Study reveals how our immune system transforms across a lifetime—unlocking the potential for predicting disease risk and optimizing health before symptoms appear.
Resource: Integrating single-cell RNA and T cell/B cell receptor sequencing with mass cytometry reveals dynamic trajectories of human peripheral immune cells from birth to old age. Image Credit: Lightspring / Shutterstock
What if doctors could measure your immune system’s age just as easily as your chronological age? Scientists have taken a major step in that direction, mapping how our immune system evolves from birth to old age.
In a recent study published in the journal Nature Immunology, a research team from China analyzed immune cells across the human lifespan, identifying key changes that shape health, disease resistance, and aging. The findings could pave the way for personalized healthcare, predicting immune health and guiding interventions before illness strikes.
The science behind immune aging
The immune system is a complex network of cells that protects the body from infections, cancers, and other diseases. While scientists know that immunity changes with age, much of this process remains a mystery. Infants are born with an underdeveloped immune system, relying on maternal antibodies for protection. As they grow, exposure to pathogens and vaccines helps shape their immune defenses. In adulthood, the immune system is robust, but as people age, it gradually weakens, increasing susceptibility to infections, autoimmune diseases, and even cancer.
Until now, most studies on immune aging have focused on specific age groups rather than the entire lifespan. Advances in single-cell technologies have made it possible to study immune cells at an unprecedented level of detail, tracking changes in individual cell types across life stages. However, a comprehensive, high-resolution map of immune development covering infancy through old age was still missing.
About the Study
The present study aimed to fill that gap by providing a high-resolution look at how immune cells evolve throughout life and introducing an "immune age" model to predict immune health. Researchers analyzed blood samples from 220 healthy individuals ranging from newborns to nonagenarians and used single-cell ribonucleic acid sequencing (scRNA-seq) and T/B cell receptor sequencing to examine how immune cell composition, gene expression, and interactions change over time.
Additionally, they applied mass cytometry to validate protein-level changes in immune cells. By identifying 25 distinct immune cell subsets and tracking their distribution and function across 13 different age groups, the study captured age-related immune changes with greater precision than any previous research.
To analyze immune system evolution, the scientists categorized participants into eight life stages, ranging from newborns to the very elderly, covering various age categories, including toddlers, children, adolescents, young adults, middle-aged adults, and the elderly.
Furthermore, the study used statistical models, including machine learning tools, to develop an immune age prediction system that was externally validated using an additional cohort of 89 individuals, including both healthy participants and those with immune dysfunction. This model assessed immune health based on gene expression patterns, highlighting potential deviations that may indicate early signs of immune dysfunction.
Beyond identifying age-related shifts in immune cells, the researchers also examined how different immune cell types interact over time. They found that T cells undergo the most dramatic changes with age, particularly in how they communicate with other immune cells, a process critical for immune coordination and response.
Key findings: A changing immune landscape
The study found that immune aging is a continuous process influenced by life stages. In early life, immune cells undergo rapid development. One major discovery was a previously unrecognized subset of cytotoxic B cells, which express both B cell markers and cytotoxic genes (GNLY and NKG7). These cells were highly abundant in children but nearly absent in adults, suggesting they play a crucial role in early immune defense.
Similarly, mucosal-associated invariant T (MAIT) cells, which play a role in gut immunity, expanded during adolescence. The researchers linked this expansion to hormonal changes and microbiome shifts, which enhance MAIT cells' antimicrobial function and increase their TCR diversity.
T cells, the body’s primary defense against infections, showed the most drastic age-related changes. Naive T cells, which respond to new infections, declined steadily starting in young adulthood, while memory and effector T cells accumulated, leading to immune exhaustion. Interestingly, clonal expansion of CD8+ T cells—indicative of long-term immune activation—was observed at both ends of life. However, the functional roles of these clonally expanded cells differed significantly.
- In young children, CD8+ T cells exhibited strong cytotoxic activity, supporting the immune system’s ability to fight infections early in life.
- In older adults, these same expanded cells were linked to chronic inflammation and immune exhaustion, contributing to age-related immune decline.
One of the most important results was the development of the "immune age" model, which estimates a person’s immune health based on gene expression and cellular markers. This model was constructed using lifecycle-wide single-cell data and underwent external validation, confirming its ability to distinguish between healthy individuals and those with immune dysfunction. This tool could help detect early immune dysfunction, allowing for preventive interventions before symptoms appear.
Conclusions
Overall, the study provided a groundbreaking look at the changes in the immune system across a lifetime. By identifying key transitions in immune cell composition and function, the findings opened the door to predictive models that could revolutionize healthcare.
The researchers believe that with further improvements, the immune age model could become a valuable tool for diagnosing and preventing age-related diseases, ultimately improving health outcomes across generations. Additionally, the study reinforces the link between immune aging and chronic inflammation, a key driver of systemic aging that affects multiple organs, including the heart and liver.
Journal reference:
- Wang, Y., Li, R., Tong, R., Chen, T., Sun, M., Luo, L., Li, Z., Chen, Y., Zhao, Y., Zhang, C., Wei, L., Lin, W., Chen, H., Qian, K., Chen, A. F., Liu, J., Chen, L., Li, B., Wang, F., & Wang, L. (2025). Integrating single-cell RNA and T cell/B cell receptor sequencing with mass cytometry reveals dynamic trajectories of human peripheral immune cells from birth to old age. Nature Immunology. DOI: 10.1038/s41590024020596, https://www.nature.com/articles/s41590-024-02059-6