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


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

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.

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.

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Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Clinical Chemistry
Dewey Decimal Classification:610 Medicine & health
540 Chemistry
Language:English
Date:June 2016
Deposited On:05 Jul 2016 14:18
Last Modified:19 Aug 2018 03:36
Publisher:Springer
ISSN:0161-9152
OA Status:Closed
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1007/s11357-016-9917-y
PubMed ID:27125385
Project Information:
  • : FunderSNSF
  • : Grant ID4026-028099
  • : Project TitleSwiss study on air pollution and lung diseases in adults (SAPALDIA study)
  • : FunderSNSF
  • : Grant ID324730_135673
  • : Project TitleAir Pollution Exposure Assessment in Eight Swiss Areas
  • : FunderSNSF
  • : Grant ID3200-042532
  • : Project TitleSwiss Study on Air Pollution and Lung Diseases in Adults: Participants'Follow-up and Further Analysis.
  • : FunderSNSF
  • : Grant ID3247-065896
  • : Project TitleThe SAPALDIA II Cohort Study:Impact of environmental and personalrisk factors on the occurrence, course, remission and progressionof respiratory diseases in the Swiss population.
  • : FunderSNSF
  • : Grant ID3100-059302
  • : Project TitleThe SAPALDIA II Cohort Study:Impact of environmental and personalrisk factors on the occurrence, course, remission and progressionof respiratory diseases in the Swiss population.
  • : FunderSNSF
  • : Grant ID3200-052720
  • : Project TitleSwiss Study on Air Pollution and Lung Diseases in Adults: Mortality follow-up extension.

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