title: T cells and aging, January 2002 update.
abstract: Age-related changes in the immune system may contribute to morbidity and mortality due to decreased resistance to infection and, possibly, certain cancers in the aged. Many studies mostly performed in mice, rats and man but also including monkeys and dogs have established that age-associated immune decline is characterized by decreases in both humoral and cellular responses. The former may be largely a result of the latter, because observed changes both in the B cell germline-encoded repertoire and the age-associated decrease in somatic hypermutation of the B cell antigen receptors are now known to be critically affected by helper T cell aging. As antigen presenting cell (APC) function appears to be well-maintained in the elderly, this review will focus on the T cell. Factors contributing to T cell immunosenescence may include a) altered production of T cell progenitors (stem cell defects, stromal cell defects), b) decreased levels of newly-generated mature T cells (thymic involution), c) aging of resting immune cells, d) disrupted activation pathways in immune cells (stimulation via the T cell receptor for antigen, costimulation, apoptosis control), e) replicative senescence of clonally expanding cells. This review aims to consider the current state of knowledge on the scientific basis for and potential clinical relevance of those factors in immunosenescence in humans. Experiments in other species will be touched upon with the proviso that there are clearly differences between them, especially between humans and rodents, but exactly what those differences are is not completely clear. Given its potential importance and the increasing proportion of elderly people the world over, coupled with the realisation that whereas mortality is decreasing, morbidity may not be decreasing in parallel (1), a better understanding of the causes and impact of immunosenescence may offer the possibility of identifying where prevention or delay of onset, as well as therapeutic intervention, might be beneficial. Amelioration of the effects of dysregulated immune responses in the elderly by replacement therapy, supplementation therapy or other approaches may result in an enhancement of their quality of life, and significant reductions in the cost of medical care in old age.
authors: University of Tübingen, Center for Medical Research, ZMF, Waldhörnlestr. 22, D-72072 Tübingen, Germany. graham.pawelec@uni-tuebingen.de
authors: Graham
authors: G
authors: Pawelec
authors: Yvonne
authors: Y
authors: Barnett
authors: Ros
authors: R
authors: Forsey
authors: Daniela
authors: D
authors: Frasca
authors: Amiela
authors: A
authors: Globerson
authors: Julie
authors: J
authors: McLeod
authors: Calogero
authors: C
authors: Caruso
authors: Claudio
authors: C
authors: Franceschi
authors: Támás
authors: T
authors: Fülöp
authors: Sudhir
authors: S
authors: Gupta
authors: Erminia
authors: E
authors: Mariani
authors: Eugenio
authors: E
authors: Mocchegiani
authors: Rafael
authors: R
authors: Solana
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D016922:Cellular Senescence / Q000502:physiology*; D006801:Humans; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000502:physiology; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000502:physiology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000502:physiology
chemical_list: D011948:Receptors, Antigen, T-Cell