Abstract:  Melatonin, the main secretory product of the pineal gland, is known to collaborate against oxidative stress within cells, but its mechanism of action in terms of stimulating antioxidant enzymes remains unclear. Herein, we propose that melatonin modulates antioxidant enzyme activities via its interaction with calmodulin, which in turn inhibits downstream processes that lead to the inactivation of nuclear RORα melatonin receptor. Eventually, this nuclear transcription factor downregulates NF‐κB‐induced antioxidant enzyme expression. Therefore, the increment in antioxidant enzyme activities induced by melatonin involves the inhibition of the RORα pathway. Thus, in addition to its direct free radical scavenging activities, melatonin has important actions in oxidative defense by stimulating enzymes which metabolize free radicals and radical products to innocuous metabolites.

Endogenous circadian and exogenously driven daily rhythms of antioxidative enzyme activities and of low molecular weight antioxidants (LMWAs) are described in various phylogenetically distant organ...

Abstract: Alzheimer’s disease (AD) is a highly complex neurodegenerative disorder of the aged that has multiple factors which contribute to its etiology in terms of initiation and progression. This review summarizes these diverse aspects of this form of dementia. Several hypotheses, often with overlapping features, have been formulated to explain this debilitating condition. Perhaps the best‐known hypothesis to explain AD is that which involves the role of the accumulation of amyloid‐β peptide in the brain. Other theories that have been invoked to explain AD and summarized in this review include the cholinergic hypothesis, the role of neuroinflammation, the calcium hypothesis, the insulin resistance hypothesis, and the association of AD with peroxidation of brain lipids. In addition to summarizing each of the theories that have been used to explain the structural neural changes and the pathophysiology of AD, the potential role of melatonin in influencing each of the theoretical processes involved is discussed. Melatonin is an endogenously produced and multifunctioning molecule that could theoretically intervene at any of a number of sites to abate the changes associated with the development of AD. Production of this indoleamine diminishes with increasing age, coincident with the onset of AD. In addition to its potent antioxidant and anti‐inflammatory activities, melatonin has a multitude of other functions that could assist in explaining each of the hypotheses summarized above. The intent of this review is to stimulate interest in melatonin as a potentially useful agent in attenuating and/or delaying AD.

In a world in which life expectancy is increasing, understanding and promoting healthy aging becomes a contemporary demand. In the elderly, a sterile, chronic and low-grade systemic inflammation known as “inflammaging” is linked with many age-associated diseases. Considering sarcopenia as a loss of strength and mass of skeletal muscle related to aging, correlations between these two terms have been proposed. Better knowledge of the immune system players in skeletal muscle would help to elucidate their implications in sarcopenia. Characterizing the activators of damage sensors and the downstream effectors explains the inference with skeletal muscle performance. Sarcopenia has also been linked to chronic diseases such as diabetes, metabolic syndrome and obesity. Implications of inflammatory signals from these diseases negatively affect skeletal muscle. Autophagic mechanisms are closely related with the inflammasome, as autophagy eliminates stress signaling sent by damage organelles, but also acts with an immunomodulatory function affecting immune cells and cytokine release. The use of melatonin, an antioxidant, ROS scavenger and immune and autophagy modulator, or senotherapeutic compounds targeting senescent cells could represent strategies to counteract inflammation. This review aims to present the many factors regulating skeletal muscle inflammaging and their major implications in order to understand the molecular mechanisms involved in sarcopenia.

There are several pathologies, syndromes, and physiological processes in which autophagy is involved. This process of self‐digestion that cells trigger as a survival mechanism is complex and tightly regulated, according to the homeostatic conditions of the organ. However, in all cases, its relationship with oxidative stress alterations is evident, following a pathway that suggests endoplasmic reticulum stress and/or mitochondrial changes. There is accumulating evidence of the beneficial role that melatonin has in the regulation and restoration of damaged autophagic processes. In this review, we focus on major physiological changes such as aging and essential pathologies including cancer, neurodegenerative diseases, viral infections and obesity, and document the essential role of melatonin in the regulation of autophagy in each of these different situations.