Evaluation of sex differences on mitochondrial bioenergetics and apoptosis in mice

Abstract

SummaryIt has been postulated that the differences in longevity observed between organisms of different sexes within a species can be attributed to differences in oxidative stress. It is generally accepted that differences are due to the higher female estrogen levels. However, in some species males live the same or longer despite their lower estrogen values. Therefore, in the present study, we analyze key parameters of mitochondrial bioenergetics, oxidative stress and apoptosis in the B6 (C57Bl/6J) mouse strain. There are no differences between males and females in this mouse strain, although estrogen levels are higher in females. We did not find any differences in heart, skeletal muscle and liver mitochondrial oxygen consumption (State 3 and State 4) and ATP content between male and female mice. Moreover, mitochondrial H 2 O 2 generation and oxidative stress levels determined by cytosolic protein carbonyls and concentration of 8-hydroxy-2′-deoxyguanosine in mitochondrial DNA were similar in both sexes. In addition, markers of apoptosis (caspase-3, caspase-9 and mono-and oligonucleosomes: the apoptosis index) were not different between male and female mice. These data show that there are no differences in mitochondrial bioenergetics, oxidative stress and apoptosis due to gender in this mouse strain according with the lack of differences in longevity. These results support the Mitochondrial Free Radical Theory of Ageing, and indicate that oxidative stress generation independent of estrogen levels determines ageing rate.

The role of estrogen deficiency in skin ageing and wound healing

“…Conversely, expression of 16S ribosomal RNA, a biological marker of youth (Calleja et al 1993), is substantially higher in female rats than males (Borras et al 2003;Vina et al 2005). Although, Sanz et al (2007) report no difference in oxidative stress, age-related damage or lifespan between male and female C57Bl6 mice, Ali et al (2006) show that females, the reported shorter lived gender, exhibit enhanced reactive oxygen species (ROS) production with age. Estrogen deficiency post-menopause is also strongly linked to altered oxidative state, with estrogen a potent direct antioxidant and indirect inducer of antioxidant enzymes.…”

“…Finally, it should be noted that while gender-specific effects are common across many species, including man (Gurwitz 2005), marsupials (Humphries and Stevens 2001) and non-human primates (Herndon et al 1999) this is not the case in all animal species. Some species lack gender difference in lifespan (Sanz et al 2007;Wich et al 2004) while in a limited number of species males actually live longer (Asdell and Joshi 1976;McCulloch and Gems 2003).…”

Sex Differences in Longevity and in Responses to Anti-Aging Interventions: A Mini-Review

“…The literature on aging is beset with confusion as to the existence or nature of sex differences in survival in mice [21] . One can find claims that males are the longer-lived sex [22] , that there is no sex difference [23] , and that females live longer [24] . It turns out that all of these authors are correct.…”

Gender difference as regards myocardial protein oxidation in aged rats: male rats have increased oxidative protein damage

“…Data from a few studies have suggested that there may be a link between gender, ageing, and differences in free radical homeostasis (Sameh et al 2006;Sanz et al 2007) Age-dependent alterations in redox signalling processes not clearly delineated, understood, or appreciated. Disruption of redox regulation likely contributes to the exponential agerelated rise in the level of oxidized protein, occurrence of disease, and precipitation of death (Humphries et al 2006).…”