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It has long been known that women on the average outlive men by about 5.9 years, regardless of socioeconomic status or culture. This increase in female longevity is even observed in the animal kingdom. While several theories have been proposed to explain this female longevity advantage, there has yet to be a clear answer. Dr. Dena Dubal, associate professor of neurobiology at the University of San Francisco (UCSF), proposed that a plausible explanation as to why females have evolved to live longer lives is due to their natural drive to ensure the safety of their offspring. Since there is a lack of understanding and limited research surrounding women’s longevity, Dr. Dena Dubal and her team of researchers at UCSF decided to take a deeper dive to find a scientific explanation looking at differences in sex chromosomes and gonadal hormones.

“…a very plausible explanation as to why females have evolved to live longer lives is due to their natural drive to ensure the safety of their offspring.”

It is known that most biological women have two X chromosomes, while most biological men have one X and one Y chromosome. The X chromosome is genetically stronger than the Y chromosome since it contains hundreds of protein-encoding genes, and the Y chromosome carries the SRY gene which is responsible for the development of testes among other male traits. Could the double X chromosome found in the genetic makeup of biological women be responsible for their advantage in longevity? While this could be a potential component contributing to their extended lifespan, it may not end there. The researchers also aimed to develop a further understanding of the effect that the sex hormones secreted in either the ovaries or the testes have depending on the genetic material. Their results confirmed their hypothesis that both genetics and hormones play a significant role in the difference between the lifespan of men and women.

Could the double X chromosome found in the genetic makeup of biological women be responsible for their advantage in longevity?

The study performed by UCSF scientists consisted of modifying both the genetic material and hormonal profiles of mice to better understand how these two factors affect longevity. They used a total of four groups of genetically engineered mice to determine how their chromosomal pairings correlated with their hormone levels and longevity. In the first two groups, the mice had the genetic material corresponding with the hormonal profile that would most likely naturally occur. The researchers kept the genetics and hormonal profile consistent of these mice by using one group with both X chromosomes and ovaries, and the second group having an XY chromosome and testes. For the third and fourth group, they used mice with the chromosomal pairings and hormonal profiles that were not commonly occurring in nature. The mice in the third group had XX chromosomes and hormones that were secreted in the testes, and the fourth group of mice with XY chromosomes and hormones that were secreted in the ovaries. They were able to achieve the groups of genetically engineered mice by moving the SRY gene to a different chromosome that would not be responsible for determining the sex. The four groups provided researchers a variety of combinations that enabled them to understand how genetics and hormones both have a significant influence on the intrinsic lifespan of female animals.

“The researchers used a total of four groups of genetically engineered mice to determine how their chromosomal pairings correlated with their hormones would be a determining factor of their lifespan.”

The results of this study indicated that XX chromosomal pairing contains the genetic makeup that is responsible for extended lifespan, but only when female hormones secreted in the ovaries are also present. However, the researchers also found that regardless of hormones, the mice with two X chromosomes still tended to outlive the mice with XY chromosomes. On the other hand, the mice with two X chromosomes and an absence of female hormones, did not show an effect on longevity. The hormones produced in the ovaries were found to be responsible for increasing lifespan in the mice who also had XX chromosomal pairings. This is thought to either be attributed to how the mice develop or by specific biological pathways being activated.

The science as to why the second X chromosome decreases risk of early mortality is still unclear and future research is needed to explain the reasoning behind this. Research is limited, but scientists still hypothesize that this could be due to the inactive X chromosome having the possible ability to step in for the active X chromosome in the circumstance that it would be damaged. Perhaps it is even possible that the extra X chromosome is not necessarily beneficial, but that the SRY gene carried by the Y chromosome actually proposes a risk of early mortality. Regardless of the reason, it is still apparent that those who have X chromosomal pairings seem to be quite fortunate when aging considering the ability that they have to outlive those with an XY chromosome.

“It appears that those who have X chromosomal pairings seem to be quite fortunate when aging considering the ability that they have to outlive those with an XY chromosome.”

The findings indicated that the XX chromosome mice will outlive the XY chromosome mice, but it is important to note that they still need the female hormones secreted in the ovaries to be considered to have an increased lifespan. On the other hand, not all the mice with the XY chromosomes were able to live a normal lifespan and some had died in their early age. With this being said, the odds of living a longer life are still in favor of those with two X chromosomes regardless of their hormonal profile.

Future research is needed to explain the role that the inactive X chromosome plays in aging, or the reason as to why it is beneficial to have both X chromosomes. For the time being, the findings of this research can provide an in-depth explanation into the intrinsic cause of female longevity.