The immune system in extreme longevity

Sansoni, Paolo; Vescovini, Rosanna; Fagnoni, Francesco; Biasini, Claudia; Zanni, Franco; Zanlari, Luca; Telera, Anna Rita; Lucchini, G.; Passeri, Giovanni; Monti, Daniela; Franceschi, Claudio; Passeri, M

doi:10.1016/j.exger.2007.06.008

Cited by 377 publications

(296 citation statements)

References 36 publications

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“…Immunosenescence has been related with several comorbidities, such as cardiovascular risk (Cesari et al 2003;Csiszar et al 2003), cancer (Shurin et al 2007;Sansoni et al 2008), or poor response to vaccines (Hainz et al 2005;Weinberger et al 2008). Despite the fact that mechanisms are still partially known, T cell exhaustion and systemic inflammation are depicted as important players.…”

Section: Discussionmentioning

confidence: 99%

Thymic function failure and C-reactive protein levels are independent predictors of all-cause mortality in healthy elderly humans

Ferrando‐Martínez

Romero-Sánchez

Solana

et al. 2011

AGE

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Relationship between thymic function and elderly survival has been suspected, despite the fact that formal proof is elusive due to technical limitations of thymic function-related markers. The newly described sj/β-TREC ratio allows now, by overcoming these limitations, an accurate measurement of thymic output in elderly humans. Thus, the aim of this study was to determine the impact of thymic function and inflammatory markers on healthy elderly human survival. Healthy volunteers (n=151), aged over 65, were asked to participate (CARRERITAS cohort). Subjects were excluded if diagnosed of dementia or, during the last 6 months, had clinical data of infection, hospital admission, antitumor therapy, or any treatment that could influence the immune status. Thymic function (sj/β-TREC ratio), CD4:CD8 T cell ratio, C-reactive protein, interleukin-6, and neutrophilia were determined from basal samples. All basal variables and age were associated with 2-year allcause mortality. Multivariate analysis showed that only thymic function and C-reactive protein were independently associated with time to death. In conclusion, we show, for the first time, the direct role of thymic function in human survival. C-reactive protein raise is also a marker of mortality in the healthy elderly, in a thymic-independent way.

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Section: Discussionmentioning

confidence: 99%

Thymic function failure and C-reactive protein levels are independent predictors of all-cause mortality in healthy elderly humans

Ferrando‐Martínez

Romero-Sánchez

Solana

et al. 2011

AGE

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“…Both groups have a naive T and B cell deficiency and increased NK cells compared with healthy young individuals (5,10,18), and CD95 expression on lymphocytes in vivo is increased in both A-T patients and the elderly and increases with normal aging (8,9). Interestingly, both A-T patients (19) and the elderly normal population (20) have low thymic output and elevated levels of oxidative stress, and both normal elderly (21,22) and some A-T patients show decreased production of specific Abs and decreased Ab responses to vaccination (4,23).…”

Section: Discussionmentioning

confidence: 99%

Classical Ataxia Telangiectasia Patients Have a Congenitally Aged Immune System with High Expression of CD95

Carney

Srinivasan

Moss

et al. 2012

The Journal of Immunology

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Ataxia-telangiectasia (A-T) is a rare neurodegenerative immunodeficiency disorder caused by mutations in the ataxia telangiectasia mutated gene. Patients commonly have lymphopenia and Ig-production abnormalities. We used multicolor flow cytometry and IL-7 ELISA to investigate the effect of A-T and age on the proportions of major lymphocyte subsets and their pattern of CD95 expression in relation to IL-7 levels in 15 classical A-T patients. We also analyzed the sensitivity of T cells from four classical A-T patients to CD95-mediated apoptosis using TUNEL and caspase-activation assays. Our results confirmed lymphopenia and a deficiency in naive T and B cells in A-T patients. In contrast to controls, the proportions of naive and memory T and B cell subsets in A-T patients did not vary in relation to age. There was no evidence of a deficiency in plasma IL-7 or IL-7R expression, and IL-7 concentration correlated positively with CD95 expression on CD4+ T cells. CD95 expression on unstimulated A-T lymphocytes was high, and the apoptotic sensitivity of activated naive and central memory T cells was increased. These findings show that the immunodeficiency in A-T patients may be described as congenitally aged and is not progressive. The naive cell deficiency is not related to a deficiency in IL-7 or its receptor. However, IL-7 may upregulate CD95 on A-T lymphocytes. High CD95 expression and increased apoptotic sensitivity of activated naive and central memory T cells may result in an increased level of CD95-mediated apoptosis, which could contribute to the congenital lymphopenia in A-T.

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“…The number of germinal centers is reduced, and there is a progressive loss of cell-mediated immunity, generally recognizable by a tendency toward the switch from Th1 vs. Th2 type response. [5] Moreover, in the aging process, and even in centenarians, there is a redistribution of monocytes, neutrophils, B and T subsets, and a quite normal number of T lymphocytes, even if these cells mostly show a memory phenotype, whereas a progressive reduction of virgin cells is observable, which makes the old individuals unable to respond to antigens not previously encountered. [6] Several studies have largely demonstrated an important role of genetic background in the achievement of advanced age.…”

Section: Introductionmentioning

confidence: 99%