Longitudinal Multi-omic Immune Profiling Reveals Age-Related Immune Cell Dynamics in Healthy Adults

Area of Science:

• Immunology
• Gerontology
• Systems Biology

Background:

• Immune system function changes throughout human lifespan.
• Understanding age-related immune alterations is crucial for combating infections and diseases in older adults.
• Healthy aging involves dynamic immune system changes influenced by host-environment interactions.

Purpose of the Study:

• To investigate age-related changes in human peripheral immunity.
• To analyze immune cell composition and transcriptional states during homeostasis and vaccine response across different ages.
• To identify molecular mechanisms underlying immune dysregulation in healthy aging.

Main Methods:

• Multi-omic profiling including single-cell RNA sequencing (scRNA-seq), proteomics, and flow cytometry.
• Analysis of peripheral blood mononuclear cells (PBMCs) from over 300 healthy adults.
• Longitudinal study of 96 young and older adults over two years with annual vaccination.

Main Results:

• T cells accumulate age-related transcriptional changes independently of inflammation.
• Older adults show impaired memory B cell responses to vaccination.
• A Th2-like state shift in memory CD4 T cells is linked to impaired B cell responses in older adults.

Conclusions:

• Human immune system exhibits significant age-related transcriptional changes, particularly in T cells.
• Aging-associated immune dysregulation involves shifts in T cell populations affecting B cell responses.
• The Immune Health Atlas provides a valuable resource for studying immune dynamics across the lifespan.