X chromosome leads to age-related diseases in women

Why are women more likely to experience dementia, autoimmune diseases or deteriorating heart function as they age? Answers to this question have long been sought, citing hormones or lifestyle. Now, however, a new, much deeper biological mechanism has emerged that could explain the differences between men and women in the aging process and the onset of disease.

Researchers from the Technical University of Munich have found a curious pattern. With age in women begins to activate the second X-chromosome, which all life was silent, did not manifest itself. Usually one of the two X chromosomes in women ‘switches off’, turning into a dense and inactive structure known as Barr’s calf. This is to prevent cells from getting a double dose of the same genes.

But it turns out that over the years this silence is broken. Some parts of the ‘sleeping’ chromosome become active, especially in areas that used to be dense structures. In the kidneys, for example, in elderly mice, almost 9% of genes on the inactive X chromosome began to work again – this is three times more than in young individuals. On average, activity doubles in other organs.

And this is not just a molecular fluke. Among the ‘awakened’ genes are many that are associated with disease. One of them, ACE2, may protect against pulmonary fibrosis. In contrast, another, TLR8, is associated with autoimmune disorders such as systemic lupus erythematosus, which manifests more often in women in adulthood.

Until now, attempts to understand the differences in disease incidence between the sexes have more often centred on estrogen levels or environmental influences. But now it has become clear: in women’s cells with age begin to sound genes that for decades were ‘switched off’.

If these silent areas really affect health, it will open the way to the creation of new diagnostic methods and personalised approaches to the treatment of women in age. After all, if the cause lies in ‘awakened’ genes, it will be possible to interact with them directly.

Such a mechanism could also explain another mystery – why women live longer. Although it has yet to be proven, the activity of the X chromosome in the second half of life, perhaps, gives the body of women additional resources to combat age-related changes. The question is what price to pay for this – and whether the side effects can be avoided.