Effect of 8.5% and 25% caloric restriction on mitochondrial free radical production and oxidative stress in rat liver

Abstract

Previous studies have consistently shown that 40% caloric restriction (CR) decreases the rate of mitochondrial ROS production and steady-state levels of markers of oxidative damage to macromolecules including mitochondrial DNA. However, few investigations have studied whether these changes also occur in lower CR regimes. This is of potential interest since moderate levels of dietary restriction are more practicable for humans. In this investigation male Wistar rats were subjected to 8.5% and 25% caloric restriction. Neither 8.5% nor 25% CR changed mitochondrial ROS production, oxygen consumption or mtDNA oxidative damage in rat liver mitochondria. However, both 8.5% and 25% CR significantly decreased the five different markers of protein oxidation, glycoxidation and lipoxidation measured, aminoadipic and glutamic semialdehyde, carboxyethyl-lysine, carboxymethyl-lysine, and malondialdehyde-lysine. The fatty acid composition of liver mitochondria was also affected and led to a moderate decrease in the degree of membrane unsaturation in both 8.5% and 25% CR. While 8.5% CR only affected complex I concentration (which was decreased), 25% CR decreased complexes I and IV and increased complexes II and III of the respiratory chain. Apoptosis-inducing factor (AIF) significantly decreased in 25% CR but not in 8.5% CR. The results show that moderate levels of caloric restriction can have beneficial effects including decreases in oxidative protein modification and a lower sensitivity of membranes to lipid peroxidation, in association with a reprogramming of the respiratory chain complexes and AIF content.

Forty percent and eighty percent methionine restriction decrease mitochondrial ROS generation and oxidative stress in rat liver

“…Previous studies have consistently shown that DR decreases mitROS generation and oxidative damage (reviewed in Gredilla and Barja 2005), and that these changes can be reproduced by PR independently of caloric restriction (Sanz et al 2004;Gómez et al 2007;Ayala et al 2007), but not by lipid (Sanz et al 2006a) or carbohydrate (Sanz et al 2006b) restriction. In a longevity study in rats it was found that that DR almost totally prevents rat nephropathy involving glomerular sclerosis, and that ''DR without PR'' also produced this although somewhat less than DR, meaning that a small effect of PR should be involved in that protection against renal disease (Masoro et al 1989).…”

“…Thus, whereas neither lipid restriction (Sanz et al 2006a) nor carbohydrate restriction (Sanz et al 2006b) change mitROS production, protein restriction (PR) (Sanz et al 2004) decreases mitROS generation and oxidative stress in rat liver in a way quantitatively and qualitatively similar to that induced by DR. These decreases were specifically related to the lowered protein ingestion and were not due to restriction of energy intake (Gómez et al 2007). These results indicate that restriction of protein intake is responsible for the well-known decreases in mitROS production and oxidative stress that take place in DR. On the other hand, although it is classically believed that the anti-aging effect of DR is due to the decreased intake of calories themselves rather than to decreases in specific dietary components, recent findings question this consensus (Mair et al 2005).…”

Regulation of Membrane Unsaturation as Antioxidant Adaptive Mechanism in Long-lived Animal Species

“…[71][72][73] Thus, a decrease in membrane unsaturation, lipid peroxidation and lipoxidation-derived damage has been reported in tissues (liver, heart, and brain) from these dietary restrictions in rats and mice. [74][75][76][77][78][79][80][81][82][83][84] CR has also been shown to reduce levels of lipofuscin in tissues of rodents and C. elegans. [62,[85][86][87][88] From these studies it can be inferred that the magnitude of the change is modest for membrane unsaturation (between 2.5-10%) than that for the lipoxidation-derived molecular damage (between 20-40%) likely due to the added effect of the lower mitochondrial free radical generation also induced by these nutritional interventions.…”

Hormetic Interventions in Aging

“…Beneficial effects of other CR regimens, such as chronic 25 and 8.5% CR [108] and intermittent CR (once or twice a week) have also been reported [109,110] However, the universal applicability of CR as an antiaging and lifespan extending intervention, especially in human beings, is a highly debated issue at present [111][112][113][114][115][116][117][118][119][120][121][122][123][124] . In any case, some beneficial and health promoting effects of CR have been reported even for human beings.…”

“…• Increase in nucleotide excision repair [136] • Increase in the level of chaperones [132,137,138] • Increase in the level of proteosomal activities [132,137,138] • Enhancement of lysosomal autophagy [139,140] • Reduction in mitochondrial free radical generation and increase in mitochondrial uncoupling [108,141,142] • A shift in the metabolic regulation involving sirtuins and insulin-dependent pathways [143][144][145][146] …”