Mitochondria: multifaceted regulators of aging

Abstract

Aging is accompanied by a time-dependent progressive deterioration of multiple factors of the cellular system. The past several decades have witnessed major leaps in our understanding of the biological mechanisms of aging using dietary, genetic, pharmacological, and physical interventions. Metabolic processes, including nutrient sensing pathways and mitochondrial function, have emerged as prominent regulators of aging. Mitochondria have been considered to play a key role largely due to their production of reactive oxygen species (ROS), resulting in DNA damage that accumulates over time and ultimately causes cellular failure. This theory, known as the mitochondrial free radical theory of aging (MFRTA), was favored by the aging field, but increasing inconsistent evidence has led to criticism and rejection of this idea. However, MFRTA should not be hastily rejected in its entirety because we now understand that ROS is not simply an undesired toxic metabolic byproduct, but also an important signaling molecule that is vital to cellular fitness. Notably, mitochondrial function, a term traditionally referred to bioenergetics and apoptosis, has since expanded considerably. It encompasses numerous other key biological processes, including the following: (i) complex metabolic processes, (ii) intracellular and endocrine signaling/communication, and (iii) immunity/inflammation. Here, we will discuss shortcomings of previous concepts regarding mitochondria in aging and their emerging roles based on recent advances. We will also discuss how the mitochondrial genome integrates with major theories on the evolution of aging.

Cerebral Mitochondrial Function and Cognitive Performance during Aging: A Longitudinal Study in NMRI Mice

“…In 1979, mitochondria were identified as the key producer of ROS that significantly contribute to aging processes [18][19][20][21]. However, low "physiological" ROS levels are known to have important functions for signaling mechanisms in the cell [22]. Under physiological conditions, the antioxidative defense system, including superoxide dismutase (SOD) and the glutathione (GSH) system, is able to eliminate highly reactive molecules [23].…”

Gypenoside Inhibits Endothelial Cell Apoptosis in Atherosclerosis by Modulating Mitochondria through PI3K/Akt/Bad Pathway

“…Mitochondria are a major cellular organelle involved in cell growth, differentiation, message transmission, apoptosis, and energy supply [36]. 95% of the energy required for cell survival is provided by the mitochondrial respiratory chain [37].…”

Improvement of cognitive and motor performance with mitotherapy in aged mice

“…Studies in various organisms, such as nematodes, Drosophila, rodents, and humans, have strongly supported that aging is closely associated with mitochondrial dysfunction [ 2 , 3 ]. Thus, protection of the mitochondrial structure or stimulation of mitochondrial function is considered as practical ways in anti-aging [4,5]. However, since most of the mitochondrial damage is irreversible during aging process, the agents can always provide limited protection.…”