Objective:

To map how immune profiles change across adulthood and interpret age-related differences in immune responses.

Key Findings:

• Non-linear, age-associated transcriptional reprogramming in T cells was observed.
• Persistent age-associated differences in circulating protein profiles were noted, with increases in markers like CXCL17, WNT9A, and GDF15.
• Classic inflammatory cytokines were not elevated before advanced age.
• The RNA Age Metric (RAM) reflects immune age and remains consistently higher in older adults.
• Naïve CD8 cells decreased while age-associated B cells increased with age.

Interpretation:

Age significantly impacts immune measurements, including protein levels, immune cell composition, and antibody responses post-vaccination, often without signs of inflammation.

Limitations:

• The study primarily focused on healthy adults, limiting generalizability to those with chronic conditions.
• Longitudinal data was limited to a subset of participants.

Conclusion:

Using age-adjusted reference data and combined molecular measures like the RNA Age Metric could enhance the interpretation of immune tests and improve vaccine response evaluations.