Women’s and men’s organs age differently, and aging clocks should know it

A biological aging clock is a computer model that looks at measurements from your body, such as an MRI scan or the levels of thousands of proteins in your blood, and guesses your age. The interesting number is the gap between the guess and your real age. If your liver “looks” 58 at 50, the gap is +8 years, a sign that the liver may be aging fast. Researchers call this gap the biological age gap.

Women and men age differently: women live longer on average but often have more illness late in life, men get heart and metabolic disease earlier, and women make up a larger share of people with Alzheimer’s disease. Yet most clocks are trained on women and men together. A study in Nature Medicine asks what changes when you build the clocks separately.

What they did

The researchers built 38 clocks: 20 for women and 18 for men, covering 15 organ systems (such as brain, heart, liver, kidney, immune system, fat tissue) and three kinds of data: organ MRI scans, about 3,000 blood proteins, and blood metabolites. Each clock compares a person with healthy people of the same sex. They then asked three questions: are the clocks shaped by different genes, are they linked to different diseases, and do they predict death and dementia equally well in women and men?

What they found

Separate clocks worked at least as well. For fat tissue, where women and men differ a lot, the single-sex clock was more accurate and less prone to overfitting (learning quirks of the training data) than a mixed clock of the same size. Typical clocks were off by about five years on average, similar to earlier mixed models.

Different genes, different weak spots. The genetic analyses found that liver and metabolic aging seemed more strongly inherited in women, and immune-related aging more so in men. Using a genetic method that tries to tell cause from coincidence (Mendelian randomization), they found that many links between diseases and organ aging showed up in only one sex. For example, a genetic tendency to sleep disorders was linked to immune-metabolic aging in women only.

Different predictions. Over about two decades of hospital records, the clocks for women were linked to a small set of later diagnoses: for example, a faster-aging heart (on MRI) to high blood pressure, and faster metabolic aging to high cholesterol and type 2 diabetes. In men the pattern was broader and spread over more organs, including high cholesterol, diabetes, heart-rhythm problems and kidney disease. Older-looking organs were linked to a higher risk of death in both sexes, through a somewhat different set of organs in each.

Brain age and Alzheimer’s. In people with mild memory problems, an older-looking brain on MRI predicted progression to Alzheimer’s in both sexes, more strongly in women: one standard deviation of extra brain age went with a 74% higher risk in men and more than double the risk in women.

What to keep in mind

These are statistical patterns in large datasets, mostly from the UK Biobank, and the authors say they still need to be confirmed in another biobank of similar size; the genetic part included only people of European ancestry. The study treated sex as two categories and did not account for menopause or hormone therapy, which likely explain part of the differences (see our article on menopause and brain aging). The authors also stress that women and men share most of their aging biology, and that mixed clocks remain useful.

Why it matters

Aging clocks are being proposed as quick ways to test anti-aging treatments and to pick people for trials. If a clock measures everyone against a mixed “average” body, it may miss problems that matter in one sex. This study argues that the reference should match the person.