It is common knowledge that American and most European women, on average,live longer than men, possibly because women take better care of their health overall and are more likely to see a doctor! But females of other species also live longer, including rats, other primates, and ungulates, suggesting a sex-specific mechanism that increases lifespan. It has been proposed that estrogens might be protective by decreasing the damage caused by reactive oxygen species (ROS) by increasing antioxidant defenses, thus reducing the chance of cellular senescence and death. But in some animals there is no sex-linked difference in longevity despite higher female estrogen levels, and in other species, such as Syrian hamsters, males live longer. Thus, Alberto Sanz from Complutense University, Madrid and collaborators at the University of Florida and University of Wisconsin analyzed a number of parameters of oxidative stress in a strain of mice with no male-female differences in longevity to determine if there were sex-linked differences in oxidative stress.

The team used 10-month-old male and female mice to determine mitochondrial oxygen consumption, ATP content and production of the ROS hydrogen peroxide in liver, skeletal muscle and heart tissue when they inhibited aerobic respiration. These measures would reveal any gender differences in basal metabolism or ROS production. They also measured oxidative damage to mitochondrial DNA (mtDNA) and levels of protein carbonyls that result from oxidative protein damage. To calculate the amount of apoptosis - programmed cell death - in male and female tissues they measured the levels of caspase-3 and caspase-9 enzymes, which break down proteins during apoptosis, and levels of DNA fragmentation that could indicate sex-specific differences in cellular damage.

The group found no significant differences between males and females for nearly every parameter measured, including oxygen consumption, ATP content and ROS production. There were also no differences in oxidative stress markers -cytosolic protein carbonyls or mtDNA damage - nor were there sex differences in apoptotic markers. Since the female mice had twice the levels of estrogen compared with the male mice, this means that high estrogen levels alone do not reduce ROS production, at least in this strain of mice.

The only real differences between the sexes was body mass: males weighed on average 20% more than females. Since male and female mice had similar lifespans and no differences in ROS production or oxidative damage, the group's results agree with several studies in rats that have demonstrated reduced ROS production in longer-living animals. The authors suggest that levels of ROS production may be linked to body mass differences between genders, as the size difference is much smaller in mice at 11-20% than in rats at 70%, and in general there is a negative correlation between body mass and longevity within species. Small animals also have a higher mass-specific oxygen consumption, and other researchers have found that increases in mitochondrial oxygen consumption decrease ROS production. Thus, large male rats would have higher rates of ROS production and ROS damage than female rats, while mice without gender-related size differences would have similar rates of ROS production and equal lifespans.

And so we learn that size does matter, and bigger isn't necessarily better!

Sanz, A., Hiona, A., Kujoth, G. C., Seo, A. Y., Hofer, T.,Kouwenhoven, E., Kalani, R., Prolla, T. A., Barja, G. and Leeuwenburgh, C.(
). Evaluation of sex differences on mitochondrial bioenergetics and apoptosis in mice.
Exp. Geront.