Is defective electron transport at the hub of aging?

Abstract

SummaryThe bulwark of the mitochondrial theory of aging is that a defective respiratory chain initiates the death cascade. The increased production of superoxide is suggested to result in progressive oxidant damage to cellular components and particularly to mtDNA that encodes subunits assembled in respiratory complexes. Earlier studies of respiration in muscle mitochondria obtained from large cohorts of patients supported this notion by showing that either singly or in combinations, the respiratory complexes exhibited decreased activity in the elderly. The following critique of the most cited publications over the past decade points out the systematic errors that put earlier work at odds with recent findings. These later investigations indicate that aging has no overt effect on either the electron transport system or oxidative phosphorylation.

Bax Regulates Production of Superoxide in Both Apoptotic and Nonapoptotic Neurons: Role of Caspases

“…ROS-induced oxidative stress is implicated in the neuronal damage occurring in ischemia (Abramov et al , 2007), Alzheimer’s disease (Pratico et al , 2001; Lin and Beal, 2006), Parkinson’s disease (Sherer et al , 2003; Keeney et al , 2006), and many other neuronal and nonneuronal pathologies (Halliwell and Gutteridge, 2007). Evidence also suggests that ROS have a role in the degenerative physical transformations occurring in the aging brain and other aging organ systems (Kokoszka et al , 2001; Pollack et al , 2002; Maklashina and Ackrell, 2003; Barja, 2004; Melov, 2004; Miller, 2004). …”

Mitochondrial-nuclear Cross-talk in the Aging and Failing Heart

“…However, these observations have generated some controversy among investigators with some suggesting that the aging heart has either a modest, nonsignificant reduction or no overt effect on either the ETC or OXPHOS function [72,75,86,118] while others found significant alterations in ETC, in which single respiratory complexes were more affected than others, i.e., complex I [30,65], complex IV [88,98] or complex V [19,32]. In our laboratory we have found a modest decrease in complex I and IV activities, and a more severe decline in complex V activity in the hearts of 30-month Fischer 344 rats (unpublished data).…”

Diabetes, Oxidative Stress, Nitric Oxide and Mitochondria Function

“…Mice with increased mitochondria mutation frequency age faster but, somewhat surprisingly, have reduced mitochondria ROS production [205]. However, there are studies showing that older mitochondria have altered morphology and produce more ROS and less ATP [206], but the methods applied in that study is under debate [207]. Also, reduced metabolic rate often results in increased lifespan [208][209][210] even though contradictory reports exist [211].…”