For years, aging medicine treated the immune system as one system that deteriorates at a similar rate in everyone. A groundbreaking new study published in Nature Aging debunks this assumption. The team, led by Prof. Marta Mele from the Broad Institute and her colleagues, analyzed 982 blood samples from men and women of all ages, and discovered: Women's immune systems age dramatically differently, and in general, faster.
How was the research done?
The researchers used a technology called "single-cell RNA sequencing", in which the genetic expression of each cell is analyzed separately. This way they identified specific immune cell populations and the changes they underwent in each age group. Comparing women against men at any age revealed distinct sex-specific patterns.
What happens in women?
The team identified three key changes that are more specific to women:
- Expansion of CD8+ Effector Memory T cells. These cells are the "destroyers" of the immune system, whose job it is to kill infected cells. Their expansion in old age may explain the symptoms of chronic inflammation in older women
- Expansion of inflammatory monocytes. Monocytes are blood cells that specialize in an inflammatory response. Overexpression in older women is directly linked to heart disease and diabetes
- Changes in CD4+ Central Memory cells. These are the memory cells that are responsible for a rapid immune response to known pathogens. The changes identified in the study were found in genetic loci that are linked to autoimmune diseases such as lupus, RA, and MS, diseases that are 4-9 times more common in women
What happens in men?
In some of the men, the team identified another phenomenon: the expansion of a certain B-cell population that is linked to Chronic Lymphocytic Leukemia (CLL), a type of blood cancer. Specifically, a pattern was identified that appears in a pre-symptomatic state, that is, even before a disease manifests itself clinically.
This finding is dramatic: it is possible that in the future we will be able to test the blood of men aged 50-60 and identify who is at increased risk of CLL years before the diagnosis.
Why is this happening?
Not all factors are known, but the team suggests some mechanisms:
- Hormones. Estrogen has a strong modulatory effect on the immune system. A drastic drop in estrogen during menopause changes the whole system
- Genetics of the X chromosome. The X chromosome contains several key immune genes. Women, with two copies, get an "extra" which can be protection but also hypersensitivity
- Pregnancy and childbirth. Every pregnancy takes advantage of the immune system. Cumulative effects throughout life
Why does it matter to treatments?
The researchers conclude that it is time to move from "uniform medicine" to "sex-specific medicine":
- Vaccines. Women may need different vaccination protocols, especially after menopause
- Anti-inflammatory supplements. Antioxidant supplements, omega-3, and curcumin may be more effective in women
- hormone replacement therapy (HRT). The relationship between HRT and immune inflammation in menopause gets a new explanation
- Screening of men for CLL. Men over 50 who have a family history of blood cancer may benefit from routine screening
The bottom line
"Personal health" is not just about diet and exercise. It's also about understanding that your body, at certain points in your life, behaves differently than someone else's body. This research is a big step towards truly personalized medicine, within a body that changes throughout life.
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