Immune aging accelerates around 40 and 60, with key differences between men and women, according to new research.
The analysis of 3.8 million immune cells from nearly 2,000 people reveals distinct waves of immune aging and sex-specific changes that may help explain differences in age-related and autoimmune diseases.
It’s one of the biggest mysteries of age-related research: despite living longer, women are more likely than men to develop age and immune-related conditions, yet the biological reasons behind these differences remain poorly understood.
Scientists at Duke-NUS Medical School have shed new light on this by integrating and analyzing large-scale immune-cell datasets to uncover how healthy immune cells change differently in men and women as they age. These findings, recently published in Nature Communications, pave the way for more personalized treatments for age and immune-related diseases, taking into account a patient’s sex and age.
More than 600,000 people in Singapore, or about 11% of the population, suffer from autoimmune diseases such as lupus and rheumatoid arthritis. These are conditions where the immune system turns against itself and attacks the body’s major organs. Autoimmune conditions are strongly related to both age and sex.
The scientists found that the immune cells circulating in our bloodstream do not age at a steady pace. Instead, they undergo periods of accelerated aging, with major shifts in gene activity occurring around age 40 and again after 60. The analyses showed that the fundamental machinery behind cell function (i.e. genes responsible for synthesis of RNA and proteins) decline most at these two aging peak points.
The authors studied how each immune cell type ages in men and women across a heathy lifespan. They found that T cells, a type of white blood cell that helps our immune system fight germs, showed the most pronounced changes in gene activity around people’s 40s. This reflects their central role in coordinating the body’s immune response and their sensitivity to the effects of aging.
T cells were also predominantly found to be the main drivers of a second wave of changes after age 60. Interestingly, the type of T cells that change profoundly at 40s and 60s is different, suggesting their specialized roles at different stages of life. In addition, the way these specialized T cells change their activity throughout life show differences between man and women.
“We tend to think of aging as a gradual process, but our findings show that the immune system does not simply decline at a steady rate. Instead, we see distinct periods of rapid change, particularly around 40 and again after 60, with T cells playing a major role. Understanding what drives these windows of immune aging could eventually help us identify when, and for whom, interventions may have the greatest benefit. It could also shed light on why some autoimmune conditions disproportionately affect women,” explains senior author of the study, Associate Professor Jacques Behmoaras, from the Centre of Biomedical Data Science at Duke-NUS Medical School.
One of the largest and most diverse of its kind, the study examined the genetic activity of 3.8 million individual immune cells from nearly 2,000 healthy people aged 19 to 97. Among these people were those of Asian ethnicity, including Singaporeans. The cell data was collated from various publicly available research datasets and integrated to create an immune atlas.
“Our findings build on previous evidence that T cells are among the immune cells most affected by aging. Understanding what drives these nonlinear changes in T cells over time will be an important next step. Changes in T cell function may help explain why older adults are more susceptible to infections and inflammatory conditions,” says Professor Antonio Bertoletti from the Emerging Infectious Diseases Signature Research Programme in Duke-NUS Medical School, who is one of the authors of the study.
The study was conducted at Duke-NUS’ Centre of Biomedical Data Science in collaboration with the school’s Signature Research Programmes in Cardiovascular and Metabolic Disorders, Cancer and Stem Cell Biology, and Emerging Infectious Diseases. The research also involved partners from NUS Yong Loo Lin School of Medicine.
“The study gives us a more detailed map of how the human immune system changes across the lifespan, and importantly, how those trajectories differ between men and women. That knowledge is fundamental if we want to move away from treating aging as a one-size-fits-all approach and move towards more precise approaches to maintaining health as people grow older,” says Professor Sheemei Lok, Duke-NUS’ Interim Vice-Dean for Research.
The scientists used the study data to build AI models that would predict biological age—an estimation of the “true age” of the human body that may differ from one’s actual age. With this tool, the scientists hope to do more research on specific biological pathways and time windows where interventions could be tailored by sex.
This research was supported by the National Research Foundation, Singapore (NRF) under the National Medical Research Council (NMRC) Open Fund-Large Collaborative Grant and Open Fund-Individual Research Grant and administered by the Singapore Ministry of Health through the NMRC Office, MOH Holdings Pte Ltd, Ministry of Education Singapore, Agency for Science and Technology, and Duke-NUS.
Source: Duke-NUS
