title: Telomere diminution as a cause of immune failure in old age: an unfashionable demurral.
abstract: The hypothesis that cellular proliferation leads to telomere shortening, which in turn leads to replicative failure, which in turn leads to a failure of immune function in aged individuals, is here evaluated against the published evidence about the nature and pace of immune decline in animals and humans. Although the evidence is strong that telomere shortening in late-passage human lymphocyte and non-lymphocytic cell lines induces a state in which the cells can no longer divide, there is no compelling evidence to suggest that replicative senescence of this kind is an important contributor to immune deficiency in old age. On the contrary, the accelerated pace of immune decline in mice and rats, whose telomeres are much longer than those of humans, argues strongly that the factors that pace age-dependent immune decline do not include telomere shortening. In addition, three subsidiary arguments - (a) the decline with age in naive T cell proliferation despite their relatively long telomeres; (b) the preservation of T cell proliferation in Werner's syndrome patients despite their cell lines' proclivity to replicative senescence in vitro; and (c) the ability of PMA and ionomycin to stimulate proliferation in T cells from old donors, but not in late-passage T celt lines - all support the conclusion that aging of the immune system in living animals is not a consequence of the kind of replicative senescence typically caused by short telomeres in vitro.
authors.affiliation: Department of Pathology, University of Michigan and Ann Arbor VA Medical Center, 48109-0940, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Miller
mesh_terms: D000375:Aging; D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D016922:Cellular Senescence; D006801:Humans; D007107:Immune System / Q000502:physiology*; D051379:Mice; D008954:Models, Biological; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D016615:Telomere / Q000378:metabolism* / Q000502:physiology*
chemical_list: D012333:RNA, Messenger