An Immune Risk Phenotype, Cognitive Impairment, and Survival in Very Late Life: Impact of Allostatic Load in Swedish Octogenarian and Nonagenarian Humans

Wikby, Anders; Ferguson, Frederick G.; Forsey, Rosalyn; Thompson, Julie M.; Strindhall, Jan; Löfgren, Sture; Nilsson, Bengt J.; Ernerudh, Jan; Pawelec, Graham; Johansson, Boo

doi:10.1093/gerona/60.5.556

Cited by 367 publications

(257 citation statements)

References 56 publications

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“…2a). This significantly greater percentage of memory cells and tendency for fewer naïve cells is also exactly a characteristic of the IRP seen in very elderly Swedes (Wikby et al 2005). The frequency distributions of CD8+ cells with other phenotypes in young and elderly people were as follows: significantly more memory CD45RO+CD27− cells in the elderly (Fig.…”

Section: T Cellsmentioning

confidence: 60%

Aging affects the proportions of T and B cells in a group of elderly men in a developing country—a pilot study from Pakistan

Alam

Goldeck

Larbi

et al. 2012

AGE

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Section: T Cellsmentioning

confidence: 60%

Aging affects the proportions of T and B cells in a group of elderly men in a developing country—a pilot study from Pakistan

Alam

Goldeck

Larbi

et al. 2012

AGE

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“…23,41,96,97,116). Within this scenario, the age-related changes in body composition (loss of muscle/bone mass and increase of fat mass) (84), insulin growth factor 1/insulin pathway (36), as well as inflammatory phenomena occurring in the central nervous system are also emerging as critical influences on the development of frailty and major age-related diseases (59,121,124).…”

mentioning

confidence: 99%

Aging of the Immune System as a Prognostic Factor for Human Longevity

et al. 2008

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“…Of these, the best investigated and the most pronounced are the changes affecting aging T cells. Age-related changes were seen in T cell subset representation and T cell diversity in humans (1-3) and experimental animals (4,5) and have been associated with higher mortality in the aging humans (6,7). Moreover, impaired T cell activation has been documented in senescent rodent and human T cells (8)(9)(10)(11).…”

mentioning

confidence: 99%

Dramatic increase in naïve T cell turnover is linked to loss of naïve T cells from old primates

Čičin‐Šain¹,

Messaoudi²,

Park

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

124

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The loss of naïve T cells is a hallmark of immune aging. Although thymic involution is a primary driver of this naïve T cell loss, less is known about the contribution of other mechanisms to the depletion of naïve T cells in aging primates. We examined the role of homeostatic cycling and proliferative expansion in different T cell subsets of aging rhesus macaques (RM). BrdU incorporation and the expression of the G1-M marker Ki-67 were elevated in peripheral naïve CD4 and even more markedly in the naïve CD8 T cells of old, but not young adult, RM. Proliferating naïve cells did not accumulate in old animals. Rather, the relative size of the naïve CD8 T cell compartment correlated inversely to its proliferation rate. Likewise, T cell receptor diversity decreased in individuals with elevated naïve CD8 T cell proliferation. This apparent contradiction was explained by a significant increase in turnover concomitant with the naïve pool loss. The turnover increased exponentially when the naïve CD8 T cell pool decreased below 4% of total blood CD8 cells. These results link the shrinking naïve T cell pool with a dramatic increase in homeostatic turnover, which has the potential to exacerbate the progressive exhaustion of the naïve pool and constrict the T cell repertoire. Thus, homeostatic T cell proliferation exhibits temporal antagonistic pleiotropy, being beneficial to T cell maintenance in adulthood but detrimental to the long-term T cell maintenance in aging individuals.aging ͉ CD8 ͉ homeostasis T he immune system undergoes dramatic age-related changes in both structure and function. Of these, the best investigated and the most pronounced are the changes affecting aging T cells. Age-related changes were seen in T cell subset representation and T cell diversity in humans (1-3) and experimental animals (4, 5) and have been associated with higher mortality in the aging humans (6, 7). Moreover, impaired T cell activation has been documented in senescent rodent and human T cells (8)(9)(10)(11). Although the molecular lesions in T cell activation have been thoroughly studied, the picture of the age-related dysregulation of T cell populations is still emerging.Optimal protection against new or evolving pathogens requires a reserve of naïve T cells. However, naïve T cell production is reduced in old age because of the involution of the thymus. The maintenance of the naïve T cell compartment is further challenged by the lifelong consumption of naïve cells that respond to acute and persistent infections and become memory T cells. With age, the balance between naïve and antigenselected memory cells changes in favor of the latter, reducing the diversity of T cell receptors (TCRs). In fact, the aging naïve T cell population is reduced in both relative and absolute terms, suggesting that homeostatic mechanisms that maintain the size and the clonal diversity of the T cell repertoire progressively break down (12)(13)(14).T cells can also be replenished by extrathymic mechanisms, which rely on homeostatic proliferation in the absenc...

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An Immune Risk Phenotype, Cognitive Impairment, and Survival in Very Late Life: Impact of Allostatic Load in Swedish Octogenarian and Nonagenarian Humans

Cited by 367 publications

References 56 publications

Aging affects the proportions of T and B cells in a group of elderly men in a developing country—a pilot study from Pakistan

Aging affects the proportions of T and B cells in a group of elderly men in a developing country—a pilot study from Pakistan

Aging of the Immune System as a Prognostic Factor for Human Longevity

Dramatic increase in naïve T cell turnover is linked to loss of naïve T cells from old primates

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