Single nucleotide polymorphisms: aging and diseases

Bessenyei, Beáta; Márka, Marietta; Urbán, László; Zeher, Margit; Semsei, Imre

doi:10.1007/s10522-004-2567-y

Cited by 34 publications

(17 citation statements)

References 74 publications

(66 reference statements)

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“…In this context, studying the interactions among more polymorphisms rather than a SNP is a power genetic approach in order to discovery more ''robust'' genes related to the longevity or the appearance of age-related diseases [15]. However, the study of a large number of genes is impracticable because hundreds of thousands of SNPs may need to be simultaneously analysed in order to warrant the goal of finding ''robust'' genes for the longevity.…”

Section: Zinc-hsp70 Gene Interactionmentioning

confidence: 99%

Zinc–gene interaction related to inflammatory/immune response in ageing

Mocchegiani

Malavolta

2008

Genes Nutr

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The pivotal role played by zinc-gene interaction in affecting some relevant cytokines (IL-6 and TNF-a) and heat shock proteins (HSP70-2) in ageing, successful ageing (nonagenarians) and the most common age-related diseases, such as atherosclerosis and infections, is now recognized. The polymorphisms of genes codifying proteins related to the inflammation are predictive on one hand in longevity, on the other hand they are associated with atherosclerosis or severe infections. Since the health lifespan has a strong genetic component, which in turn also affected by nutritional factors like zinc, the association of these polymorphisms with innate immune response, zinc ion bioavailability and Metallothioneins (MT) homeostasis is an useful tool to unravel the role played by zinc-gene interactions in longevity, especially due to the inability of MT in zinc release in ageing and chronic inflammation. In ageing, this last fact leads to depressed innate immune response for host defence. In contrast, in very old age the inflammation is lower with subsequent more zinc ion bioavailability, less MT gene expression and satisfactory innate immunity. Therefore, the zinc-gene (IL-6, TNF-a, Hsp70-2) interactions, via MT homeostasis, are crucial to achieve successful ageing. Human genes and longevityAgeing is a universal phenomenon that affects nearly all of animal species. According to Helfand and Rogina [69], ageing can be characterized as: (1) an inevitable consequence of being a multicellular organism; (2) associated with a random, passive decline in function; (3) leading to a global loss of homeostasis over time and (4) mortality increasing with ageing. Evolutionary studies on ageing have drawn the attention on the importance of the genetic mechanisms involved in somatic maintenance and repair that secure longevity [82]. Evidence from model organisms has indicated that subtle variation in the genes can dramatically influence lifespan. However, findings on potential candidate genetic mechanisms determining ageing and lifespan in model organisms are far to explain variations in human populations because phenotypes are critically dependent on the setting in which genes are expressed, while laboratory conditions and modern environments are markedly dissimilar [86]. Genetic analysis of human ageing is mainly approached by searching the genetic basis of susceptibility to major geriatric disorders or the allelic contributions to exceptionally long life span. It is just thanks to these last studies in centenarians populations that several candidate longevity genes or pathways including PON1 [19,130], IGF1/insulin pathway [84,120], elements of lipid metabolism [12], stress response [34] and inflammatory response have been identified [53].Genes related to inflammation and stress response, in particular the pro-inflammatory cytokines IL-1, IL-6, TNFalpha, the anti-inflammatory cytokine IL-10, the HSP70 chaperones and the regulators of trace elements homeostasis, metallothioneins (MT), seem particularly relevant taking into accoun...

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Section: Zinc-hsp70 Gene Interactionmentioning

confidence: 99%

Zinc–gene interaction related to inflammatory/immune response in ageing

Mocchegiani

Malavolta

2008

Genes Nutr

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“…The differences in average life span and susceptibility to certain diseases among the population have spurred researchers to use single nucleotide polymorphisms (SNPs) in whole genome association studies in aging and age-related disorders. This approach could aid in narrowing down to specific genes that are more important than others in determining the life span (Bessenyei et al 2004). …”

Section: Genomic Analysis Pertaining To Agingmentioning

confidence: 99%

Bioinformatics and Proteomics Approaches for Aging Research

et al. 2005

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Aging is a natural phenomenon that affects the entire physiology of an organism. Elucidating the molecular mechanisms underlying this complex process remains a major challenge today. Humans make poor models for research into aging because of their long life span. Thus, most of the current knowledge is through studies conducted in lower organisms. Large differences in life spans make it difficult to extrapolate the results of experiments carried out in model organisms to humans. Recent advances in genomic and proteomic technologies now permit generation of data pertaining to aging on a large-scale. In addition, several web-based community resources and databases are available that provide easy access to the available data. Use of bioinformatics and systems biology type of approaches provide a framework to start dissecting this complex biological phenomenon. Here, we discuss various genomic, transcriptomic and proteomic approaches that have the potential to provide a comprehensive mechanistic insight into the aging process.

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“…Alterations in DNA sequences may cause changes in binding sites of transcription factors, or affect its binding kinetics. Thus, a single nucleotide polymorphism (SNP) in a promoter element may affect gene transcription and, therefore, gene function [16]. In the present study, we investigated whether one or more SNPs in the promoter region of the SYK gene may affect its expression and, if so, whether such SNPs may be related to the development of CRC.…”

Section: Introductionmentioning

confidence: 99%