[Show abstract][Hide abstract] ABSTRACT: Mitochondria are the main source of free radical species and the most direct target for their damaging effects, which especially affect the brain mitochondrial function, which is better maintained by females than males. The aim of this work was to investigate the age-related changes in rat brain mitochondrial oxidative status focusing on sex differences. Male and female rat brain from four different age groups (6, 12, 18 and 24 months old) were analyzed. Oxidative damage accumulates in rat brain throughout aging, related to the increasing activity of mitochondrial respiratory chain (MRC) and failure of several antioxidant defenses. The aging effect was less marked in females, which accumulated less oxidative damage than males due in part to their greater antioxidant capacity, such as higher GPx activity and higher UCP5 level. This sexual dimorphism gradually increased during aging.
[Show abstract][Hide abstract] ABSTRACT: Aging is responsible for the decline in the function of mitochondria and their increase in size and number--adaptive mechanism to restore mitochondrial function. Estrogens increase mitochondrial function, especially in female rats. The aim of this study was to determine the age-related changes in rat brain mitochondrial function focusing on sex differences. Cellular and mitochondrial protein and DNA content, mitochondrial oxidative and phosphorylative function in male and female rat brain from four different age groups (6, 12, 18 and 24 months old) were analyzed. Mitochondria protein/DNA content decreased with aging shifting toward lesser mitochondrial functional capacity and the mitochondria number increased. A sex dimorphism was determined, with female rat brain showing mitochondria with greater functional capacity than males. These sex differences gradually increased during aging.
[Show abstract][Hide abstract] ABSTRACT: Females show lower incidences of several neurodegenerative diseases related to oxidative stress and mitochondrial dysfunction than males. In addition, female rats show more differentiated mitochondria than males in several tissues. The aim of this work was to investigate the existence of sex-dependent differences in brain mitochondrial bioenergetics and oxidative balance in aged rats. Results showed that aged female rat brain had a lower mitochondria content than aged male brain but with a greater differentiation degree given the higher mitochondrial protein content and mitochondrial complex activities in females. Female rat brain also showed a better oxidative balance than that of males, reflected by the fact that higher mitochondrial respiratory chain function is accompanied by a similar ROS production and greater antioxidant enzyme activities, which could be responsible for the lesser oxidative damage observed in proteins and lipids in this sex. Interestingly, levels of UCP4 and UCP5--proteins related to a decrease in ROS production--were also higher in females. In conclusion, aged female rat brain had more differentiated mitochondria than male brain and showed a better control of oxidative stress balance, which could be due, in part, to the neuroprotective effect of UCPs.
Free Radical Biology and Medicine 11/2008; 46(2):169-75. DOI:10.1016/j.freeradbiomed.2008.09.035 · 5.74 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Caloric restriction (CR) has been shown to prevent the age-associated loss of mitochondrial function and biogenesis in several tissues such as liver, heart, and skeletal muscle. However, little is known about the effects of CR on a tissue in which the mitochondria have no adenosine triphosphate (ATP)-producing purpose but show a high degree of uncoupling, namely brown adipose tissue (BAT). Hence, the aim of the present study was to analyze the effect of long-term CR on BAT mitochondrial function and biogenesis. BAT mitochondria obtained from 24-month-old male and female rats previously subjected to 40% CR for 12 months were compared with mitochondria from old (24 months) and young (6 months) ad libitum fed rats. Old restricted rats compared to old ad libitum fed ones showed a reduction in BAT size with respect to fat content and adipocyte number. Mitochondrial DNA content in BAT increased with age and even more so in restricted rats, indicating a summative effect of age and CR on mitochondrial proliferation. CR induced resistance to lose total and mitochondrial protein, COX activity, and uncoupling capacity with advancing age, in relation with a lower decrease of mitochondrial transcription factor A (TFAM). In summary, our results demonstrate CR prevents the age-associated decline in mitochondrial function in BAT, probably in relation with a lower impairment of mitochondrial biogenesis.
Rejuvenation Research 07/2008; 11(3):597-604. DOI:10.1089/rej.2007.0626 · 3.31 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In the present study, we have investigated whether differences between male and female rats described in response to 40% caloric restriction (CR) were influenced by circulating level variations of sex hormones and/or insulin and leptin. Body weights (BW), organ weights, and adipose depot weights (ADW) were also measured. The most affected tissues by CR were the fat depots. Metabolically active organs were the least affected, especially more in females than in males (male weight lost: 24.3% vs. female: 17.3%). Testosterone and estradiol circulating levels did not show changes by CR. Insulin levels were decreased by CR in both genders, but was more evident in female rats than males. Leptin serum levels were higher in male rats than in females, and CR caused a circulating leptin level reduction only in males. In conclusion, our results indicate that leptin and insulin could be one of the keys of the different hormonal control of energy homeostasis in response to CR between female and male rats. In this sense, leptin serum levels correlated statistically with BW and with individual ADW only in male rats, whereas insulin serum levels correlated statistically with BW and with any of the ADW studied only in females.
Hormone and Metabolic Research 02/2008; 40(1):38-43. DOI:10.1055/s-2007-1004525 · 2.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Metabolic features and oxidative stress have been extensively studied in cancer cells. However, comparative studies between cancer cell populations that coexist in human neoplastic tissue are not frequently available. The aim of the present study was to characterize markers of oxidative status and mitochondrial function in center vs. periphery of human fresh glioma samples; therefore, antioxidant systems, oxidative stress and mitochondrial parameters were assessed in gross total resections of gliomas. Mitochondrial protein and mitochondrial DNA content, enzymatic activities of mitochondrial oxidative and phosphorylative system, antioxidant mechanisms, mitochondrial H(2)O(2) production, oxygen consumption and cellular oxidative damage were measured in human gliomas. Concentric regions of human glioma tissue showed similar mitochondrial structural markers; conversely, the functionality of their isolated mitochondria was significantly different. In this way, the tumor periphery exhibited higher respiratory rate and fewer antioxidant systems than tumor center. Our results have expanded previous investigations, which report the presence of cell populations with different oxidative susceptibility in human brain tumor samples. This is, to our knowledge, the first study to investigate metabolic differences in concentric regions of gross total resections of glioma. Interestingly, the cancer cell population that exhibits an increased antioxidant capacity within the tumor mass might be responsible for tumor resistance to chemotherapy and radiotherapy.
[Show abstract][Hide abstract] ABSTRACT: Caloric restriction (CR) without malnutrition has been shown to increase maximal life span and delay the rate of aging in a wide range of species. It has been proposed that reduction in energy expenditure and oxidative damage may explain the life-extending effect of CR. Sex-related differences also have been shown to influence longevity and energy expenditure in many mammalian species. The aim of the present study was to determine the sex-related differences in rat liver mitochondrial machinery, bioenergetics, and oxidative balance in response to short-term CR. Mitochondria were isolated from 6-mo-old male and female Wistar rats fed ad libitum or subjected to 40% CR for 3 mo. Mitochondrial O(2) consumption, activities of the oxidative phosphorylation system (complexes I, III, IV, and V), antioxidative activities [MnSOD, glutathione peroxidase (GPx)], mitochondrial DNA and protein content, mitochondrial H(2)O(2) production, and markers of oxidative damage, as well as cytochrome C oxidase and mitochondrial transcription factor A levels, were measured. Female rats showed a higher oxidative capacity and GPx activity than males. This sexual dimorphism was not modified by CR. Restricted rats showed slightly increased oxygen consumption, complex III activity, and GPx antioxidant activity together with lower levels of oxidative damage. In conclusion, the sexual dimorphism in liver mitochondrial oxidative capacity was unaffected by CR, with females showing higher mitochondrial functionality and ROS protection than males.