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A review published in Science brings together human, animal and genomic research on how X and Y chromosome genes may influence immunity, aging, cancer and other health conditions. The authors say these effects can work alongside sex hormones, but many mechanisms and clinical uses remain under investigation.
A review published in Science synthesizes research suggesting that genes on the X and Y chromosomes influence immunity, cancer, aging and other disease risks, in addition to the effects of sex hormones. The review’s authors say the findings could inform research on diagnosis, treatment and clinical-trial design, although many proposed links still need further study.
The review was co-led by Dan Theodorescu, a physician-scientist at the University of Arizona Cancer Center, and Dena B. Dubal of the University of California, San Francisco. It evaluates findings from human studies, mouse models and genomic technologies on how sex chromosomes affect cell function over a person’s lifespan. Its scope includes immune function, metabolism, brain aging, cancer, neurological conditions and cardiometabolic disease.
The authors argue that differences in disease risk and treatment response cannot be explained by circulating estrogen or testosterone alone. Genes on the sex chromosomes can act directly and in combination with hormones. In women, one X chromosome is largely inactivated early in development, but some genes escape that process; some may also become active again with age. This can leave cells with different doses of certain X-linked genes.
The review also describes changes in chromosome number as people age. Loss of an X chromosome in women is associated with increased leukemia risk, while the broader health effects are less established. In men, loss of the Y chromosome—often detected in blood—has been associated with cancers, heart disease, severe infections and Alzheimer’s disease. The review presents chromosome loss as an area being investigated as both a possible disease marker and a potential contributor, not as proof of causation.
How Chromosome Biology Could Shape Care
The review matters because it brings sex chromosomes into a discussion of health differences often framed mainly around hormones. If chromosome-linked effects are confirmed and shown to matter clinically, they could help explain why people with similar diagnoses respond differently to disease or treatment. The authors say this biology may have implications for risk assessment, diagnostics and treatment selection.
One example is cancer. Theodorescu said his laboratory’s research found that tumors that lose the Y chromosome can evade immune defenses, while potentially responding better to immunotherapy. Those findings point to a possible connection between tumor chromosome status and treatment response. They do not establish that Y-chromosome loss predicts benefit for an individual patient, and the review calls for more investigation before such insights can guide routine care.
The authors also connect the work to the design of clinical trials. Accounting for sex and chromosome-related biology could help researchers test whether a treatment works differently across groups, rather than assuming results apply uniformly. That is a research goal raised by the review, not evidence that current clinical practice has already changed.
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From Hormones to Chromosome Effects
Sex differences in health have often been discussed through the effects of hormones such as estrogen and testosterone. The review adds evidence about the chromosomes that help determine biological sex, emphasizing that their genes remain active participants in cell processes. The authors’ argument is not that hormones are irrelevant, but that chromosomal and hormonal influences can operate together.
The review grew out of discussions at the 2025 National Institute on Aging workshop on sex differences affecting human health across the lifespan, including discussions with Francesca Duncan of Northwestern University’s Feinberg School of Medicine. It was authored by researchers including Fabrisia Ambrosio of Harvard Medical School’s Schoen Adams Research Institute and Michael B. Stout of the Oklahoma Medical Research Foundation. The paper is titled “X and Y chromosomes as determinants of aging and disease” and was published in 2026.
Earlier work from Theodorescu’s group examined Y-chromosome loss in men’s T cells and cancer cells, reporting that it could help tumors evade immune surveillance. Other research from the group described Y loss in normal-appearing tissue as a possible early warning sign of a hidden area of genetic risk. Those studies provide background for the review, but the new paper itself is a synthesis of existing evidence rather than a clinical trial.
““Our review shows that these chromosomes carry genetic instructions that shape how our cells age and how our bodies defend against major diseases throughout our lives.””
— Dan Theodorescu, co-lead author
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Evidence and Clinical Questions Remain
The review gathers evidence from several types of research, but it does not resolve how much each chromosome-linked mechanism contributes to a given person’s disease risk. Associations between chromosome loss and conditions such as cancer, heart disease or Alzheimer’s disease do not by themselves show that chromosome loss caused those conditions. The review says the effects of X-chromosome loss beyond its association with leukemia are still largely unknown.
Some findings come from mouse models and cannot automatically be applied to people. For example, research in mice has linked which parent’s X chromosome is active in cells with brain aging and memory decline; the relevance and extent of that effect in humans remain uncertain. It is also unclear how chromosome status might be measured and interpreted consistently, or which patients could benefit from testing.
The article reports no new clinical-trial results, approved diagnostic test or change to treatment guidance. The possible relationship between Y loss in tumors and immunotherapy response requires further validation before it can be used to make individual care decisions.
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Research Needed Before Clinical Use
The authors call for additional research into how X and Y chromosome genes affect disease and how those effects interact with hormones, age and other biological factors. Studies in people will be needed to test whether observations from laboratory research and animal models hold across populations and predict health outcomes reliably.
Future work will also need to establish whether chromosome changes can serve as useful biomarkers, whether they contribute directly to disease, or both. For cancer, researchers would need to test how reliably tumor Y-chromosome loss relates to immune evasion and response to immunotherapy. The review’s broader aim is to support sex-aware research and clinical trials; it does not set a timeline for changes to care.
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Key Questions
What is the new development?
A 2026 Science review synthesizes research on how X and Y chromosome genes may influence immunity, aging, cancer and other diseases, alongside the effects of hormones.Does the review show that hormones do not affect disease?
No. The authors say chromosome genes can act on their own and alongside hormones; the review adds chromosome biology to explanations that have often focused mainly on hormones.What does loss of the Y chromosome mean for health?
Y-chromosome loss, often measured in men’s blood, has been associated with several conditions, including cancer and heart disease. The review does not establish that the loss causes those diseases or that testing should guide care.Could the findings change cancer treatment?
The authors discuss research linking Y loss in tumors with immune evasion and a possible response to immunotherapy. More evidence is needed; the review does not announce a new treatment recommendation.What remains unknown?
Researchers still need to determine how strong these effects are in people, which findings are causal, and whether chromosome information can improve diagnosis or treatment decisions.Source: rss
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