Immunosenescence
The ageing of the immune system that reduces defences and increases inflammation
Definition
Immunosenescence is the progressive deterioration of the immune system with age, characterised by: thymic involution (the thymus, where T lymphocytes mature, progressively atrophies from puberty), reduction of the naïve T lymphocyte repertoire, clonal expansion of senescent memory T lymphocytes (CD28null), decline of NK cell and neutrophil function, and imbalance between innate and adaptive immunity. It is one of the central mechanisms behind the age-related increase in infectious mortality, cancer, and autoimmune diseases.
Detailed explanation
Components of immunosenescence:
Thymic involution: the thymus weighs 30-40 g at birth and <5 g at age 60; naïve T-lymphocyte production drops 90%. Without new naïve T cells, the adaptive immune system loses capacity to respond to unknown antigens. CD28null expansion: a CD8+ T-cell subset that has lost the CD28 co-stimulator, are senescent, secrete inflammatory cytokines, and are refractory to apoptosis. Their proportion increases dramatically with age and predicts mortality. CMV reactivation: cytomegalovirus, latent in >80% of adults, subclinically reactivates with ageing, consuming 10-30% of the memory T-cell repertoire.
Immunosenescence produces 'inflammaging' — paradoxical chronic low-grade inflammation (more inflammation alongside less effective response). This manifests clinically as poorer vaccine response, increased susceptibility to severe infections (mortality from flu and COVID-19 increases exponentially with age), higher cancer incidence, latent virus reactivation, and increased autoimmunity.
Investigated interventions to reverse/attenuate immunosenescence: the TRIIM trial (Fahy 2019) with GH + DHEA + metformin showed thymic regeneration measured by MRI and reduction of epigenetic age; FOX01-Wnt pathway, low-dose rapamycin (Mannick 2014, improves vaccine response in elderly), stem cell therapy, selective senolytic elimination of CD28null cells.
Scientific sources
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