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Common SIRT1 variants modify the effect of abdominal adipose tissue on aging-related lung function decline

Curjuric, Ivan and Imboden, Medea and Bridevaux, Pierre-Olivier and Gerbase, Margaret W. and Haun, Margot and Keidel, Dirk and Kumar, Ashish and Pons, Marco and Rochat, Thierry and Schikowski, Tamara and Schindler, Christian and von Eckardstein, Arnold and Kronenberg, Florian and Probst-Hensch, Nicole M.. (2016) Common SIRT1 variants modify the effect of abdominal adipose tissue on aging-related lung function decline. Age, 38 (3). p. 52.

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Official URL: http://edoc.unibas.ch/43239/

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Abstract

Lung function is an independent predictor of mortality and serves as an aging marker in never smokers. The protein sirtuin-1 of gene SIRT1 has profound anti-inflammatory effects and regulates metabolic pathways. Its suggested longevity effects on lower organisms remain poorly studied in humans. In 1132 never smokers of the population-based SAPALDIA cohort, we investigated associations between single nucleotide polymorphisms (SNPs; rs730821, rs10997868, rs10823116) of SIRT1 and aging-related lung function decline over 11 years in terms of change in forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, and forced expiratory flow between 25 and 75 % of FVC (FEF25-75) using multiple linear regression models. Interactions between the SIRT1 SNPs and adiposity parameters (body mass index (BMI), its change and weight gain) were tested by including multiplicative interaction terms into the models. SIRT1 polymorphisms exhibited no main effects, but modified the association between obesity measures and FEV1/FVC and FEF25-75 decline (p = 0.009-0.046). Per risk allele, FEV1/FVC decline was accelerated up to -0.5 % (95 % CI -1.0 to 0 %) and -0.7 % (-1.3 to -0.2 %) over interquartile range increases in BMI (2.4 kg/m(2)) or weight (6.5 kg), respectively. For FEF25-75 decline, corresponding estimates were -57 mL/s (-117 to 4 mL/s) and -76 mL/s (-1429 to -9 mL/s). Interactions were not present in participants with genetically lowered C-reactive protein concentrations. Genetic variation in SIRT1 might therefore affect lung function and human longevity by modifying subclinical inflammation arising from abdominal adipose tissue.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
UniBasel Contributors:Curjuric, Ivan
Item Type:Article, refereed
Publisher:Springer
ISSN:0161-9152
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:30 Jun 2016 11:04
Deposited On:28 Jun 2016 08:02

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