Monoamine oxidases in age-associated diseases: New perspectives for old enzymes

•Monoamine oxidases overactivation is a common hallmark of several age-associated diseases.•Monoamine oxidases are involved in neurodegenerative diseases, cardiac aging, metabolic disorders and cancer, for which selective inhibitors are currently used or in development.•Increased monoamine oxidase activity leads to altered substrate (norepinephrine, dopamine, serotonin) concentrations and generates oxidative stress and aldehydes during aging.•Monoamine oxidase-dependent byproducts cause protein aggregation, cell death, mitochondrial oxidative damage and impair the different steps of mitochondrial quality control such as mitochondrial biogenesis, dynamics and autophagy in the central nervous system and the heart. Population aging is one of the most significant social changes of the twenty-first century. This increase in longevity is associated with a higher prevalence of chronic diseases, further rising healthcare costs. At the molecular level, cellular senescence has been identified as a major process in age-associated diseases, as accumulation of senescent cells with aging leads to progressive organ dysfunction. Of particular importance, mitochondrial oxidative stress and consequent organelle alterations have been pointed out as key players in the aging process, by both inducing and maintaining cellular senescence. Monoamine oxidases (MAOs), a class of enzymes that catalyze the degradation of catecholamines and biogenic amines, have been increasingly recognized as major producers of mitochondrial ROS. Although well-known in the brain, evidence showing that MAOs are also expressed in a variety of peripheral organs stimulated a growing interest in the extra-cerebral roles of these enzymes. Besides, the fact that MAO-A and/or MAO-B are frequently upregulated in aged or dysfunctional organs has uncovered new perspectives on their roles in pathological aging. In this review, we will give an overview of the major results on the regulation and function of MAOs in aging and age-related diseases, paying a special attention to the mechanisms linked to the increased degradation of MAO substrates or related to MAO-dependent ROS formation.