The X and Y chromosomes may be best known for their role in determining biological sex, but scientists are finding that their influence reaches much further. A new review published in Science suggests these chromosomes can shape how our bodies age, fight disease and respond to treatment throughout our lives.

For decades, many health differences between men and women have been explained largely by hormones such as estrogen and testosterone. But researchers say that is only part of the story. Genes carried on the X and Y chromosomes can have their own effects on the body, influencing everything from the immune system and metabolism to cancer, heart disease and brain ageing.

The review was co-led by University of Arizona Cancer Center physician-scientist Dr. Dan Theodorescu and Dr. Dena B. Dubal of the University of California, San Francisco. Drawing on evidence from human studies, mouse research and genomic technologies, the scientists examined how sex chromosomes may affect disease risk, progression and responses to treatment.

“X and Y chromosomes are often thought of as simple determinants for biological sex, but their role in human health is much larger,” Theodorescu said. According to the researchers, the chromosomes carry genetic instructions that can influence how cells age and how the body protects itself against major diseases.

The X chromosome offers a particularly intriguing example. Women generally have two X chromosomes, but one is largely switched off early in development. That shutdown is not always complete. Some genes remain active, while others may switch back on as people age, potentially giving female cells extra doses of certain genes. Animal studies also suggest that whether an active X chromosome comes from the mother or father could affect brain ageing and memory.

Age can bring other changes. Some cells may lose a sex chromosome altogether. In women, loss of an X chromosome has been associated with a higher risk of leukaemia. In men, loss of the Y chromosome in blood cells has been linked to cancer, heart disease, severe infections and Alzheimer’s disease. Scientists are now studying whether these changes signal ageing and disease or actually help drive them.

Cancer research is already providing important clues. Theodorescu’s laboratory has found that tumours that lose the Y chromosome can become better at escaping attack by the immune system. Surprisingly, those tumours may also respond better to immunotherapy. His team’s other research suggests Y chromosome loss in seemingly normal tissue could potentially serve as an early warning sign of genetic changes associated with cancer.

The findings could eventually change how researchers think about disease prevention and treatment. Paying closer attention to the X and Y chromosomes — rather than focusing primarily on hormones — could help explain why diseases develop differently from one person to another and why the same treatment does not always produce the same results. The researchers say designing clinical trials with these biological differences in mind could ultimately lead to more precise diagnoses and treatments tailored to individual patients.

More information: Dena B. Dubal et al, X and Y chromosomes as determinants of aging and disease, Science. DOI: 10.1126/science.aeh0145

Journal information: Science Provided by University of Arizona