A protein responsible for protecting genes and keeping gene activity in check could be playing a role in why a male and female body responds differently to disease or ageing, research suggests.

Researchers from Mass General Brigham, a US-based integrated healthcare system, and Spain's Josep Carreras Leukaemia Institute said that biological reasons for sex-based differences in how a disease develops or how the body ages are not fully understood.

Sex chromosomes are being looked at by scientists to better understand what might be driving the differences.

Findings published in the journal Nature show that 'SIRT7', a protein involved in how cells respond to stress and ageing, plays a critical role in maintaining the health of the X chromosome, one of two sex chromosomes that determine one's biological sex.

Females typically carry two X chromosomes (XX) while males carry one X and Y chromosome (XY).

In female cells, one of the X chromosomes is normally 'turned off' to keep gene activity balanced.

The researchers conducted experiments in mice and found that when SIRT7 is missing, the balance breaks down -- the inactive X chromosome became overly silenced and the active one too active.

The overactivity disrupts normal gene regulation and makes the active X chromosome prone to damage DNA and genome instability, they said.

The effects were found to be strongest among females, as female animal models lacking SIRT7 showed more DNA damage, poorer health, and shorter lifespans compared to males.

"(An) increased (active X chromosome) expression leads to genome imbalance and (an) augmented X-chromosome upregulation," the authors wrote.

SIRT7 could thus be safeguarding X-chromosome integrity, keeping the active X chromosome stable and its gene activity balanced, they said.

The team said the research provides a new insight into why ageing, disease risk, and biological responses can differ between sexes.

By uncovering how the X chromosome is regulated, the study may help inform future approaches to treating conditions that affect females and males differently, they said.

"We propose that the sex bias in SIRT7 biology can be explained in part by unequal effects on the sex chromosomes," the authors wrote.

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