The Roles of mitochondrial dysfunction and Reactive Oxygen Species in Aging and Senescence

The aging process deteriorates organs' function at different levels, causing its progressive decline to resist stress, damage, and disease. In addition to alterations in metabolic control and gene expression, the rate of aging has been connected with the generation of high amounts of Reactive Oxygen Species (ROS). The essential perspective in free radical biology is that reactive oxygen species (ROS) and free radicals are toxic, mostly cause direct biological damage to targets, and are thus a major cause of oxidative stress. Different enzymatic and non-enzymatic compounds in the cells have roles in neutralizing this toxicity. Oxidative damage in aging is mostly high in particular molecular targets, such as mitochondrial DNA and aconitase, and oxidative stress in mitochondria can cause tissue aging across intrinsic apoptosis. Mitochondria's function and morphology are impaired through aging, following a decrease in the membrane potential by an increase in peroxide generation and size of the organelles. Telomeres may be the significant trigger of replicative senescence. Oxidative stress accelerates telomere loss, whereas antioxidants slow it down. Oxidative stress is a crucial modulator of telomere shortening, and that telomere-driven replicative senescence is mainly a stress response. The age-linked mitochondrial DNA mutation and protein dysfunction aggregate in some organs like the brain and skeletal muscle, thus contributing considerably to these post-mitotic tissues' aging. The aging process is mostly due to accumulated damage done by harmful species in some macromolecules such proteins, DNA, and lipids. The degradation of non-functional, oxidized proteins is a crucial part of the antioxidant defenses of cells, in which the clearance of these proteins occurs through autophagy in the cells, which is known as mitophagy for mitochondria.

Keywords: Aging; Senescence; Mitochondrial dysfunction; Reactive oxygen species.

PMID: 33602082 DOI: 10.2174/1566524021666210218112616