Dataset Information

Human longevity and 11p15.5: a study in 1321 centenarians.

ABSTRACT: The 11p15.5 chromosomal region (2.8 Mb) is of particular interest as it encloses five genes (HRAS1, SIRT3, TH, INS and IGF2), the variability of which was found to be associated with life extension by association studies. Mostly important, the above genes are homologous of genes that modulate lifespan in model organisms. We scanned the area in four European sample groups for a total of 1321 centenarians and 1140 younger subjects, who shared with centenarians ethnicity and geographical origin, with a set of 239 SNPs. No significant results (P<0.05) have been found on the earlier associated loci (ie, TH, IGF2, INS and HRAS1), and this study could not confirm the earlier findings on each of those genes. A meta-analysis was carried out on the SIRT3 SNP data; a total number of 2461 samples were included, but no positive association was found except for one SNP having a significant effect (rs939915). The same meta-analysis approach has been applied to the other 229 markers, and six SNPs have been found significant for the frequent genotype (rs4073591, DEAF1-rs4073590, KRTAP5-6-rs11040489, rs4930001, TSPAN32-rs800140 and rs16928120). This experience, although unable to confirm the earlier findings of the literature, highlights all the common difficulties of such studies in human longevity. Despite the rather negative findings presented here, the results derived from unprecedented studies involving such a large number of centenarians should be disseminated, thus contributing to set up adequate strategies to disentangle complex and likely heterogeneous phenotypes.

SUBMITTER: Lescai F

PROVIDER: S-EPMC2986679 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature

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Human longevity and 11p15.5: a study in 1321 centenarians.

Lescai Francesco F Blanché Helene H Nebel Almut A Beekman Marian M Sahbatou Mourad M Flachsbart Friederike F Slagboom Eline E Schreiber Stefan S Sorbi Sandro S Passarino Giuseppe G Franceschi Claudio C

European journal of human genetics : EJHG 20090415 11

The 11p15.5 chromosomal region (2.8 Mb) is of particular interest as it encloses five genes (HRAS1, SIRT3, TH, INS and IGF2), the variability of which was found to be associated with life extension by association studies. Mostly important, the above genes are homologous of genes that modulate lifespan in model organisms. We scanned the area in four European sample groups for a total of 1321 centenarians and 1140 younger subjects, who shared with centenarians ethnicity and geographical origin, wi ...[more]

PMID: 19367319

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Project description:BackgroundLarge fluctuations in blood glucose levels greatly impact the health and life span of elderly individuals. This study describes the characteristics of variability in glycemic indices in centenarians with the aim of emphasizing the importance of glycemic variability in elderly people.MethodsWe recruited individuals from Rugao City, Jiangsu Province, China from April 2020 to May 2021. The study cohort included 60 centenarians and 60 first-generation offspring, as well as 20 randomly selected non-cohabitant control individuals aged 60-80 years. A FreeStyle Libre H (hospital version) continuous glucose monitoring (CGM) device (Abbott Ireland UK) was used to measure glycemic variability. The indices measured included the time in target glucose range (TIR), time below target glucose range (TBR), time above target glucose range (TAR), mean amplitude of glycemic excursions (MAGE), mean of daily differences (MODD), coefficient of variation (CV), standard deviation of blood glucose (SDBG), continuous overlapping net glycemic action (CONGA), glucose management indicator (GMI) and estimated glycated hemoglobin (eHbA1c). Logistic regression was used to analyze the association between glycemic variability and longevity.ResultsMean blood glucose (MBG), eHbA1c, GMI, mean fasting plasma glucose (M-FPG) and CONGA were lower in the centenarian group (p all < 0.05). PPGE-2 was higher in the control group than that measured in the centenarian and first-generation offspring groups (p < 0.05). There were no differences between the groups in MAGE, MODD, MAG, or TIR (p > 0.05). The risk of not achieving longevity increased with each one unit increase in MBG by 126% [2.26 (1.05-4.91)], eHbA1c by 67% [1.67 (1.03-2.72)], GMI by 568% [6.68 (1.11-40.30)], M-FPG by 365% [4.65 (1.57-13.75)], M-PPG1h by 98% [1.98 (1.18-3.31)], CONGA1 by 102% [2.02 (1.01-4.06)], Li by 200% [3.00 (1.04-8.61)], and PPGE-2 by 150% [2.50 (1.39-4.50)]. However, the risk of achieving longevity decreased with each unit increase of LBGI by 53% [0.47 (0.28-0.80)], ADRR by 60% [0.40 (0.18-0.86)], and TBR by 11% [0.89 (0.80-0.98)].ConclusionFluctuation in blood glucose levels in centenarians is relatively small. Maintaining an average blood glucose level and keeping blood glucose fluctuations in the normal range is conducive to longevity.

Dataset Information

Human longevity and 11p15.5: a study in 1321 centenarians.

Publications

Human longevity and 11p15.5: a study in 1321 centenarians.

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