From Chronodisruption to Sarcopenia: The Therapeutic Potential of Melatonin

Abstract

Sarcopenia is an age-related condition that involves a progressive decline in muscle mass and function, leading to increased risk of falls, frailty, and mortality. Although the exact mechanisms are not fully understood, aging-related processes like inflammation, oxidative stress, reduced mitochondrial capacity, and cell apoptosis contribute to this decline. Disruption of the circadian system with age may initiate these pathways in skeletal muscle, preceding the onset of sarcopenia. At present, there is no pharmacological treatment for sarcopenia, only resistance exercise and proper nutrition may delay its onset. Melatonin, derived from tryptophan, emerges as an exceptional candidate for treating sarcopenia due to its chronobiotic, antioxidant, and anti-inflammatory properties. Its impact on mitochondria and organelle, where it is synthesized and crucial in aging skeletal muscle, further highlights its potential. In this review, we discuss the influence of clock genes in muscular aging, with special reference to peripheral clock genes in the skeletal muscle, as well as their relationship with melatonin, which is proposed as a potential therapy against sarcopenia.

Circadian Clock in Muscle Disease Etiology and Therapeutic Potential for Duchenne Muscular Dystrophy

“…Among them, Cry stabilizers such as KL001 [156], Rev-erb agonists such as SR9011 and SR9009 [157], or Rev-erbs antagonist SR8278 [158] have become new chemical probes for clock modulation with potential for drug development. Other molecules, currently in use for sleep disorders or dietary supplements such as melatonin [159][160][161] and nobiletin [162], could be further investigated for potential muscle disease indications. Through high-throughput molecular docking followed by biochemical validations, chlorhexidine (CHX) was identified as a novel clock activator that displays strong promyogenic activities [11].…”