AGE

, 38:52 | Cite as

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

  • Ivan Curjuric
  • Medea Imboden
  • Pierre-Olivier Bridevaux
  • Margaret W. Gerbase
  • Margot Haun
  • Dirk Keidel
  • Ashish Kumar
  • Marco Pons
  • Thierry Rochat
  • Tamara Schikowski
  • Christian Schindler
  • Arnold von Eckardstein
  • Florian Kronenberg
  • Nicole M. Probst-Hensch
Article

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/m2) 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.

Keywords

Sirtuin-1 Lung Metabolism Inflammation Cohort study Population-based 

Notes

Acknowledgments

The authors acknowledge the work of the whole SAPALDIA team: Study directorate: NM Probst-Hensch (PI; e/g); T Rochat (p), C Schindler (s), N Künzli (e/exp), JM Gaspoz (c); the scientific team: JC Barthélémy (c), W Berger (g), R Bettschart (p), A Bircher (a), C Brombach (n), PO Bridevaux (p), L Burdet (p), Felber Dietrich D (e), M Frey (p), U Frey (pd), MW Gerbase (p), D Gold (e), E de Groot (c), W Karrer (p), F Kronenberg (g), B Martin (pa), A Mehta (e), D Miedinger (o), M Pons (p), F Roche (c), T Rothe (p), P Schmid-Grendelmeyer (a), D Stolz (p), A Schmidt-Trucksäss (pa), J Schwartz (e), A Turk (p), A von Eckardstein (cc), E Zemp Stutz (e); and the scientific team at coordinating centers: M Adam (e), I Aguilera (exp), S Brunner (s), D Carballo (c), S Caviezel (pa), I Curjuric (e), A Di Pascale (s), J Dratva (e), R Ducret (s), E Dupuis Lozeron (s), M Eeftens (exp), I Eze (e), E Fischer (g), M Foraster (e), M Germond (s), L Grize (s), S Hansen (e), A Hensel (s), M Imboden (g), A Ineichen (exp), A Jeong (g), D Keidel (s), A Kumar (g), N Maire (s), A Mehta (e), R Meier (exp), E Schaffner (s), T Schikowski (e), M Tsai (exp).

The study could not have been done without the help of the study participants, technical and administrative support, and the medical teams and field workers at the local study sites. Local fieldworkers: Aarau: S Brun, G Giger, M Sperisen, M Stahel, Basel: C Bürli, C Dahler, N Oertli, I Harreh, F Karrer, G Novicic, N Wyttenbacher, Davos: A Saner, P Senn, R Winzeler, Geneva: F Bonfils, B Blicharz, C Landolt, J Rochat, Lugano: S Boccia, E Gehrig, MT Mandia, G Solari, B Viscardi, Montana: AP Bieri, C Darioly, M Maire, Payerne: F Ding, P Danieli A Vonnez, Wald: D Bodmer, E Hochstrasser, R Kunz, C Meier, J Rakic, U Schafroth, and A Walder; administrative staff: N Bauer Ott, C Gabriel, and R Gutknecht.

(a) corresponds to allergology, (c) cardiology, (cc) clinical chemistry, (e) epidemiology, (exp) exposure, (g) genetic and molecular biology, (m) meteorology, (n) nutrition, (o) occupational health, (p) pneumology, (pa) physical activity, (pd) pediatrics, (s) statistics.

Compliance with ethical standards

All study participants gave written informed consent, and the study was approved by the Swiss Academy of Medical Sciences as well as the respective regional ethics committees.

Funding

This work was supported by the Swiss National Science Foundation (grant nos. 33CS30-148470/1, 33CSCO-134276/1, 33CSCO-108796, 324730_135673, 3247BO-104283, 3247BO-104288, 3247BO-104284, 3247-065896, 3100-059302, 3200-052720, 3200-042532, 4026-028099, PMPDP3_129021/1, PMPDP3_141671/1); the Federal Office for the Environment; the Federal Office of Public Health; the Federal Office of Roads and Transport; the canton’s government of Aargau, Basel-Stadt, Basel-Land, Geneva, Luzern, Ticino, Valais, and Zürich; the Swiss Lung League; the canton’s Lung League of Basel Stadt/ Basel Landschaft, Geneva, Ticino, Valais, Graubünden, and Zurich; Stiftung ehemals Bündner Heilstätten; SUVA; Freiwillige Akademische Gesellschaft; UBS Wealth Foundation; Talecris Biotherapeutics GmbH; Abbott Diagnostics; European Commission 018996 (GABRIEL), and Wellcome Trust WT 084703MA.

Supplementary material

11357_2016_9917_MOESM1_ESM.docx (31 kb)
ESM 1(DOCX 30.7 kb)
11357_2016_9917_MOESM2_ESM.docx (66 kb)
ESM 2(DOCX 65.8 kb)

References

  1. Ackermann-Liebrich U et al. (2005) Follow-up of the Swiss Cohort Study on Air Pollution and Lung Diseases in Adults (SAPALDIA 2) 1991–2003: methods and characterization of participants. Soz Praventivmed 50:245–263CrossRefPubMedGoogle Scholar
  2. Ahmadi-Abhari S, Kaptoge S, Luben RN, Wareham NJ, Khaw KT (2014) Longitudinal association of C-reactive protein and lung function over 13 years: The EPIC-Norfolk study. Am J Epidemiol 179:48–56. doi:10.1093/aje/kwt208 CrossRefPubMedGoogle Scholar
  3. Albrecht E et al. (2014) Telomere length in circulating leukocytes is associated with lung function and disease. Eur Respir J 43:983–992. doi:10.1183/09031936.00046213 CrossRefPubMedGoogle Scholar
  4. American Thoracic Society (1987) Standardization of spirometry—1987 update. Statement of the American Thoracic Society. Am Rev Respir Dis 136:1285–1298Google Scholar
  5. Berg AH, Scherer PE (2005) Adipose tissue, inflammation, and cardiovascular disease. Circ Res 96:939–949. doi:10.1161/01.RES.0000163635.62927.34 CrossRefPubMedGoogle Scholar
  6. Bigaard J, Frederiksen K, Tjonneland A, Thomsen BL, Overvad K, Heitmann BL, TI Sorensen (2005) Waist circumference and body composition in relation to all-cause mortality in middle-aged men and women. Int J Obes 29:778–784 doi:10.1038/sj.ijo.0802976.
  7. Brandli O et al. (2000) Re-estimated equations for 5th percentiles of lung function variables. Thorax 55:173–174CrossRefPubMedGoogle Scholar
  8. Burgel PR et al. (2011) Update on the roles of distal airways in COPD. Eur Respir Rev 20:7–22. doi:10.1183/09059180.10010610 CrossRefPubMedGoogle Scholar
  9. Burnett C et al. (2011) Absence of effects of Sir2 overexpression on lifespan in C. elegans and Drosophila. Nature 477:482–485. doi:10.1038/nature10296 CrossRefPubMedPubMedCentralGoogle Scholar
  10. Burney PG, Hooper R (2011) Forced vital capacity, airway obstruction and survival in a general population sample from the USA. Thorax 66:49–54. doi:10.1136/thx.2010.147041 CrossRefPubMedGoogle Scholar
  11. Calabro P et al. (2009) Adipose tissue-mediated inflammation: the missing link between obesity and cardiovascular disease? Intern Emerg Med 4:25–34. doi:10.1007/s11739-008-0207-2 CrossRefPubMedGoogle Scholar
  12. Chong ZZ, Shang YC, Wang S, Maiese K (2012) SIRT1: new avenues of discovery for disorders of oxidative stress. Expert Opin Ther Targets 16:167–178. doi:10.1517/14728222.2012.648926 CrossRefPubMedPubMedCentralGoogle Scholar
  13. Figarska SM, Vonk JM, Boezen HM (2013) SIRT1 polymorphism, long-term survival and glucose tolerance in the general population. PLoS One 8:e58636. doi:10.1371/journal.pone.0058636 CrossRefPubMedPubMedCentralGoogle Scholar
  14. Flachsbart F, Croucher PJ, Nikolaus S, Hampe J, Cordes C, Schreiber S, Nebel A (2006) Sirtuin 1 (SIRT1) sequence variation is not associated with exceptional human longevity. Exp Gerontol 41:98–102. doi:10.1016/j.exger.2005.09.008 CrossRefPubMedGoogle Scholar
  15. Franceschi C, Bonafe M, Valensin S, Olivieri F, De Luca M, Ottaviani E, De Benedictis G (2000) Inflamm-aging: an evolutionary perspective on immunosenescence. Ann N Y Acad Sci 908:244–254CrossRefPubMedGoogle Scholar
  16. Goyal A, Nimmakayala KR, Zonszein J (2014) Is there a paradox in obesity? Cardiol Rev 22:163–170. doi:10.1097/CRD.0000000000000004 CrossRefPubMedPubMedCentralGoogle Scholar
  17. GTEx Consortium, Ardlie KGDD, Segrè AV, Sullivan TJ, Young TR, Gelfand ET, et al. (2015) Human genomics. The Genotype-Tissue Expression (GTEx) pilot analysis: multitissue gene regulation in humans. Science 348:648–660. doi:10.1126/science.1262110 CrossRefPubMedCentralGoogle Scholar
  18. Guarente L (2011) Franklin H. Epstein lecture: sirtuins, aging, and medicine. N Engl J Med 364:2235–2244. doi:10.1056/NEJMra1100831 CrossRefPubMedGoogle Scholar
  19. Hamid Q (2012) Pathogenesis of small airways in asthma. Respiration 84:4–11. doi:10.1159/000339550 CrossRefPubMedGoogle Scholar
  20. Herranz D, Munoz-Martin M, Canamero M, Mulero F, Martinez-Pastor B, Fernandez-Capetillo O, Serrano M (2010) Sirt1 improves healthy ageing and protects from metabolic syndrome-associated cancer. Nat Commun 1:3. doi:10.1038/ncomms1001 CrossRefPubMedPubMedCentralGoogle Scholar
  21. Herranz D, Serrano M (2010) SIRT1: recent lessons from mouse models. Nat Rev Cancer 10:819–823. doi:10.1038/nrc2962 CrossRefPubMedPubMedCentralGoogle Scholar
  22. Hwang JW, Chung S, Sundar IK, Yao H, Arunachalam G, McBurney MW, Rahman I (2010) Cigarette smoke-induced autophagy is regulated by SIRT1-PARP-1-dependent mechanism: implication in pathogenesis of COPD. Arch Biochem Biophys 500:203–209. doi:10.1016/j.abb.2010.05.013 CrossRefPubMedPubMedCentralGoogle Scholar
  23. Imboden M et al. (2012) Genome-wide association study of lung function decline in adults with and without asthma. J Allergy Clinical Immunol 129:1218–1228. doi:10.1016/j.jaci.2012.01.074 CrossRefGoogle Scholar
  24. International HapMap Consortium (2005) A haplotype map of the human genome. Nature 437:1299–1320. doi:10.1038/nature04226
  25. Kedenko L et al. (2014) Genetic polymorphisms at SIRT1 and FOXO1 are associated with carotid atherosclerosis in the SAPHIR cohort. BMC Med Genet 15:112. doi:10.1186/s12881-014-0112-7 CrossRefPubMedPubMedCentralGoogle Scholar
  26. Kennedy BK et al. (1997) Redistribution of silencing proteins from telomeres to the nucleolus is associated with extension of life span in S. cerevisiae. Cell 89:381–391CrossRefPubMedGoogle Scholar
  27. Kettunen T et al. (2011) Polymorphism in the C-reactive protein (CRP) gene affects CRP levels in plasma and one early marker of atherosclerosis in men: The Health 2000 Survey. Scand J Clin Lab Invest 71:353–361. doi:10.3109/00,365,513.2011.568123 CrossRefPubMedGoogle Scholar
  28. Knuiman MW, James AL, Divitini ML, Ryan G, Bartholomew HC, Musk AW (1999) Lung function, respiratory symptoms, and mortality: results from the Busselton Health Study. Ann Epidemiol 9:297–306CrossRefPubMedGoogle Scholar
  29. Kuningas M, Putters M, Westendorp RG, Slagboom PE, van Heemst D (2007) SIRT1 gene, age-related diseases, and mortality: the Leiden 85-plus study. J Gerontol A Biol Sci Med Sci 62:960–965CrossRefPubMedGoogle Scholar
  30. Leone N et al. (2009) Lung function impairment and metabolic syndrome: the critical role of abdominal obesity. Am J Respir Crit Care Med 179:509–516. doi:10.1164/rccm.200807-1195OC CrossRefPubMedGoogle Scholar
  31. Lopez-Otin C, Blasco MA, Partridge L, Serrano M, Kroemer G (2013) The hallmarks of aging. Cell 153:1194–1217. doi:10.1016/j.cell.2013.05.039 CrossRefPubMedPubMedCentralGoogle Scholar
  32. Mannino DM, Reichert MM, Davis KJ (2006) Lung function decline and outcomes in an adult population. Am J Respir Crit Care Med 173:985–990. doi:10.1164/rccm.200508-1344OC CrossRefPubMedGoogle Scholar
  33. Moffatt MF et al. (2010) A large-scale, consortium-based genomewide association study of asthma. N Engl J Med 363:1211–1221. doi:10.1056/NEJMoa0906312 CrossRefPubMedPubMedCentralGoogle Scholar
  34. Ochs-Balcom HM et al. (2006) Pulmonary function and abdominal adiposity in the general population. Chest 129:853–862. doi:10.1378/chest.129.4.853 CrossRefPubMedGoogle Scholar
  35. Picard F, Guarente L (2005) Molecular links between aging and adipose tissue. Int J Obes 29(Suppl 1):S36–S39. doi:10.1038/sj.ijo.0802912 CrossRefGoogle Scholar
  36. Quanjer PH et al. (2012) Multi-ethnic reference values for spirometry for the 3–95-yr age range: the global lung function 2012 equations. Eur Respir J 40:1324–1343. doi:10.1183/09,031,936.00080312 CrossRefPubMedPubMedCentralGoogle Scholar
  37. Radak Z et al. (2013) Redox-regulating sirtuins in aging, caloric restriction, and exercise. Free Radic Biol Med 58:87–97. doi:10.1016/j.freeradbiomed.2013.01.004 CrossRefPubMedGoogle Scholar
  38. Reis JP, Macera CA, Araneta MR, Lindsay SP, Marshall SJ, Wingard DL (2009) Comparison of overall obesity and body fat distribution in predicting risk of mortality. Obesity 17:1232–1239. doi:10.1038/oby.2008.664 PubMedGoogle Scholar
  39. Rizki G et al. (2011) The evolutionarily conserved longevity determinants HCF-1 and SIR-2.1/SIRT1 collaborate to regulate DAF-16/FOXO. PLoS Genet 7:e1002235. doi:10.1371/journal.pgen.1002235 CrossRefPubMedPubMedCentralGoogle Scholar
  40. Ryan G, Knuiman MW, Divitini ML, James A, Musk AW, Bartholomew HC (1999) Decline in lung function and mortality: the Busselton Health Study. J Epidemiol Community Health 53:230–234CrossRefPubMedPubMedCentralGoogle Scholar
  41. Sabia S, Shipley M, Elbaz A, Marmot M, Kivimaki M, Kauffmann F, Singh-Manoux A (2010) Why does lung function predict mortality? Results from the Whitehall II Cohort Study. Am J Epidemiol 172:1415–1423. doi:10.1093/aje/kwq294 CrossRefPubMedPubMedCentralGoogle Scholar
  42. Schunemann HJ, Dorn J, Grant BJ, W Winkelstein. Jr., Trevisan M (2000) Pulmonary function is a long-term predictor of mortality in the general population: 29-year follow-up of the Buffalo Health Study. Chest 118:656–664.Google Scholar
  43. Shaaban R et al. (2006) Change in C-reactive protein levels and FEV1 decline: a longitudinal population-based study. Respir Med 100:2112–2120. doi:10.1016/j.rmed.2006.03.027 CrossRefPubMedGoogle Scholar
  44. Siedlinski M, Boer JM, Smit HA, Postma DS, Boezen HM (2012) Dietary factors and lung function in the general population: wine and resveratrol intake. Eur Respir J 39:385–391. doi:10.1183/09031936.00184110 CrossRefPubMedGoogle Scholar
  45. Tockman MS et al. (1995) Rapid decline in FEV1. A new risk factor for coronary heart disease mortality. Am J Respir Crit Care Med 151:390–398. doi:10.1164/ajrccm.151.2.7842197 CrossRefPubMedGoogle Scholar
  46. Viswanathan M, Guarente L (2011) Regulation of Caenorhabditis elegans lifespan by sir-2.1 transgenes. Nature 477:E1–E2. doi:10.1038/nature10440 CrossRefPubMedGoogle Scholar
  47. Ward LD, Kellis M (2012) HaploReg: a resource for exploring chromatin states, conservation, and regulatory motif alterations within sets of genetically linked variants. Nucleic Acids Res 40:D930–D934. doi:10.1093/nar/gkr917 CrossRefPubMedGoogle Scholar
  48. Wehrmeister FC, Menezes AM, Muniz LC, Martinez-Mesa J, Domingues MR, Horta BL (2012) Waist circumference and pulmonary function: a systematic review and meta-analysis. Syst Rev 1:55. doi:10.1186/2046-4053-1-55 CrossRefPubMedPubMedCentralGoogle Scholar
  49. Yao H et al. (2013) SIRT1 redresses the imbalance of tissue inhibitor of matrix metalloproteinase-1 and matrix metalloproteinase-9 in the development of mouse emphysema and human COPD. Am J Phys Lung Cell Mol Phys 305:L615–L624. doi:10.1152/ajplung.00249.2012 Google Scholar
  50. Yao H et al. (2014) SIRT1 protects against cigarette smoke-induced lung oxidative stress via a FOXO3-dependent mechanism. Am J Phys Lung Cell Mol Phys 306:L816–L828. doi:10.1152/ajplung.00323.2013 Google Scholar
  51. Zhang C, Rexrode KM, van Dam RM, Li TY, Hu FB (2008) Abdominal obesity and the risk of all-cause, cardiovascular, and cancer mortality: sixteen years of follow-up in US women. Circulation 117:1658–1667. doi:10.1161/CIRCULATIONAHA.107.739714 CrossRefPubMedGoogle Scholar
  52. Zillikens MC et al. (2009a) SIRT1 genetic variation is related to BMI and risk of obesity. Diabetes 58:2828–2834. doi:10.2337/db09-0536 CrossRefPubMedPubMedCentralGoogle Scholar
  53. Zillikens MC et al. (2009b) SIRT1 genetic variation and mortality in type 2 diabetes: interaction with smoking and dietary niacin. Free Radic Biol Med 46:836–841. doi:10.1016/j.freeradbiomed.2008.12.022 CrossRefPubMedGoogle Scholar

Copyright information

© American Aging Association 2016

Authors and Affiliations

  • Ivan Curjuric
    • 1
    • 2
  • Medea Imboden
    • 1
    • 2
  • Pierre-Olivier Bridevaux
    • 3
  • Margaret W. Gerbase
    • 3
  • Margot Haun
    • 4
  • Dirk Keidel
    • 1
    • 2
  • Ashish Kumar
    • 1
    • 2
    • 5
  • Marco Pons
    • 6
  • Thierry Rochat
    • 3
  • Tamara Schikowski
    • 1
    • 2
    • 7
  • Christian Schindler
    • 1
    • 2
  • Arnold von Eckardstein
    • 8
  • Florian Kronenberg
    • 4
  • Nicole M. Probst-Hensch
    • 1
    • 2
  1. 1.Department of Epidemiology and Public HealthSwiss Tropical and Public Health InstituteBaselSwitzerland
  2. 2.University of BaselBaselSwitzerland
  3. 3.Division of Pulmonary MedicineUniversity HospitalsGenevaSwitzerland
  4. 4.Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical PharmacologyMedical University of InnsbruckInnsbruckAustria
  5. 5.Institute of Environmental MedicineKarolinska InstitutetStockholmSweden
  6. 6.Division of Pulmonary MedicineRegional Hospital of LuganoLuganoSwitzerland
  7. 7.Leibniz Research Institute for Environmental Medicine (IUF)DüsseldorfGermany
  8. 8.Institute for Clinical ChemistryUniversity Hospital ZürichZürichSwitzerland

Personalised recommendations