Oxidative damage and mitochondrial decay in aging.

Abstract

We argue for the critical role of oxidative damage in causing the mitochondrial dysfunction of aging. Oxidants generated by nito dria appear to be the major source of the oxidative lesions that accumulate with age. Several mitochondrial fumctins decline with age. The contributing factors include the intrinsic rate of proton leakage across the inner mitochondrial membrane (a correlate of oxidant formation), decreased membrane fluidity, and decreased levels and function of cardiolipin, which supports the function of many of the proteins of the inner mitochondrial membrane.

Methylene blue alleviates nuclear and mitochondrial abnormalities in progeria

“…It is agreed that cumulative oxidative damages by ROS is one of the causes of normal aging (Shigenaga et al ., 1994). The majority of ROS is generated inside of mitochondria, and dysfunctional mitochondria will directly and indirectly elevate ROS production (Lin & Beal, 2006; Chen et al ., 2007).…”

“…Mitochondria are complex organelles that are believed to play a significant role in biological aging (Shigenaga et al ., 1994; Bratic & Larsson, 2013). They form a sophisticated, dynamic, and tubular network that moves along microtubules and actin fibers (Morris & Hollenbeck, 1995; Nunnari & Suomalainen, 2012).…”

Bcl-2 family members inhibit oxidative stress-induced programmed cell death in Saccharomyces cerevisiae

“…Oxidative stress has been implicated in numerous biological processes and diseases, including cancer, tumor promotion, arthritis, heart disease, aging, and programmed cell death in both plants and animals [1][2][3][4]. Thus, aerobic organisms need to mitigate the deleterious reactive oxygen species (ROS) that are generated during the normal course of aerobic metabolism to avoid oxidative damage.…”

Native‐DIGE: A new look at the mitochondrial membrane proteome

“…These superstructures confer several advantages including substrate channeling and stabilization of individual complexes, executing higher efficiency of electron transport and minimizing the proton leak [4][5][6]. Aging-associated mitochondrial dysfunction is evidenced by decline in activities of all respiratory chain complexes, an observation also common for various neurodegenerative diseases caused by oxidative stress [2,7]. Comparison of mitochondrial proteomes of various model organisms has revealed a noticeable, aging-induced decrease at expression levels of different subunits of ATP synthase and cytochrome c oxidase [8].…”

“…It is therefore necessary to consider the abundance changes in proteins in context of protein-protein interactions.Any change at expression level of genes or proteins, besides post-translational protein modifications, imposes significant impact on up-/down-regulation of the mitochondrial system. Mitochondrial dysfunctions often initiate the signaling pathways of cellular senescence and premature cell death, characteristic of several aging-associated neurodegenerative diseases [2].…”