After 30 years, scientists have proven that the second X chromosome in females provides them with more protection from age-related disorders, findings which could help in further studies about ageing and age-related diseases.

The research team, headed by Pau Carazo of the Department of Zoology at the University of Oxford, has shown that the second X chromosome contributes to the longer average lifespan of females compared to males.

These, published in Biology Letters, proves the decades-old unguarded X hypothesis.

Physiologically, the differences between males and females are both vast and universal; in nature, it’s almost everywhere. Specifically, men and women age differently and have different life expectancies. In general, women have longer life spans than men.

Several hypotheses attempt to explain this, but there are three that are currently most widely accepted. The first focuses on extrinsic factors – the difference in social, environmental, and sexual pressures have resulted in a differential selective and evolutionary pressure in favour of females.

The second hypothesis, often called the mother’s curse hypothesis, relies on the fact that mitochondrial DNA (mtDNA; our only extra-chromosomal DNA) is only passed down from mothers. Therefore, according to the hypothesis, mutations in the mtDNA that affect only males, cannot be removed through natural selection.

Finally, the final theory proposes that, because females have two copies of the X chromosome, both from different parents, they have two copies of the genes on this chromosome.

Thus, when one copy is mutated, the other can take over its function, somehow acting as a reserve or a buffer. And, since males do not have this luxury, this is called the unguarded X hypothesis.

Most probably, the real reason involves a combination of these three hypotheses, and perhaps even more factors. However, the team decided to focus on the unguarded X hypothesis which, thus far, has had no substantial empirical evidence to support or refute it.

In their experiments, they used fruit flies which are suitable animal models to use for genetic studies. Their study was based on the assumption that, because their longer lifespan is due to a protected X chromosome, females will be more affected by inbreeding (which makes both X chromosomes identical to each other) than males.

Males, because they have the unguarded X, should experience no change in their lifespans due to inbreeding. Basically, through inbreeding, the team tried to unguard the guarded X chromosome in female fruit flies.

The research team discovered that, indeed, outbred females outlived both outbred males and inbred females. In fact, inbreeding reduced the lifespan for both males and females, but the effect was much more pronounced in females.

Remarkably, the lifespan of both inbred males and females were statistically identical.

These findings represent one of the first few solid empirical pieces of evidence supporting the unguarded X hypothesis. Thus, they have shown that differences in the genes that the two sexes inherit have a profound impact on the lifespan of the individuals. MIMS