Human supercentenarians share at least one thing in common--over 95 percent are women. Scientists have long observed differences between the sexes when it comes to aging, but there is no clear explanation for why females live longer. In a discussion of what we know about stem cell behavior and sex, Stanford University researchers Ben Dulken and Anne Brunet argue that it's time to look at differences in regenerative decline between men and women. This line of research could open up new explanations for how the sex hormones estrogen and testosterone, or other factors, modify lifespan.

It's known that estrogen has direct effects on stem cell populations in female mice, from increasing the number of blood stem cells (which is very helpful during pregnancy) to enhancing the regenerative capacity of brain stem cells at the height of estrus. Whether these changes have a direct impact on lifespan is what's yet to be explored. Recent studies have already found that estrogen supplements increase the lifespan of male mice, and that human eunuchs live about 14 years longer than non-castrated males.

More work is also needed to understand how genetics impacts stem cell aging between the sexes. Scientists have seen that knocking out different genes in mice can add longevity benefits to one sex but not the other, and that males in twin studies have shorter telomeres--a sign of shorter cellular lifespan--compared to females.

"It is likely that sex plays a role in defining both lifespan and healthspan, and the effects of sex may not be identical for these two variables," the authors write. "As the search continues for ways to ameliorate the aging process and maintain the regenerative capacity of stem cells, let us not forget one of the most effective aging modifiers: sex."