Effect of time of restriction on the decrease in mitochondrial H₂O₂ production and oxidative DNA damage in the heart of food‐restricted rats

Abstract

In the present study, the question if medium-term (4 months) caloric restriction (40%) decreases mitochondrial H2O2 production and oxidative DNA damage was investigated. Caloric restriction (CR) is the only experimental manipulation that increases maximum life span. Previous long-term CR studies have showed that CR decreases the mitochondrial rate of free radical production in diverse tissues and species. Those studies agree with the idea that the superior longevity of the restricted animals can be partly due to their lower mitochondrial rate of free radical generation. However, caloric restriction effects strongly depend on implementation time. Previous studies have shown that the decrease induced by CR on oxygen radical generation and oxidative damage to mitochondrial DNA occurs after 1 year but not after 6 weeks of restriction. In the present investigation, mitochondrial H2O2 production did not change in medium-term (4 months) caloric restricted animals, and, in agreement with that, no differences were found in either mitochondrial or nuclear oxidative DNA damage between restricted and ad libitum-fed animals. These results confirm the importance of the time of CR implementation, and show that time longer than 4 months is needed to decrease the mitochondrial rate of free radical generation and the oxidative damage to mtDNA in the rat heart.

Long-term caloric restriction increases UCP3 content but decreases proton leak and reactive oxygen species production in rat skeletal muscle mitochondria

“…Interestingly, we also observed an age-related increase in the rate of H 2 O 2 production; it was 18% higher (P Ͻ 0.01) in the 24-mo-old control rats compared with the 18-mo-old control rats. These results are consistent with the oxidative stress theory of aging (65) and with previous studies in heart (40% CR for 1 yr) and gastrocnemius muscle (40% CR for 21 mo), which demonstrated decreased H 2 O 2 production (18,22). Studies in liver mitochondria have shown mixed results; long-term CR resulted in decreased H 2 O 2 production, whereas no difference in H 2 O 2 production was observed after short-or medium-term CR [40% CR for 1 or 6 mo (58)].…”

Skeletal Muscle of Female Rats Exhibit Higher Mitochondrial Mass and Oxidative-Phosphorylative Capacities Compared to Males

“…The differential centrifugation process for subsarcolemmal mitochondria isolation was modified from previous described [21]. Briefly, gastrocnemius muscles were homogenized with a Teflon/glass homogeniser in 25mL of isolation buffer (manitol 220mM, Sucrose 40mM, EDTA 1mM, Tris-HCl 10mM, pH 7.4) adding 25mg of bovine serum albumin free fatty acids.…”

p66Shc-generated Oxidative Signal Promotes Fat Accumulation

“…Treatment with antioxidants prevents in vitro differentiation of pre-adipocytes and, in mice, diet-induced obesity (14). Caloric restriction in laboratory rodents reduces their adipose tissue mass, extends lifespan, and is associated with decreased oxygen metabolism and, consequently, mitochondrial H 2 O 2 production (15,16). It is not clear, however, whether these effects of H 2 O 2 or antioxidants on fat development are mediated by modifications of the insulin/ IGF1 signaling pathway in the adipose tissue.…”