While the mechanisms of cellular aging remain controversial, a leading hypothesis is that mitochondrial oxidative stress and mitochondrial dysfunction play a critical role in this process. Here, we provide data in aging rhesus macaques supporting the hypothesis that increased oxidative stress is a major characteristic of aging and may be responsible for the age-associated increase in mitochondrial dysfunction. We measured mitochondrial DNA (mtDNA) damage by quantitative PCR in liver and peripheral blood mononuclear cells of young, middle age, and old monkeys and show that older monkeys have increases in the number of mtDNA lesions. There was a direct correlation between the amount of mtDNA lesions and age, supporting the role of mtDNA damage in the process of aging. Liver from older monkeys showed significant increases in lipid peroxidation, protein carbonylations and reduced antioxidant enzyme activity. Similarly, peripheral blood mononuclear cells from the middle age group showed increased levels in carbonylated proteins, indicative of high levels of oxidative stress. Together, these results suggest that the aging process is associated with defective mitochondria, where increased production of reactive oxygen species results in extensive damage at the mtDNA and protein levels. This study provides valuable data based on the rhesus macaque model further validating age-related mitochondrial functional decline with increasing age and suggesting that mtDNA damage might be a good biomarker of aging.

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Correlative evidence from comparative studies has suggested that longevity in higher eucaryotes keeps an inverse correlation with the unsaturation degree of mitochondrial membranes. Since lipid peroxidation (LP) depends on the number of double bonds, it has been hypothesized that lower unsaturation degree of the membranes from longevous animals preserves mitochondrial function from the damage by ROS. To further test this hypothesis, we have studied if accelerated aging and impaired mitochondrial function by the incorporation of PUFA in the yeast is associated with increased sensitivity to LP and enhanced ROS production. When yeast incorporated C18:3 into mitochondrial membranes, it was observed accelerated aging along with increased ROS production, which was attributed to impairment in electron transfer between complex II and complex III. These effects were associated with a higher susceptibility to LP, although the cells become more resistant to this process at late stages of aging. These data confirm the observations made in higher eukaryotes about the primordial role of LP in the mitochondrial impairment associated to a lower longevity. This work was funded by a CONACYT (130638 to CCR) grant.

Ca2+ participates as a second messenger in a myriad of metabolic and physiologic processes in the brain, with mitochondria controlling Ca2+ transients through its uptake and release. Hypertension (HT) is known to impair mitochondrial Ca2+ homeostasis in association with respiratory chain dysfunction. As many of the deleterious effects of HT are related with increased oxidative stress, the goal of this study was to assess whether avocado oil, an important source of antioxidants, prevent the deleterious effects of HT in brain mitochondrial calcium handling and mitochondrial function and to compare its effects with losartan, an antihypertensive drug. Ca2+ uptake and release was decreased in L‐NAME‐induced HT rats and this effect was fully prevented by losartan, with avocado oil dietary intake exhibiting a slight protective effect. In mitochondria from control rats, respiration was negatively modulated by 40µM Ca2+ and this effect was absent in mitochondria from hypertensive rats. Modulation of respiration by Ca2+ was recovered either by losartan or avocado oil. These results suggest that losartan improves the modulatory effects of Ca2+ in mitochondrial function by preventing the impairment in mitochondrial Ca2+ handling, while avocado oil exert the same effect of losartan on the modulation of mitochondrial function without having an apparent effect on Ca2+ handling. Supported by CONACYT (130638 to CCR) and CIC‐UMSNH (CCR) grants