Title:T Cell Replicative Senescence in Human Aging
Volume: 19
Issue: 9
Author(s): Jennifer P. Chou and Rita B. Effros
Affiliation:
Keywords:
Telomere, telomerase, T cells, immune, human, latent infection, aging, HIV/AIDS, immunosenescence, replicative senescence
Abstract: The decline of the immune system appears to be an intractable consequence of aging, leading to increased susceptibility to infections,
reduced effectiveness of vaccination and higher incidences of many diseases including osteoporosis and cancer in the elderly.
These outcomes can be attributed, at least in part, to a phenomenon known as T cell replicative senescence, a terminal state characterized
by dysregulated immune function, loss of the CD28 costimulatory molecule, shortened telomeres and elevated production of proinflammatory
cytokines. Senescent CD8 T cells, which accumulate in the elderly, have been shown to frequently bear antigen specificity
against cytomegalovirus (CMV), suggesting that this common and persistent infection may drive immune senescence and result in functional
and phenotypic changes to the T cell repertoire. Senescent T cells have also been identified in patients with certain cancers, autoimmune
diseases and chronic infections, such as HIV. This review discusses the in vivo and in vitro evidence for the contribution of CD8
T cell replicative senescence to a plethora of age-related pathologies and a few possible therapeutic avenues to delay or prevent this differentiative
end-state in T cells. The age-associated remodeling of the immune system, through accumulation of senescent T cells has farreaching
consequences on the individual and society alike, for the current healthcare system needs to meet the urgent demands of the increasing
proportions of the elderly in the US and abroad.
