Gene-protecting protein could be important for differences in male, female biology, study suggests

NEW DELHI, Jun 18: 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 the two sex chromosomes that determine biological sex.

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

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

The researchers conducted experiments in mice and found that when SIRT7 is absent, that balance breaks down. The inactive X chromosome becomes overly silenced, while the active X chromosome becomes excessively active.

According to the researchers, this overactivity disrupts normal gene regulation and makes the active X chromosome more vulnerable to DNA damage and genome instability.

The effects were found to be strongest in females. Female animal models lacking SIRT7 showed greater DNA damage, poorer health and shorter lifespans compared with males.

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

The researchers said SIRT7 appears to safeguard X chromosome integrity by keeping the active X chromosome stable and maintaining balanced gene activity.

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

By uncovering how the X chromosome is regulated, the study could 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. (PTI)