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A remarkable age-related increase in SIRT1 protein expression against oxidative stress in elderly: SIRT1 gene variants and longevity in human.

ABSTRACT: Aging is defined as the accumulation of progressive organ dysfunction. Controlling the rate of aging by clarifying the complex pathways has a significant clinical importance. Nowadays, sirtuins have become famous molecules for slowing aging and decreasing age-related disorders. In the present study, we analyzed the SIRT1 gene polymorphisms (rs7895833 A>G, rs7069102 C>G and rs2273773 C>T) and its relation with levels of SIRT1, eNOS, PON-1, cholesterol, TAS, TOS, and OSI to demonstrate the association between genetic variation in SIRT1 and phenotype at different ages in humans. We observed a significant increase in the SIRT1 level in older people and found a significant positive correlation between SIRT1 level and age in the overall studied population. The oldest people carrying AG genotypes for rs7895833 have the highest SIRT1 level suggesting an association between rs7895833 SNP and lifespan longevity. Older people have lower PON-1 levels than those of adults and children which may explain the high levels of SIRT1 protein as a compensatory mechanism for oxidative stress in the elderly. The eNOS protein level was significantly decreased in older people as compared to adults. There was no significant difference in the eNOS level between older people and children. The current study is the first to demonstrate age-related changes in SIRT1 levels in humans and it is important for a much better molecular understanding of the role of the longevity gene SIRT1 and its protein product in aging. It is also the first study presenting the association between SIRT1 expression in older people and rs7895833 in SIRT1 gene.

SUBMITTER: Kilic U

PROVIDER: S-EPMC4365019 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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A remarkable age-related increase in SIRT1 protein expression against oxidative stress in elderly: SIRT1 gene variants and longevity in human.

Kilic Ulkan U Gok Ozlem O Erenberk Ufuk U Dundaroz Mehmet Rusen MR Torun Emel E Kucukardali Yasar Y Elibol-Can Birsen B Uysal Omer O Dundar Tolga T

PloS one 20150318 3

Aging is defined as the accumulation of progressive organ dysfunction. Controlling the rate of aging by clarifying the complex pathways has a significant clinical importance. Nowadays, sirtuins have become famous molecules for slowing aging and decreasing age-related disorders. In the present study, we analyzed the SIRT1 gene polymorphisms (rs7895833 A>G, rs7069102 C>G and rs2273773 C>T) and its relation with levels of SIRT1, eNOS, PON-1, cholesterol, TAS, TOS, and OSI to demonstrate the associa ...[more]

PMID: 25785999

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Project description:Characterization of the human microbiota is providing new insightsinto the complexity of host–parasite–bacterium relationships. Amoebiasis (an intestinal infection affecting a large proportion of the population in many countries worldwide) is caused by the amoebic parasite Entamoeba histolytica. During amoebiasis, the parasite encounters several types of stress as a result of the host’s response to infection. Given that E. histolytica phagocytises bacteria in the intestinal lumen, we hypothesized that enteric bacteria can influence the course of an amoebic infection. Hence, we used live Escherichia coli O55 as a pertinent model of the bacterial community’s contribution to amoebic responses during host- induced stress. By measuring amoebic survival, we found that live E. coli protected E. histolytica against oxidative stress (OS) but not against nitrosative stress. E. coli– associated protection is correlated with massive transcriptionalchanges in amoebic genes acquired through lateral transfer from the bacterial kingdom, including genes coding for proteinscontaining leucine-rich repeat (LRR) motifs. The transcriptome profile triggered by OS and E. coli was also observed with other enteric bacteria, including pathogens and non-pathogens. In contrast, exposure to a probiotic resulted in a different transcriptome profile. The present study shows that OS and live bacteria together modulate 84 of E. histolytica’s 137 LRR protein genes. The LRR proteins are involvedin protein-ligand and protein-protein interactions – especially in proteins that interact with bacteria as part of the innate immune response in mammals and plants, such as Toll-like receptors. The structural and functional homology of LRRs and TLRs identified here suggest that despite its old age in evolutionary terms, the protozoan E. histolytica displays key characteristics of higher eukaryotes’ innate immune systems. We conclude that components of innate immunity existed in the common ancestor of plants and animals

Dataset Information

A remarkable age-related increase in SIRT1 protein expression against oxidative stress in elderly: SIRT1 gene variants and longevity in human.

Publications

A remarkable age-related increase in SIRT1 protein expression against oxidative stress in elderly: SIRT1 gene variants and longevity in human.

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