Immune Aging Accelerates at 40 and 60, Research from Duke-NUS Shows

Human immune cells do not age at a steady rate. Instead, they undergo periods of accelerated aging, with major shifts in gene activity occurring around age 40 and again after 60, according to research published in Nature Communications and reported by Futurity.

Cellular Atlas Reveals Accelerated Aging Waves at 40 and 60

The analysis examined 3.8 million immune cells from nearly 2,000 healthy individuals aged 19 to 97. Researchers integrated publicly available datasets to build an immune atlas mapping genetic activity across the human lifespan. The data showed that the fundamental machinery behind cell function, specifically genes responsible for the synthesis of RNA and proteins, declines most sharply during these two peak aging windows.

Scientists at Duke-NUS Medical School led the study. Associate Professor Jacques Behmoaras, senior author of the study from the Centre of Biomedical Data Science, noted that aging is not a uniform decline. Understanding the drivers behind these distinct periods of rapid change could eventually help identify when interventions provide the greatest benefit, according to the findings.

T Cell Shifts and Sex Differences in Immune Aging

T cells, a type of white blood cell responsible for coordinating the body’s immune response, showed the most pronounced changes in gene activity during a person’s 40s. These same cells also act as the primary drivers for the second wave of changes observed after age 60. The specific subtypes of T cells undergoing transformation at age 40 differ from those shifting after 60, indicating specialized roles across different life stages.

The study also identified sex-specific changes in how these specialized T cells alter their activity. While women live longer, they face a higher prevalence of age and immune-related conditions. In Singapore, for instance, more than 600,000 people—roughly 11 percent of the population—suffer from autoimmune diseases such as lupus and rheumatoid arthritis, conditions heavily linked to both age and sex.

Professor Antonio Bertoletti from the Emerging Infectious Diseases Signature Research Programme at Duke-NUS pointed out that tracking these nonlinear changes helps explain increased susceptibility to infections and inflammatory conditions in older adults. Professor Sheemei Lok, Duke-NUS Interim Vice-Dean for Research, added that mapping these distinct trajectories shifts the medical approach away from a one-size-fits-all model toward precision maintenance of health.

AI Models Predict Biological Age for Sex-Tailored Interventions

Researchers used the study data to build artificial intelligence models capable of predicting biological age, which estimates the true age of the human body rather than chronological years. Investigators aim to use this predictive tool to isolate specific biological pathways and pinpoint exact time windows where sex-tailored interventions can be deployed.

The research received support from the National Research Foundation, Singapore, through the National Medical Research Council Open Fund-Large Collaborative Grant and Open Fund-Individual Research Grant. Additional administration and funding came from the Singapore Ministry of Health through the NMRC Office, MOH Holdings Pte Ltd, the Ministry of Education Singapore, the Agency for Science and Technology, and Duke-NUS.

Disclaimer: The information provided in this article is for educational and scientific communication purposes only and does not constitute medical advice. Always consult with a qualified healthcare provider regarding any medical condition, diagnosis, or treatment plan.