Daan Pieren

18 Chapter 1 communicable diseases. For example, obesity is known to promote a pro- inflammatory cellular environment as it dysregulates the metabolic system and in turn this limits protective immune responses against infectious pathogens and vaccination [119,120]. Moreover, it is currently speculated that obesity may shift severe COVID-19 disease towards younger age groups in countries with high prevalence of obese younger individuals [121]. Additionally, inflammaging has been associated with increased prevalence of cardiovascular disease, diabetes mellitus, and autoimmune disease [122]. Recent studies suggest that senescent T cells may be a cause for the occurrence of inflammaging by secretion of SASP-related proteins [123]. CD4 + T cells of older adults have been shown to produce higher levels of pro-inflammatory cytokines, thereby contributing to inflammaging [124]. Moreover, T cells have recently been found to be an important driving factor in the development of inflammaging in mice [125]. T cells with a mitochondrial dysfunction were found to induce a pro-inflammatory cytokine storm that consisted of increased serum levels of IFN- γ , TNF- α , and IL-6. In turn, these cytokines were found to drive cellular senescence of peripheral tissues which could in part be reversed by blocking of TNF- α . Thus, these studies suggest that T cells may be a driving factor of inflammaging, a process that is linked to susceptibility to both communicable and non-communicable diseases. To conclude, T cells have a central role in increased susceptibility to infectious disease and reduced responsiveness to vaccination found in older adults. Elucidating the underlying mechanisms for diminished T-cell responses with age in the context of infection and vaccination is one of the most important aims in the field of aging of the immune system. Identifying changes that occur to T cells with age may drive future research on potential interventions to promote T-cell responses in older adults.