Dataset Information

SIRT1 Polymorphisms and Serum-Induced SIRT1 Protein Expression in Aging and Frailty: The CHAMP Study.

ABSTRACT: The nutrient sensing protein, SIRT1 influences aging and nutritional interventions such as caloric restriction in animals, however, the role of SIRT1 in human aging remains unclear. Here, the role of SIRT1 single-nucleotide polymorphisms (SNPs) and serum-induced SIRT1 protein expression (a novel assay that detects circulating factors that influence SIRT1 expression in vitro) were studied in the Concord Health and Ageing in Men Project (CHAMP), a prospective cohort of community dwelling men aged 70 years and older. Serum-induced SIRT1 expression was not associated with age or mortality, however participants within the lowest quintile were less likely to be frail (odds ratio (OR) 0.34, 95% confidence interval (CI) 0.17-0.69, N = 1,309). Serum-induced SIRT1 expression was associated with some markers of body composition and nutrition (height, weight, body fat and lean % mass, albumin, and cholesterol) but not disease. SIRT1 SNPs rs2273773, rs3740051, and rs3758391 showed no association with age, frailty, or mortality but were associated with weight, height, body fat and lean, and albumin levels. There were some weak associations between SIRT1 SNPs and arthritis, heart attack, deafness, and cognitive impairment. There was no association between SIRT1 SNPs and the serum-induced SIRT1 assay. SIRT1 SNPs and serum-induced SIRT1 expression in older men may be more closely associated with nutrition and body composition than aging and age-related conditions.

SUBMITTER: Razi S

PROVIDER: S-EPMC6279142 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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SIRT1 Polymorphisms and Serum-Induced SIRT1 Protein Expression in Aging and Frailty: The CHAMP Study.

Razi Shajjia S Cogger Victoria C VC Kennerson Marina M Benson Vicky L VL McMahon Aisling C AC Blyth Fiona M FM Handelsman David J DJ Seibel Markus J MJ Hirani Vasant V Naganathan Vasikaran V Waite Louise L de Cabo Rafael R Cumming Robert G RG Le Couteur David G DG

The journals of gerontology. Series A, Biological sciences and medical sciences 20170701 7

The nutrient sensing protein, SIRT1 influences aging and nutritional interventions such as caloric restriction in animals, however, the role of SIRT1 in human aging remains unclear. Here, the role of SIRT1 single-nucleotide polymorphisms (SNPs) and serum-induced SIRT1 protein expression (a novel assay that detects circulating factors that influence SIRT1 expression in vitro) were studied in the Concord Health and Ageing in Men Project (CHAMP), a prospective cohort of community dwelling men aged ...[more]

PMID: 28329314

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Project description:BackgroundSIRT1 is a multifunctional protein, possibly essential in tumorigenesis pathways, which can act both as a tumor promoter and tumor suppressor depending on the oncogenes, specific to particular tumors. Pathogenesis of laryngeal cancer is multifactorial and the association of SIRT1 expression with the clinical characteristics and prognosis of LSCC has not been fully identified.ObjectivesThe study aimed to evaluate associations between single gene nucleotide polymorphisms (SNPs) of SIRT1 (rs3818292, rs3758391, and rs7895833), serum SIRT1 levels, and 5-year survival rate in patients with laryngeal squamous cell carcinoma (LSCC).MethodsThe study involved 302 patients with LSCC and 409 healthy control subjects. The genotyping of SNPs was performed using RT-PCR, and serum SIRT1 levels were determined by the ELISA method.ResultsOur study found significant differences in genotype distributions of SIRT1 rs3758391 polymorphisms between the study groups. SIRT1 rs3758391 T/T genotype was associated with the increased LSCC development odds (OR = 1.960 95% CI = 1.028-3.737; p= 0.041). Carriers of SIRT1 rs3758391 T/T genotype had statistically significantly increased odds of LSCC development into advanced stages under the codominant and recessive genetic models (OR = 2.387 95% CI = 1.091-5.222; p= 0.029 and OR = 2.287 95% CI = 1.070-4.888; p= 0.033, respectively). There were no statistically significant differences in serum SIRT1 levels between the LSCC and control groups. However, LSCC patients with SIRT1 rs3818292 AG genotype demonstrated a tendency to significantly lower SIRT1 serum levels than controls (p= 0.034). No statistically significant associations between SIRT1 (rs3818292, rs3758391, and rs7895833) SNPs and the 5-year survival rate of LSCC patients were found.ConclusionThe present study indicated a statistically significant association between the SIRT1 rs3758391 T/T genotype and increased LSCC development odds. LSCC patients with SIRT1 rs3818292 AG genotype showed a tendency to manifest with lower SIRT1 serum levels. No associations between SIRT1 SNPs and the 5-year survival rate of LSCC patients were detected.

Project description:BackgroundFrailty remains a challenge in the aging research area with a number of gaps in knowledge still to be filled. Frailty seems to behave as a network, and in silico evidence is available on this matter. Having in vivo evidence that frailty behaves as a complex network was the main purpose of our study.MethodsData from the Mexican Health and Aging Study (main data 2012, mortality 2015) was used. Frailty was operationalized with a 35-deficit frailty index (FI). Analyzed nodes were the deficits plus death. The edges, linking those nodes were obtained through structural learning, and an undirected graph associated with a discrete probabilistic graphical model (Markov network) was derived. Two algorithms, hill-climbing (hc) and Peter and Clark (PC), were used to derive the graph structure. Analyses were performed for the whole population and tertiles of the total FI score.ResultsFrom the total sample of 10,983 adults aged 50 or older, 43.8% were women, and the mean age was 64.6 years (SD = 9.3). The number of connections increased according to the tertile level of the FI score. As the FI score raised, groups of interconnected deficits increased and how the nodes are connected changed.ConclusionsFrailty phenomenon can be modeled using a Bayesian network. Using the full sample, the most central nodes were self-report of health (most connected node) and difficulty walking a block, and all deficits related to mobility were very interconnected. When frailty levels are considered, the most connected nodes differ, but are related with vitality, mainly at lower frailty levels. We derived that not all deficits are equally related since clusters of very related deficits and non-connected deficits were obtained, which might be considered in the construction of the FI score. Further research should aim to identify the nature of all observed interactions, which might allow the development of specific interventions to mitigate the consequences of frailty in older adults.

Dataset Information

SIRT1 Polymorphisms and Serum-Induced SIRT1 Protein Expression in Aging and Frailty: The CHAMP Study.

Publications

SIRT1 Polymorphisms and Serum-Induced SIRT1 Protein Expression in Aging and Frailty: The CHAMP Study.

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