Abstract
Aging is characterized by a progressive deterioration in physiological functions and metabolic processes. The loss of cells during aging in vital tissues and organs is related to several factors including oxidative stress and inflammation. Skeletal muscle degeneration is common in elderly people; in fact, this tissue is particularly vulnerable to oxidative stress since it requires large amounts of oxygen, and thus, oxidative damage is abundant and accumulates with increasing age. Melatonin (N-acetyl-5-methoxytryptamine) is a highly efficient scavenger of reactive oxygen species and it also exhibits beneficial anti-inflammatory and anti-aging effects. This study investigated the susceptibility of rat L6 skeletal muscle cells to an induced oxidative stress following their exposure to hydrogen peroxide (50 μM) and evaluating the potential protective effects of pre-treatment with melatonin (10 nM) compared to the known beneficial effect of alpha-lipoic acid (300 μM). Hydrogen peroxide-induced obvious oxidative stress; it increased the expression of tumour necrosis factor-alpha and in turn promoted nuclear factor kappa-B and overrode the endogenous defence mechanisms. Conversely, pre-treatment of the hydrogen peroxide-exposed cells to melatonin or alpha-lipoic acid increased endogenous antioxidant enzymes, including superoxide dismutase-2 and heme oxygenase-1; moreover, they ameliorated significantly oxidative stress damage and partially reduced alterations in the muscle cells, which are typical of aging. In conclusion, melatonin was equally effective as alpha-lipoic acid; it exhibited marked antioxidant and anti-aging effects at the level of skeletal muscle in vitro even when it was given in a much lower dose than alpha-lipoic acid.
Highlights
Since individuals in Western societies are living longer, there is an increasing necessity to understand the pathophysiological processes of aging
Myotubes with LA caused the same trend in terms of survival as the melatonin-treated group; in particular, the pre-treatment of L6 cells with LA lowered cell death by 8.8 % (p < 0.05) relative to cell death induced by H2O2 only
We compared the effects of melatonin or LA on atrophy and oxidative stress of cultured rat L6 myotubes exposed to H2O2
Summary
Since individuals in Western societies are living longer, there is an increasing necessity to understand the pathophysiological processes of aging. Aging is associated with the progressive accumulation of oxidative debris, which contributes to functional inefficiency of cells, thereby inducing additional free radical production and metabolic inefficiency. NF-kB, as a transcription factor, stimulates the expression of a AGE (2015) 37: 83 number of genes related to oxidative stress, immune responses, inflammation and apoptosis. It is regulated in a complex manner by the ubiquitin-proteasome system; degradation of the NF-kB inhibitor, IkK, by the proteasome results in activation of NF-kB (Perkins 2007; Skaug et al 2009; Vriend and Reiter 2014)
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