Study Maps Early Immune Aging and Its Impact on Vaccine Response

A study published in Nature presents a detailed analysis of how the human immune system changes with age, showing that key aspects of immune aging begin earlier than previously documented. Researchers from the Allen Institute for Immunology and collaborators analyzed blood samples from over 300 healthy adults aged 25 to 90, using single-cell RNA sequencing, proteomics, and flow cytometry to profile immune function across age groups.

A subset of 96 individuals was followed longitudinally for two years, including during seasonal influenza vaccination. The study found that early-differentiated T cells—particularly naïve and central memory T cells—undergo progressive transcriptional reprogramming starting in midlife, between ages 55 and 65. These age-related changes occurred in the absence of systemic inflammation or chronic cytomegalovirus (CMV) infection.

The analysis identified a shift in memory T cells toward a T helper 2 (TH2) profile, characterized by increased expression of the transcription factor GATA3 and elevated IL-4 production. This TH2 bias was associated with altered B cell responses to influenza vaccination, including reduced antibody class switching and lower levels of strain-specific IgG antibodies, particularly for the influenza B/Phuket strain.

Although CMV infection altered the composition of certain T cell and NK cell subsets, it did not influence the observed age-related transcriptional changes. These findings suggest that CMV does not drive the early transcriptional features of immune aging.

The study also applied a composite RNA Age Metric (RAM) to quantify transcriptional aging across immune subsets. RAM increased with age and was consistent across independent cohorts. Elevated RAM scores were observed in adults at risk for rheumatoid arthritis, indicating a potential link between early immune aging and disease susceptibility.

Overall, the results indicate that specific immune cell types begin to exhibit stable, age-related changes in transcriptional programming before age 65. These changes may affect vaccine responses and immune regulation in later life.