antioxidant, immunomodulatory, bone cell regulation 9, angiogenesis actions 9 and anti-aging properties 57. In turn, the ability to use muscles more proficiently in the presence of melatonin may be an important anti-aging and life prolonging factor in its own right 58, even though Armstrup et al. 40 found no added value of melatonin on muscle strength in older postmenopausal women, as was the case for adult males 59.

The growing older populations worldwide, and the immense challenges these aging individuals may face, has led to discussions about the counter idea of healthy aging and its attainment in efforts to avert immense human and fiscal costs, in spite of evidence that aging is often accepted as a complex multi-factorial process of molecular and cellular decline, that progressively impacts tissue function, causing frailty, susceptibility to disease, and a low life quality. However, even if the idea of healthy aging or aging with limited disability, rather than excess disability is not mainstream or accepted as a possibility by all, an increasing body of recent research not only offers powerful insights into the possibility of achieving more visible signs of healthy aging and longevity, but implies it may be possible to ward off structural and functional deterioration within living systems, at least to some degree, or to delay this 60.

At the same time, the possible utility of melatonin, a multidimensional neuro hormone that tends to decline with age 5, even in healthy older persons 8, has been discussed from both an etiological as well as a therapeutic point of view in this regard ^eg.11. Yet, even though available evidence is generally consistent in viewing melatonin as an important age associated determinant in multiple respects, as observed in 2004 by Karasak et al. 5 available data do not permit any conclusive statements to be made as regards the anti-aging effects of melatonin and its potential for extending normal longevity, years of healthy life, or aspects of this. Its application for purposes of enhancing, protecting, or fostering muscle function under various conditions in particular 24, which has strong support, and is paramount to ensuring late life mobility and wellbeing and limiting disability is rarely discussed in the clinical literature.

This aforementioned due lack of attention is highly surprising because for almost 25 years, or more, and as supported by increasingly sophisticated preclinical studies, melatonin is repeatedly shown to have multiple widespread actions that could potentially either allay, delay, or mitigate multiple analogues of the aging process 57, such as inflammation 24, cell degeneration, declining immunity, circadian and endocrine regulatory effects 6162, plus declining overall health and energy, as well as muscle atrophy, damage, and strength loss effects 24253132496364. In particular, melatonin may be especially helpful in cases where it is vitally important to foster optimal muscle strength recovery following injury 25, while reducing muscle inflammation 32, and muscle atrophy 52. It may specifically prevent muscle mass decreases, and dysfunction attributable to a wide array of common age-associated health challenges such as

Selected neurological diseases

Cancer treatment impacts

Arthritic conditions

Bone diseases

Obesity

Cardiovascular conditions

Diabetes

Hyperthyroidism

Sarcopenia

Cognitive deficits

Peripheral nerve injuries

Muscle disorders and injuries 21246365.

Alternately, a failure to consider the role of melatonin and its widespread influence on body physiology, can predictably induce a wide array of secondary possibly reversible aging outcomes as conceptualized in Figure 1. As well, a failure to screen aging adults for melatonin from an early age, along with efforts to optimize this, as needed, may greatly impact overall health status, profoundly, negatively, and in multiple ways.

In essence, as implied more than 25 years ago by Huether 76, there are strong grounds in our view, based on the above data, in favor of continuing to examine the possible protective role of melatonin in fostering health outcomes across the lifespan, including muscle health, and muscle oxidative processes and mitochondrial integrity 21, as supported by a number of current researchers ^eg.515303544537778. The influence of declining melatonin levels and melatonin receptor alterations across the lifespan also warrants study in this regard. Indeed, in light of the remarkable promise of melatonin in the context of aging and health maintenance, frailty, falls risk, and muscle weakness alone, a significant return on such an investment can undoubtedly be anticipated with a high degree of confidence, when compared to the costs of failing to act.