⫸ Melatonin (29) is a neurohormone produced by pineal gland at night. Because of its critical role in adjusting sleep–wake cycles and circadian function, it leads to the wide adoption of primary treatment for sleep disorders and some other conditions. It is evident that melatonin is involved in aging-related processes because we observed that loss of melatonin secretion and decrease in circadian melatonin rhythm amplitude are closely related to differ- ent age-related pathological conditions. Its potential to prolong longevity has been repeatedly described in fruit flies and mice [128–130].

Many studies have shown that it can act as a potent antioxidant that, through its amphiphilic properties, allows it to cross physiological barriers, such as the blood–brain barrier, thereby reducing the level of oxida- tive damage in the aqueous and lipid cell environments. It also characteristically affected the expression of enzymes superoxide dismutase, glutathione peroxidase and cata- lase, and influenced antioxidant activity. In addition, melatonin’s anti-aging effects may be associated with its ability to modulate inflammation and immune responses by activating or inhibiting these processes. The therapeutic effects are thought to be associated with its ability to regulate the nuclear factor erythrocyte 2-associated factor 2, serving as a sensor of oxidative stress, and playing anti-inflammatory roles via antioxidant responses. One of melatonin’s more important abilities in anti-aging research is its potential to treat age-related neurodgenerative diseases such as Alzheimer’s and Parkinson’s. Importantly, the molecular pathways of melatonin action include insulin/IGF-1 pathway, phosphatidylinositol- 3-kinase-protein kinase B/Akt pathway, mTOR pathway, SIRT1 and other molecular pathways related to autophagy and energy metabolism regulation. All these pathways are thought to be major causes of aging and related diseases [131]. ⫷[1]