HLA Phenotypes in Healthy Aged Subjects

Papasteriades, C.; Boki, Kyriaki; Pappa, Helen; Aedonopoulos, St.; Papasteriadis, E.; Economidou, J.

doi:10.1159/000213847

Cited by 33 publications

(17 citation statements)

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“…This association appears to be gender‐specific. In fact, a Greek study showed a significant decrease of 8.1 AH in aged women 53–55 . So, the immune changes typical of the 8.1 AH should contribute to early morbidity and mortality in elderly women, who are more susceptible to autoimmune diseases than men, and to longevity in elderly men.…”

Section: Genetics Of Longevity: Role Of Hlamentioning

confidence: 98%

Immunogenetics, Gender, and Longevity

Candore

Balistreri

Listı́

et al. 2006

Annals of the New York Academy of Sciences

118

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In this article we discuss relevant data on aging, longevity, and gender with particular focus on inflammation gene polymorphisms which could affect an individual's chance to reach the extreme limit of human life. The present review is not an extensive revision of the literature, but rather an expert opinion based on selected data from the authors' laboratories. In 2000-2005 in the more developed regions, the life expectancy at birth is 71.9 years for men (78.3 in Japan) and 79.3 years for women (86.3 in Japan). Indeed, gender accounts for important differences in the prevalence of a variety of age-related diseases. Considering people of far-advanced age, demographic data document a clear-cut prevalence of females compared to males, suggesting that sex-specific mortality rates follow different trajectories during aging. In Italy this female/male ratio is relatively lower (about 5/1; F/M ratios are usually 5-6:1 in other developed countries), but significant differences have been observed between Italian regions in the distribution of centenarians by gender--from two women per man in the South to more than eight in certain regions in the North. Thus, a complex interaction of environmental, historical, and genetic factors, differently characterizing the various parts of Italy, likely plays an important role in determining the gender-specific probability of achieving longevity. This can be due to gender-specific cultural and anthropological characteristics of Italian society in the last 100 years. Age-related immunoinflammatory factors increase during proinflammatory status, and the frequency of pro/anti-inflammatory gene variants also show gender differences. There is some suggestion that people genetically predisposed to weak inflammatory activity may be at reduced chance of developing coronary heart disease (CHD) and, therefore, may achieve longer lifespan if they avoid serious life-threatening infectious disease thoroughout life. Thus, the pathogen burden, by interacting with host genotype, could determine the type and intensity of the immune-inflammatory response responsible for both proinflammatory status and CHD. These findings point to a strong relationship between the genetics of inflammation, successful aging, and the control of cardiovascular disease, but seem to suggest that the evidence for men is much stronger. The importance of these studies lies in the fact that half of the population (males) lives approximately 10% shorter lives than the other half (females). Understanding the different strategies that men and women seem to follow to achieve longevity may help us to comprehend better the basic phenomenon of aging and allow us to search for safe ways to increase male lifespan.

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Section: Genetics Of Longevity: Role Of Hlamentioning

confidence: 98%

Immunogenetics, Gender, and Longevity

Candore

Balistreri

Listı́

et al. 2006

Annals of the New York Academy of Sciences

118

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“…Lifespan is influenced by genetic makeup, most clearly demonstrated so far for the association between longevity and MHC type in mice (473) and possibly humans (230,(474)(475)(476). One mechanism accounting for this association may be a relationship between MHC alleles and rate of thymic involution (477).…”

Section: Predictors Of Mortality and Longevity (See Also Section 2)mentioning

confidence: 98%

T cells and aging update February 1999

Pawelec¹

1999

Front Biosci

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T cell immunosenescence 218effects of dysregulated immune responses in the elderly by supplementation 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. FACTORS CONTRIBUTING TO IMMUNO-SENESCENCE HematopoiesisDysregulated hematopoiesis is seen in elderly individuals, raising the possibility that this could contribute to altered immune function in the aged. Hematopoiesis in man may be compromised because of a severely reduced capacity to produce colony stimulating factors (44) and increased production of pro-inflammatory factors such as IL 6 (45), because lower numbers of progenitor cells are present in the BM (46) and because of an age-related decline in proliferative potential of putative haematopoietic stem cells (HSC) (47). In mice, the repopulating potential of murine fetal liver-derived HSC is higher than that of adult BM-derived stem cells (48), suggesting possible aging of the HSC themselves. Normal cells with shorter telomeres possess less remaining replicative capacity than those with longer telomeres (see section 5.2). Accordingly, HSC from adult BM were found to have shorter telomeres than fetal liver-derived or umbilical cord-derived stem cells, consistent with aging of HSC (49). Telomere lengths decreased on culture despite low level expression of telomerase in these cells (50,51), although the rate of basepair loss per population doubling of cells in culture was lower during the first two weeks, when telomerase was upregulated, than in the next two, when it was downregulated (52). The telomerase expressed is therefore functionally active but may not be able to completely maintain telomere length in aging HSC cells. True embryonic stem cells (ESC), on the other hand, which may really be immortal, do retain high levels of telomerase activity (53). On the other hand, ESC from telomerase-knockout mice show gradual telomere shortening over many population doublings (PD) resulting in slowing and eventual cessation of growth (54). Certain animals which do not downregulate telomerase manifest a permanent growth phase and little or no senescence (55,56).

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“…26 Thus, immune dysfunctions of AH 8.1 should contribute to early morbidity and mortality in elderly women, to more susceptibility to autoimmune diseases than men, and to longevity in elderly men. [2][3][4] These associations are gender-related, but it is not unexpected on the basis of available data on the genetics of longevity, showing that the association of longevity with particular alleles may be found only in one gender.…”

Section: Listi`et Almentioning

confidence: 99%

HLA and KIR Frequencies in Sicilian Centenarians

Listı́

Caruso

Colonna‐Romano

et al. 2010

Rejuvenation Research

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Several studies suggest that human longevity appears to be linked inextricably with optimal functioning of the immune system, suggesting that specific genetic determinants may reside in loci that regulate the immune response, as human leukocyte antigen (HLA) and killer cell immunoglobulin-like receptor (KIR) genes. It has been suggested that longevity is associated with positive selection of alleles (i.e., HLA-DR11) or haplotypes (i.e., HLA-B8,DR3) that confer resistance to infectious disease(s). On the other hand, the cytolytic activity of natural killer (NK) cells is controlled by activating and inhibitory cell-surface receptors, including KIR. The genetic diversity of the KIR loci with respect to successful aging has been analyzed only in one study performed in the Irish population. Although two KIR genes (2DS3, 2DL5) displayed an initial increased frequency in the aged group, the significance of this association was lost when repeated in a second cohort. We have evaluated by polymerase chain reaction-sequence-specific primers (PCR-SSP) HLA-DRB1 and KIR receptors=HLA ligands frequencies in centenarians and controls from Sicily. Our results demonstrate an increase of the HLA DRB1*18 allele in male centenarians ( p ¼ 0.0266, after Bonferroni correction). Concerning KIR, no significant difference was observed after Bonferroni correction. However, our findings suggest that HLA=KIR=longevity associations are population specific, being heavily affected by the population-specific genetic and environmental history. This kind of study is important to better understand aging and longevity, hence enhancing the planning of antiaging strategies.

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HLA Phenotypes in Healthy Aged Subjects

Cited by 33 publications

References 0 publications

Immunogenetics, Gender, and Longevity

Immunogenetics, Gender, and Longevity

T cells and aging update February 1999

HLA and KIR Frequencies in Sicilian Centenarians

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