Rocío Guevara

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.

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.

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.