Telomere length in circulating leukocytes is associated with lung function and disease

Eva Albrecht; Elina Sillanpää; Stefan Karrasch; Alexessander Couto Alves; Veryan Codd; Iiris Hovatta; Jessica L. Buxton; Christopher P. Nelson; Linda Broer; Sara Hägg; Massimo Mangino; Gonneke Willemsen; Ida Surakka; Manuel A.R. Ferreira; Najaf Amin; Ben A. Oostra; Heli M. Bäckmand; Markku Peltonen; Seppo Sarna; Taina Rantanen; Sarianna Sipilä; Tellervo Korhonen; Pamela A.F. Madden; Christian Gieger; Rudolf A. Jörres; Joachim Heinrich; Jürgen Behr; Rudolf M. Huber; Annette Peters; Konstantin Strauch; H. Erich Wichmann; Melanie Waldenberger; Alexandra I.F. Blakemore; Eco J.C. De Geus; Dale R. Nyholt; Anjali K. Henders; Päivi L. Piirilä; Aila Rissanen; Patrik K.E. Magnusson; Ana Viñuela; Kirsi H. Pietiläinen; Nicholas G. Martin; Nancy L. Pedersen; Dorret I. Boomsma; Tim D. Spector; Cornelia M. Van Duijn; Jaakko Kaprio; Nilesh J. Samani; Marjo Riitta Jarvelin; Holger Schulz

doi:10.1183/09031936.00046213

Telomere length in circulating leukocytes is associated with lung function and disease

Eva Albrecht, Elina Sillanpää, Stefan Karrasch, Alexessander Couto Alves, Veryan Codd, Iiris Hovatta, Jessica L. Buxton, Christopher P. Nelson, Linda Broer, Sara Hägg, Massimo Mangino, Gonneke Willemsen, Ida Surakka, Manuel A.R. Ferreira, Najaf Amin, Ben A. Oostra, Heli M. Bäckmand, Markku Peltonen, Seppo Sarna, Taina RantanenSarianna Sipilä, Tellervo Korhonen, Pamela A.F. Madden, Christian Gieger, Rudolf A. Jörres, Joachim Heinrich, Jürgen Behr, Rudolf M. Huber, Annette Peters, Konstantin Strauch, H. Erich Wichmann, Melanie Waldenberger, Alexandra I.F. Blakemore, Eco J.C. De Geus, Dale R. Nyholt, Anjali K. Henders, Päivi L. Piirilä, Aila Rissanen, Patrik K.E. Magnusson, Ana Viñuela, Kirsi H. Pietiläinen, Nicholas G. Martin, Nancy L. Pedersen, Dorret I. Boomsma, Tim D. Spector, Cornelia M. Van Duijn, Jaakko Kaprio, Nilesh J. Samani, Marjo Riitta Jarvelin, Holger Schulz

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Abstract

Several clinical studies suggest the involvement of premature ageing processes in chronic obstructive pulmonary disease (COPD). Using an epidemiological approach, we studied whether accelerated ageing indicated by telomere length, a marker of biological age, is associated with COPD and asthma, and whether intrinsic age-related processes contribute to the interindividual variability of lung function. Our meta-analysis of 14 studies included 934 COPD cases with 15 846 controls defined according to the Global Lungs Initiative (GLI) criteria (or 1189 COPD cases according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria), 2834 asthma cases with 28 195 controls, and spirometric parameters (forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC) of 12 595 individuals. Associations with telomere length were tested by linear regression, adjusting for age, sex and smoking status. We observed negative associations between telomere length and asthma (β= -0.0452, p=0.024) as well as COPD (β= -0.0982, p=0.001), with associations being stronger and more significant when using GLI criteria than those of GOLD. In both diseases, effects were stronger in females than males. The investigation of spirometric indices showed positive associations between telomere length and FEV1 (p=1.07×10^-7), FVC (p=2.07×10^-5), and FEV1/FVC (p=5.27×10^-3). The effect was somewhat weaker in apparently healthy subjects than in COPD or asthma patients. Our results provide indirect evidence for the hypothesis that cellular senescence may contribute to the pathogenesis of COPD and asthma, and that lung function may reflect biological ageing primarily due to intrinsic processes, which are likely to be aggravated in lung diseases.

Original language	English
Pages (from-to)	983-992
Number of pages	10
Journal	European Respiratory Journal
Volume	43
Issue number	4
DOIs	https://doi.org/10.1183/09031936.00046213
State	Published - Apr 1 2014

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Albrecht, E., Sillanpää, E., Karrasch, S., Alves, A. C., Codd, V., Hovatta, I., Buxton, J. L., Nelson, C. P., Broer, L., Hägg, S., Mangino, M., Willemsen, G., Surakka, I., Ferreira, M. A. R., Amin, N., Oostra, B. A., Bäckmand, H. M., Peltonen, M., Sarna, S., ... Schulz, H. (2014). Telomere length in circulating leukocytes is associated with lung function and disease. European Respiratory Journal, 43(4), 983-992. https://doi.org/10.1183/09031936.00046213

@article{ac18a3ee031047859016a73d6a802bb0,

title = "Telomere length in circulating leukocytes is associated with lung function and disease",

abstract = "Several clinical studies suggest the involvement of premature ageing processes in chronic obstructive pulmonary disease (COPD). Using an epidemiological approach, we studied whether accelerated ageing indicated by telomere length, a marker of biological age, is associated with COPD and asthma, and whether intrinsic age-related processes contribute to the interindividual variability of lung function. Our meta-analysis of 14 studies included 934 COPD cases with 15 846 controls defined according to the Global Lungs Initiative (GLI) criteria (or 1189 COPD cases according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria), 2834 asthma cases with 28 195 controls, and spirometric parameters (forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC) of 12 595 individuals. Associations with telomere length were tested by linear regression, adjusting for age, sex and smoking status. We observed negative associations between telomere length and asthma (β= -0.0452, p=0.024) as well as COPD (β= -0.0982, p=0.001), with associations being stronger and more significant when using GLI criteria than those of GOLD. In both diseases, effects were stronger in females than males. The investigation of spirometric indices showed positive associations between telomere length and FEV1 (p=1.07×10-7), FVC (p=2.07×10-5), and FEV1/FVC (p=5.27×10-3). The effect was somewhat weaker in apparently healthy subjects than in COPD or asthma patients. Our results provide indirect evidence for the hypothesis that cellular senescence may contribute to the pathogenesis of COPD and asthma, and that lung function may reflect biological ageing primarily due to intrinsic processes, which are likely to be aggravated in lung diseases.",

author = "Eva Albrecht and Elina Sillanp{\"a}{\"a} and Stefan Karrasch and Alves, {Alexessander Couto} and Veryan Codd and Iiris Hovatta and Buxton, {Jessica L.} and Nelson, {Christopher P.} and Linda Broer and Sara H{\"a}gg and Massimo Mangino and Gonneke Willemsen and Ida Surakka and Ferreira, {Manuel A.R.} and Najaf Amin and Oostra, {Ben A.} and B{\"a}ckmand, {Heli M.} and Markku Peltonen and Seppo Sarna and Taina Rantanen and Sarianna Sipil{\"a} and Tellervo Korhonen and Madden, {Pamela A.F.} and Christian Gieger and J{\"o}rres, {Rudolf A.} and Joachim Heinrich and J{\"u}rgen Behr and Huber, {Rudolf M.} and Annette Peters and Konstantin Strauch and Wichmann, {H. Erich} and Melanie Waldenberger and Blakemore, {Alexandra I.F.} and {De Geus}, {Eco J.C.} and Nyholt, {Dale R.} and Henders, {Anjali K.} and Piiril{\"a}, {P{\"a}ivi L.} and Aila Rissanen and Magnusson, {Patrik K.E.} and Ana Vi{\~n}uela and Pietil{\"a}inen, {Kirsi H.} and Martin, {Nicholas G.} and Pedersen, {Nancy L.} and Boomsma, {Dorret I.} and Spector, {Tim D.} and {Van Duijn}, {Cornelia M.} and Jaakko Kaprio and Samani, {Nilesh J.} and Jarvelin, {Marjo Riitta} and Holger Schulz",

year = "2014",

month = apr,

day = "1",

doi = "10.1183/09031936.00046213",

language = "English",

volume = "43",

pages = "983--992",

journal = "European Respiratory Journal",

issn = "0903-1936",

number = "4",

}

Albrecht, E, Sillanpää, E, Karrasch, S, Alves, AC, Codd, V, Hovatta, I, Buxton, JL, Nelson, CP, Broer, L, Hägg, S, Mangino, M, Willemsen, G, Surakka, I, Ferreira, MAR, Amin, N, Oostra, BA, Bäckmand, HM, Peltonen, M, Sarna, S, Rantanen, T, Sipilä, S, Korhonen, T, Madden, PAF, Gieger, C, Jörres, RA, Heinrich, J, Behr, J, Huber, RM, Peters, A, Strauch, K, Wichmann, HE, Waldenberger, M, Blakemore, AIF, De Geus, EJC, Nyholt, DR, Henders, AK, Piirilä, PL, Rissanen, A, Magnusson, PKE, Viñuela, A, Pietiläinen, KH, Martin, NG, Pedersen, NL, Boomsma, DI, Spector, TD, Van Duijn, CM, Kaprio, J, Samani, NJ, Jarvelin, MR & Schulz, H 2014, 'Telomere length in circulating leukocytes is associated with lung function and disease', European Respiratory Journal, vol. 43, no. 4, pp. 983-992. https://doi.org/10.1183/09031936.00046213

TY - JOUR

T1 - Telomere length in circulating leukocytes is associated with lung function and disease

AU - Albrecht, Eva

AU - Sillanpää, Elina

AU - Karrasch, Stefan

AU - Alves, Alexessander Couto

AU - Codd, Veryan

AU - Hovatta, Iiris

AU - Buxton, Jessica L.

AU - Nelson, Christopher P.

AU - Broer, Linda

AU - Hägg, Sara

AU - Mangino, Massimo

AU - Willemsen, Gonneke

AU - Surakka, Ida

AU - Ferreira, Manuel A.R.

AU - Amin, Najaf

AU - Oostra, Ben A.

AU - Bäckmand, Heli M.

AU - Peltonen, Markku

AU - Sarna, Seppo

AU - Rantanen, Taina

AU - Sipilä, Sarianna

AU - Korhonen, Tellervo

AU - Madden, Pamela A.F.

AU - Gieger, Christian

AU - Jörres, Rudolf A.

AU - Heinrich, Joachim

AU - Behr, Jürgen

AU - Huber, Rudolf M.

AU - Peters, Annette

AU - Strauch, Konstantin

AU - Wichmann, H. Erich

AU - Waldenberger, Melanie

AU - Blakemore, Alexandra I.F.

AU - De Geus, Eco J.C.

AU - Nyholt, Dale R.

AU - Henders, Anjali K.

AU - Piirilä, Päivi L.

AU - Rissanen, Aila

AU - Magnusson, Patrik K.E.

AU - Viñuela, Ana

AU - Pietiläinen, Kirsi H.

AU - Martin, Nicholas G.

AU - Pedersen, Nancy L.

AU - Boomsma, Dorret I.

AU - Spector, Tim D.

AU - Van Duijn, Cornelia M.

AU - Kaprio, Jaakko

AU - Samani, Nilesh J.

AU - Jarvelin, Marjo Riitta

AU - Schulz, Holger

PY - 2014/4/1

Y1 - 2014/4/1

N2 - Several clinical studies suggest the involvement of premature ageing processes in chronic obstructive pulmonary disease (COPD). Using an epidemiological approach, we studied whether accelerated ageing indicated by telomere length, a marker of biological age, is associated with COPD and asthma, and whether intrinsic age-related processes contribute to the interindividual variability of lung function. Our meta-analysis of 14 studies included 934 COPD cases with 15 846 controls defined according to the Global Lungs Initiative (GLI) criteria (or 1189 COPD cases according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria), 2834 asthma cases with 28 195 controls, and spirometric parameters (forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC) of 12 595 individuals. Associations with telomere length were tested by linear regression, adjusting for age, sex and smoking status. We observed negative associations between telomere length and asthma (β= -0.0452, p=0.024) as well as COPD (β= -0.0982, p=0.001), with associations being stronger and more significant when using GLI criteria than those of GOLD. In both diseases, effects were stronger in females than males. The investigation of spirometric indices showed positive associations between telomere length and FEV1 (p=1.07×10-7), FVC (p=2.07×10-5), and FEV1/FVC (p=5.27×10-3). The effect was somewhat weaker in apparently healthy subjects than in COPD or asthma patients. Our results provide indirect evidence for the hypothesis that cellular senescence may contribute to the pathogenesis of COPD and asthma, and that lung function may reflect biological ageing primarily due to intrinsic processes, which are likely to be aggravated in lung diseases.

AB - Several clinical studies suggest the involvement of premature ageing processes in chronic obstructive pulmonary disease (COPD). Using an epidemiological approach, we studied whether accelerated ageing indicated by telomere length, a marker of biological age, is associated with COPD and asthma, and whether intrinsic age-related processes contribute to the interindividual variability of lung function. Our meta-analysis of 14 studies included 934 COPD cases with 15 846 controls defined according to the Global Lungs Initiative (GLI) criteria (or 1189 COPD cases according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria), 2834 asthma cases with 28 195 controls, and spirometric parameters (forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC) of 12 595 individuals. Associations with telomere length were tested by linear regression, adjusting for age, sex and smoking status. We observed negative associations between telomere length and asthma (β= -0.0452, p=0.024) as well as COPD (β= -0.0982, p=0.001), with associations being stronger and more significant when using GLI criteria than those of GOLD. In both diseases, effects were stronger in females than males. The investigation of spirometric indices showed positive associations between telomere length and FEV1 (p=1.07×10-7), FVC (p=2.07×10-5), and FEV1/FVC (p=5.27×10-3). The effect was somewhat weaker in apparently healthy subjects than in COPD or asthma patients. Our results provide indirect evidence for the hypothesis that cellular senescence may contribute to the pathogenesis of COPD and asthma, and that lung function may reflect biological ageing primarily due to intrinsic processes, which are likely to be aggravated in lung diseases.

UR - http://www.scopus.com/inward/record.url?scp=84897383442&partnerID=8YFLogxK

U2 - 10.1183/09031936.00046213

DO - 10.1183/09031936.00046213

M3 - Article

C2 - 24311771

AN - SCOPUS:84897383442

SN - 0903-1936

VL - 43

SP - 983

EP - 992

JO - European Respiratory Journal

JF - European Respiratory Journal

IS - 4

ER -

Telomere length in circulating leukocytes is associated with lung function and disease

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