Immunosenescence

Major features

• Thymic involution: the thymus shrinks from young adulthood; naive T-cell output collapses by age 60.
• T-cell repertoire contraction: fewer naive T cells, more memory cells, restricted antigen recognition.
• T-cell exhaustion: chronic stimulation produces dysfunctional cells.
• B-cell repertoire decline: fewer naive B cells, reduced antibody diversity.
• NK-cell shifts: more mature NK cells, less cytotoxic capacity.
• Innate-immune dysregulation: macrophage polarisation shifts; inflammasome over-activation.
• CMV expansion: in CMV-positive individuals (most older adults), CMV-specific T cells dominate the repertoire ("memory inflation").

Consequences

• Reduced vaccine responses (flu, pneumococcal, COVID).
• Higher infection severity and mortality.
• Cancer immunosurveillance loss.
• Inflammaging (chronic background inflammation).
• Reduced wound healing.

Interventions

• High-dose / adjuvanted vaccines for older adults (Fluzone HD, Shingrix, RSV vaccines).
• Senolytics (clearing exhausted/senescent immune cells).
• Sex-hormone modulation to retard thymic involution.
• FOXN1 gene therapy / thymic regeneration in pre-clinical work.
• Exercise preserves T-cell function.
• Caloric restriction preserves immune function in primates.

Related entries

Immunological theory, Inflammaging, Chronic inflammation, Senolytics.