To reach this conclusion, researchers from Duke-NUS Medical School, Singapore, analyzed the genetic activity of
3.8 million immune cells from nearly 2,000 adults aged 19 to 97. Published in Nature Communicationstheir results draw a new map of the aging of our natural defenses.
At 40, our immunity changes pace
Immune aging would therefore not be a long, perfectly regular decline. The researchers identified two periods of particularly rapid change: around age 40 and after age 60.
They studied several families of immune cells present in the blood: T and B lymphocytes, NK cells and monocytes. Their attention was focused in particular on the genes necessary for the production of RNA and proteins, essential for the proper functioning of cells.
However, the activity of this cellular machinery decreases particularly during the two periods identified. T lymphocytes appear to be the main players in these transformations.
- Around the age of 40, CD4 T cells are particularly concerned;
- After 60 years, it is more CD8 T cells who take over.
This result is important because T lymphocytes play a central role in our defense against infections. With age, their transformations could help explain why the body becomes more vulnerable to certain infections and inflammatory phenomena.
“Our results build on previous data showing that T cells are among the immune cells most affected by aging. Understanding the mechanisms behind these nonlinear changes within T cells over time will be an important next step. Changes in T cell function may help explain why older people are more vulnerable to infections and inflammatory diseases.explains Associate Professor Jacques Behmoaras, lead author of the study, in the Duke-NUS Medical School press release.
In other words, these are not two ages at which immunity collapsesbut of two periods where certain biological transformations seem to accelerate.
Women, men: immunity does not age at the same rate
The study’s other finding is perhaps even more intriguing. Immune aging trajectories differ by sex.
Researchers have identified numerous molecular signatures specific to women. The first peak, around age 40, appears particularly more marked among them. After age 60, certain CD8 T lymphocyte activation programs also continue to evolve in women while they tend to stabilize more in men.
This difference could shed additional light on a well-known paradox: women generally live longer, but are more affected by certain autoimmune diseasessuch as lupus or rheumatoid arthritis.
“We tend to think of aging as a gradual process, but our results show that the immune system does not simply decline at a constant rate. Rather, we observe distinct periods of rapid change, notably around age 40 and after age 60, where T cells play a major role. Understanding the mechanisms behind these phases of immune aging could ultimately help us identify when and for whom interventions would be most beneficial. It could also explain why some autoimmune diseases disproportionately affect women.”explains Associate Professor Jacques Behmoaras, lead author of the study and member of the Center for Biomedical Data Science at Duke-NUS Medical School.
Scientists also observed differences in DNA methylation, notably in a region of chromosome 6 involved in the major histocompatibility complex (MHC). This region plays a critical role in how the immune system recognizes antigens. These results alone cannot yet explain why certain autoimmune diseases are more common in women. But they provide new biological leads.
What if immune aging could be better anticipated?
This is where this discovery could ultimately change the way medicine views aging.
“This study offers us a more precise vision of the evolution of the human immune system throughout life and, above all, of the differences between men and women. This knowledge is fundamental if we are to move away from a one-size-fits-all approach to aging and adopt more targeted methods to preserve the health of older people.”explains Professor Sheemei Lok, from Duke-NUS Medical School.
Researchers have already used their data to develop artificial intelligence models capable of estimating
biological age of the organism, which may differ from the chronological age.
The objective is now to identify the precise mechanisms which modify during these two periods and to determine whether certain interventions could one day be adapted to age and sex. But caution remains in order. This study shows biological trajectories; it does not prove that a particular intervention would slow down immune aging or prevent a disease.
It nevertheless opens up a major avenue: rather than considering aging as a uniform phenomenon,
medicine could learn to identify windows of vulnerability specific to each person.
A new way of looking at age: no longer as a regular slope, but as a succession of biological changes, some of which could perhaps be better anticipated.