Short‐Term Caloric Restriction and Sites of Oxygen Radical Generation in Kidney and Skeletal Muscle Mitochondria

Abstract

Mitochondrial free radical generation is believed to be one of the principal factors determining aging rate, and complexes I and III have been described as the main sources of reactive oxygen species (ROS) within mitochondria in heart, brain, and liver. Moreover, complex I ROS generation of heart and liver mitochondria seems especially linked to aging rate both in comparative studies between animals with different longevities and in caloric restriction models. Caloric restriction (CR) is a well-documented manipulation that extends mean and maximum longevity. One of the factors that appears to be involved in such life span extension is the reduction in mitochondrial free radical generation at complex I. We have performed two parallel investigations, one studying the effect of short-term CR on oxygen radical generation in kidney and skeletal muscle (gastrocnemius) mitochondria and a second one regarding location of mitochondrial ROS-generating sites in these same tissues. In the former study, no effect of short-term caloric restriction was observed in mitochondrial free radical generation in either kidney or skeletal muscle. The latter study ruled out complex II as a principal source of free radicals in kidney and in skeletal muscle mitochondria, and, similar to previous investigations in heart and liver organelles, the main free radical generators were located at complexes I and III within the electron transport system.

The hydrogen sulfide signaling system: changes during aging and the benefits of caloric restriction

“…Additionally, H 2 S may also react with, and be quenched by, increased superoxide (Geng et al 2004a) as well as increased peroxynitrite produced from the reaction of NO with superoxide (Whiteman et al 2004). CR has been proposed to reduce age-related endothelial dysfunction by reducing the increase in superoxide production associated with aging, thereby maintaining a more youthful state (Barja 2002;Castello et al 2005;Gredilla et al 2004;Gredilla et al 2001;Taddei et al 2006). Consistent with the beneficial effects of CR, the expression of CSE and to a lesser extent CBS did not significantly increase with age in CR animals.…”

“…Caloric restriction (CR) is an intervention that attenuates many effects of aging (Anderson and Weindruch 2010;Labinskyy et al 2006;Leeuwenburgh and Prolla 2006), including cardiovascular morbidity (van der Loo et al 2000), cross-linking of cardiac and skeletal muscle proteins (Leeuwenburgh et al 1997), mitochondrial dysfunction (Aspnes et al 1997;Payne et al 2003), loss of skeletal muscle mass (Payne et al 2003;van der Loo et al 2000), and endothelial dysfunction (Barja 2002;Castello et al 2005;Gredilla et al 2004;Gredilla et al 2001;Taddei et al 2006). Furthermore, CR attenuates the age-related impairment of the NO signaling system (Minamiyama et al 2007;Sharifi et al 2008;Yang et al 2004).…”

Lifelong exercise and mild (8%) caloric restriction attenuate age-induced alterations in plantaris muscle morphology, oxidative stress and IGF-1 in the Fischer-344 rat

“…Moderate (e.g., 40%) caloric restriction for 12 or 18 months consistently reduces oxidative stress and increases lifespan in rodents Lopez-Torres et al, 2002). Long-term caloric restriction attenuates the age-induced elevation in production of reactive oxygen species (ROS) by mitochondria and oxidative damage to mitochondrial DNA (mtDNA), while short-term caloric restriction does not (Gredilla et al, 2001(Gredilla et al, , 2004). Short-term caloric restriction has only a modest to little effect on mitochondrial ROS production (Bevilacqua et al, 2005;Gredilla et al, , 2004.…”

“…Long-term caloric restriction attenuates the age-induced elevation in production of reactive oxygen species (ROS) by mitochondria and oxidative damage to mitochondrial DNA (mtDNA), while short-term caloric restriction does not (Gredilla et al, 2001(Gredilla et al, , 2004). Short-term caloric restriction has only a modest to little effect on mitochondrial ROS production (Bevilacqua et al, 2005;Gredilla et al, , 2004. Long-term, moderate caloric restriction is effective in increasing rodent and rhesus monkey lifespan and protecting against age-induced sarcopenia, but may be difficult to maintain long-term in humans due to adverse health effects (Dirks and Leeuwenburgh, 2006).…”

Caloric restriction and redox state: Does this diet increase or decrease oxidant production?

“…[51][52][53] Another large body of work demonstrates that ROS release from mitochondria or tissues from CR animals is decreased. 37,[53][54][55][56][57][58][59][60][61][62][63][64][65][66][67] Other publications found no changes in ROS production with CR 46,[68][69][70][71] and many propose that CR-induced decreases in ROS release depend on tissues examined, time on the diet, animal age when the diet was initiated, and gender. No experimental publication was located demonstrating that CR in rodents enhances ROS generation in non-inflammatory tissues.…”