Sex and stem cells – sexual dimorphism of longevity
A new study in Cell Stem Cell, discusses sex and stem cells or the ‘sexual dimorphism of longevity’, wherein most of supercentenarians are female, linking this to increased stem cell self-renewal and regeneration potential in females.
Of note, in the list of the oldest living people (as of 18 August, 2022), or supercentenarians – out of the 50 oldest living people – only 5 are male. In fact, human supercentenarians share at least one thing in common – over 95 percent are women.
With the passing of Japan’s Kane Tanaka at the age of 119, the title of ‘oldest living human’ has been bequeathed to the French born Lucile Randon. At the ripe old age of 118, she sits atop the infographic below.
According to the 2005 U.S. Social Security Administration’s birth cohort life tables, for example, out of 100,000 people born in 1910, 3,795 were estimated to survive to 100 years old and older of which 14% were men and 86% were women. The difference becomes even more pronounced for males and females surviving to age 105+ years, who for the 1910 birth cohort, for example, are comprised of 10% men and 90% women.
Yet, sexual dimorphism with respect to longevity is a characteristic of most mammals. This raises questions regarding the mechanisms driving the sexual dimorphism of longevity.
Scientists have long observed differences between the sexes when it comes to aging, but there is no clear explanation for why females live longer. Interestingly, as they approach the limit of lifespan, that is, supercentenarians, the men and women are phenotypically much more alike, in that the majority of them are “escapers” and on average they delay both disability and mortality-associated age-related diseases until an average age of 106 years.
Stanford University researchers Ben Dulken and Anne Brunet argue that it’s time to look at differences in regenerative decline between men and women.
In the in Cell Stem Cell article Ben Dulken and Anne Brunet from the Stanford University Medical Scientist Training Program relate this phenomenon to increased stem cell self-renewal and tissue regeneration in female organisms.
It is known that most adult stem cell populations undergo an age-related decline, leading to dysfunctional tissue homeostasis.
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.
Mentioned are several studies aiming to elucidate the mechanisms responsible for the sexual differences in lifespan and health, including the differential utilization of steroid hormones, estrogen and testosterone that have been proposed to contribute to lifespan.
Estrogen appears to play a major role, but signaling pathways that do not involve estrogen are also involved – interestingly, male eunuchs (castrated males) have been noted to live as much as 14 years longer than non-castrated males.
Of note, estrogen increases the proliferation of neural stem cells (NSCs) in a transient manner that fluctuates throughout the estrus cycle – NSC proliferation is highest during the proestrus phase of the estrus cycle, when estrogen levels are particularly high.
According to the authors, many questions remain unanswered regarding the effects of sex on stem cells, although the importance of sex as a variable in longevity is now well-established. This includes the fact that adult stem cells in non-sexual tissues are regulated in a sexually dimorphic manner and are responsive to the effects of sex hormones.
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