From the perspective of systems biology,
melatonin is relevant to aging in multiple ways. As a highly pleiotropic agent, it acts as a modulator and protectant of mitochondrial electron flux, a potent
antioxidant that supports the redox balance and prevents excessive
free radical formation, a coregulator of metabolic sensing and antagonist of
insulin resistance, an immune modulator, a physiological
hypnotic and, importantly, an orchestrating chronobiotic. It entrains central and peripheral circadian clocks and is required for some high-amplitude rhythms. The circadian system, which controls countless functions, is composed of many cellular oscillators that involve various accessory
clock proteins, some of which are modulated by
melatonin, e.g.
sirtuin 1,
AMP-dependent
protein kinase, and
protein kinase Cα. Aging and age-related diseases are associated with losses in
melatonin secretion and rhythm amplitudes. The dynamic properties of aging processes deserve particular attention. This concerns especially two vicious cycles, one of
peroxynitrite formation driven by
inflammation or overexcitation, another one of inflammaging driven by the senescence-associated secretory phenotype, and additionally the loss of dynamics in a deteriorating circadian multioscillator system.