Targeting Mitochondrial Oxidative Stress as a Strategy to Treat Aging and Age-Related Diseases

Abstract

Mitochondria are one of the organelles undergoing rapid alteration during the senescence process. Senescent cells show an increase in mitochondrial size, which is attributed to the accumulation of defective mitochondria, which causes mitochondrial oxidative stress. Defective mitochondria are also targets of mitochondrial oxidative stress, and the vicious cycle between defective mitochondria and mitochondrial oxidative stress contributes to the onset and development of aging and age-related diseases. Based on the findings, strategies to reduce mitochondrial oxidative stress have been suggested for the effective treatment of aging and age-related diseases. In this article, we discuss mitochondrial alterations and the consequent increase in mitochondrial oxidative stress. Then, the causal role of mitochondrial oxidative stress on aging is investigated by examining how aging and age-related diseases are exacerbated by induced stress. Furthermore, we assess the importance of targeting mitochondrial oxidative stress for the regulation of aging and suggest different therapeutic strategies to reduce mitochondrial oxidative stress. Therefore, this review will not only shed light on a new perspective on the role of mitochondrial oxidative stress in aging but also provide effective therapeutic strategies for the treatment of aging and age-related diseases through the regulation of mitochondrial oxidative stress.

Molecular insights into mitoepigenetic stress response signaling in age-associated cardiovascular disease risk

“…NRF2, in response to stress, not only counters mitochondrial ROS by upregulating UCP-3 but also influences mitochondrial biogenesis by sustaining PGC-1α levels and promoting purine biosynthesis [31]. Existing literature supports the role of PGC-1α in promoting the expression of genes necessary for mitochondrial biogenesis [32]. In general, the upkeep of the overall shape within cells relies on well-coordinated cycles of fission and fusion as part of mitochondrial biogenesis.…”

Mitochondria-Targeted Delivery Strategy of Dual-Loaded Liposomes for Alzheimer’s Disease Therapy

“…In addition to oncological diseases [ 52 , 53 , 54 ], the mitochondria-targeted drug delivery strategy is gaining more importance in the context of such disorders as retinal ischemia–reperfusion injury [ 55 ], cardiovascular diseases [ 56 ], stress-related neurodegenerative diseases [ 57 , 58 , 59 ], etc. It is worth noting that in the above cases and in many others, the key role in pathogenesis is played by dysregulation of the production of reactive oxygen species, for which the mitochondria of cells are responsible [ 60 , 61 , 62 ]. Such intense interest in mitochondria as targets for the treatment of various diseases is explained by the fact that mitochondria have a wide range of functions, such as the formation of cell energy units, the control of Ca 2+ homeostasis, the signaling of reactive oxygen species, etc.…”

The Molecular Mechanisms in Senescent Cells Induced by Natural Aging and Ionizing Radiation

“…Oxidative stress arising during mitochondrial dysfunction may be another cause of chronic inflammation [ 158 ]. Oxidative stress activates the secretion of pro-inflammatory cytokines and SASP, including TNF-α, IL-1β, IL-6, and IL-8 [ 159 ]. In particular, ROS act as signalling molecules that induce cytokine activation through various pathways [ 160 ].…”