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

K. H. Pietilainen; N. G. Martin; N. L. Pedersen; D. I. Boomsma; T. D. Spector; C. M. van Duijn; J. Kaprio; N. J. Samani; M.-R. Jarvelin; H. Schulz; J. Behr; R. M. Huber; A. Peters; K. Strauch; H. E. Wichmann; M. Waldenberger; A. I. F. Blakemore; E. J. C. de Geus; D. R. Nyholt; A. K. Henders; P. L. Piirila; A. Rissanen; P. K. E. Magnusson; A. Vinuela; Eva Albrecht; Elina Sillanpaa; Stefan Karrasch; Alexessander Alves; Veryan Codd; Iiris Hovatta; Jessica L. Buxton; Christopher P. Nelson; Linda Broer; Sara Hagg; Massimo Mangino; Gonneke Willemsen; Ida Surakka; Manuel A.R. Ferreira; Najaf Amin; Ben A. Oostra; H. M. Backmand; M. Peltonen; S. Sarna; T. Rantanen; S. Sipila; T. Korhonen; P. A. F. Madden; C. Gieger; R. A. Jorres; J. Heinrich

doi:10.1183/09031936.00046213

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

K. H. Pietilainen, N. G. Martin, N. L. Pedersen, D. I. Boomsma, T. D. Spector, C. M. van Duijn, J. Kaprio, N. J. Samani, M.-R. Jarvelin, H. Schulz, J. Behr, R. M. Huber, A. Peters, K. Strauch, H. E. Wichmann, M. Waldenberger, A. I. F. Blakemore, E. J. C. de Geus, D. R. Nyholt, A. K. HendersP. L. Piirila, A. Rissanen, P. K. E. Magnusson, A. Vinuela, Eva Albrecht, Elina Sillanpaa, Stefan Karrasch, Alexessander Alves, Veryan Codd, Iiris Hovatta, Jessica L. Buxton, Christopher P. Nelson, Linda Broer, Sara Hagg, Massimo Mangino, Gonneke Willemsen, Ida Surakka, Manuel A.R. Ferreira, Najaf Amin, Ben A. Oostra, H. M. Backmand, M. Peltonen, S. Sarna, T. Rantanen, S. Sipila, T. Korhonen, P. A. F. Madden, C. Gieger, R. A. Jorres, J. Heinrich

Research output: Contribution to journal › Article › peer-review

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 ([beta]= -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
Journal	European Respiratory Journal
Volume	43
Issue number	4
DOIs	https://doi.org/10.1183/09031936.00046213
Publication status	Published - 1 Apr 2014

Keywords

Biological sciences

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10.1183/09031936.00046213

https://doi.org/10.1183/09031936.00046213

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Pietilainen, K. H., Martin, N. G., Pedersen, N. L., Boomsma, D. I., Spector, T. D., van Duijn, C. M., Kaprio, J., Samani, N. J., Jarvelin, M.-R., Schulz, H., Behr, J., Huber, R. M., Peters, A., Strauch, K., Wichmann, H. E., Waldenberger, M., Blakemore, A. I. F., de Geus, E. J. C., Nyholt, D. R., ... Heinrich, J. (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

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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 ([beta]= -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.",

keywords = "Biological sciences",

author = "Pietilainen, \{K. H.\} and Martin, \{N. G.\} and Pedersen, \{N. L.\} and Boomsma, \{D. I.\} and Spector, \{T. D.\} and \{van Duijn\}, \{C. M.\} and J. Kaprio and Samani, \{N. J.\} and M.-R. Jarvelin and H. Schulz and J. Behr and Huber, \{R. M.\} and A. Peters and K. Strauch and Wichmann, \{H. E.\} and M. Waldenberger and Blakemore, \{A. I. F.\} and \{de Geus\}, \{E. J. C.\} and Nyholt, \{D. R.\} and Henders, \{A. K.\} and Piirila, \{P. L.\} and A. Rissanen and Magnusson, \{P. K. E.\} and A. Vinuela and Eva Albrecht and Elina Sillanpaa and Stefan Karrasch and Alexessander Alves and Veryan Codd and Iiris Hovatta and Buxton, \{Jessica L.\} and Nelson, \{Christopher P.\} and Linda Broer and Sara Hagg and Massimo Mangino and Gonneke Willemsen and Ida Surakka and Ferreira, \{Manuel A.R.\} and Najaf Amin and Oostra, \{Ben A.\} and Backmand, \{H. M.\} and M. Peltonen and S. Sarna and T. Rantanen and S. Sipila and T. Korhonen and Madden, \{P. A. F.\} and C. Gieger and Jorres, \{R. A.\} and J. Heinrich",

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",

publisher = "European Respiratory Society",

number = "4",

}

Pietilainen, KH, Martin, NG, Pedersen, NL, Boomsma, DI, Spector, TD, van Duijn, CM, Kaprio, J, Samani, NJ, Jarvelin, M-R, Schulz, H, Behr, J, Huber, RM, Peters, A, Strauch, K, Wichmann, HE, Waldenberger, M, Blakemore, AIF, de Geus, EJC, Nyholt, DR, Henders, AK, Piirila, PL, Rissanen, A, Magnusson, PKE, Vinuela, A, Albrecht, E, Sillanpaa, E, Karrasch, S, Alves, A, Codd, V, Hovatta, I, Buxton, JL, Nelson, CP, Broer, L, Hagg, S, Mangino, M, Willemsen, G, Surakka, I, Ferreira, MAR, Amin, N, Oostra, BA, Backmand, HM, Peltonen, M, Sarna, S, Rantanen, T, Sipila, S, Korhonen, T, Madden, PAF, Gieger, C, Jorres, RA & Heinrich, J 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 - Pietilainen, K. H.

AU - Martin, N. G.

AU - Pedersen, N. L.

AU - Boomsma, D. I.

AU - Spector, T. D.

AU - van Duijn, C. M.

AU - Kaprio, J.

AU - Samani, N. J.

AU - Jarvelin, M.-R.

AU - Schulz, H.

AU - Behr, J.

AU - Huber, R. M.

AU - Peters, A.

AU - Strauch, K.

AU - Wichmann, H. E.

AU - Waldenberger, M.

AU - Blakemore, A. I. F.

AU - de Geus, E. J. C.

AU - Nyholt, D. R.

AU - Henders, A. K.

AU - Piirila, P. L.

AU - Rissanen, A.

AU - Magnusson, P. K. E.

AU - Vinuela, A.

AU - Albrecht, Eva

AU - Sillanpaa, Elina

AU - Karrasch, Stefan

AU - Alves, Alexessander

AU - Codd, Veryan

AU - Hovatta, Iiris

AU - Buxton, Jessica L.

AU - Nelson, Christopher P.

AU - Broer, Linda

AU - Hagg, Sara

AU - Mangino, Massimo

AU - Willemsen, Gonneke

AU - Surakka, Ida

AU - Ferreira, Manuel A.R.

AU - Amin, Najaf

AU - Oostra, Ben A.

AU - Backmand, H. M.

AU - Peltonen, M.

AU - Sarna, S.

AU - Rantanen, T.

AU - Sipila, S.

AU - Korhonen, T.

AU - Madden, P. A. F.

AU - Gieger, C.

AU - Jorres, R. A.

AU - Heinrich, J.

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 ([beta]= -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 ([beta]= -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.

KW - Biological sciences

UR - https://www.ncbi.nlm.nih.gov/pubmed/24311771

U2 - 10.1183/09031936.00046213

DO - 10.1183/09031936.00046213

M3 - Article

C2 - 24311771

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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