The Individual Blood Cell Telomere Attrition Rate Is Telomere Length Dependent

被引:150
作者
Nordfjall, Katarina [1 ]
Svenson, Ulrika [1 ]
Norrback, Karl-Fredrik [2 ,3 ]
Adolfsson, Rolf [2 ,3 ]
Lenner, Per [4 ]
Roos, Goran [1 ]
机构
[1] Umea Univ, Dept Med Biosci, Umea, Sweden
[2] Umea Univ, Dept Clin Sci, Umea, Sweden
[3] Sunderby Hosp, Psychiat Clin, Lulea, Sweden
[4] Umea Univ, Dept Radiat Sci, Umea, Sweden
基金
瑞典研究理事会;
关键词
CHROMOSOME-SPECIFIC VARIATIONS; HUMANS; RISK; AGE; LYMPHOCYTES; DYSFUNCTION; PROTEINS; PATTERN; MICE;
D O I
10.1371/journal.pgen.1000375
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Age-associated telomere shortening is a well documented feature of peripheral blood cells in human population studies, but it is not known to what extent these data can be transferred to the individual level. Telomere length (TL) in two blood samples taken at,10 years interval from 959 individuals was investigated using real-time PCR. TL was also measured in 13 families from a multigenerational cohort. As expected, we found an age-related decline in TL over time (r = -0.164, P < 0.001, n = 959). However, approximately one-third of the individuals exhibited a stable or increased TL over a decade. The individual telomere attrition rate was inversely correlated with initial TL at a highly significant level (r = -0.752, P < 0.001), indicating that the attrition rate was most pronounced in individuals with long telomeres at baseline. In accordance, the age-associated telomere attrition rate was more prominent in families with members displaying longer telomeres at a young age (r = -0.691, P < 0.001). Abnormal blood TL has been reported at diagnosis of various malignancies, but in the present study there was no association between individual telomere attrition rate or prediagnostic TL and later tumor development. The collected data strongly suggest a TL maintenance mechanism acting in vivo, providing protection of short telomeres as previously demonstrated in vitro. Our findings might challenge the hypothesis that individual TL can predict possible life span or later tumor development.
引用
收藏
页数:6
相关论文
共 36 条
[1]   Targeting assay to study the cis functions of human telomeric proteins:: Evidence for inhibition of telomerase by TRF1 and for activation of telomere degradation by TRF2 [J].
Ancelin, K ;
Brunori, M ;
Bauwens, S ;
Koering, CE ;
Brun, C ;
Ricoul, M ;
Pommier, JP ;
Sabatier, L ;
Gilson, E .
MOLECULAR AND CELLULAR BIOLOGY, 2002, 22 (10) :3474-3487
[2]  
AVIV A, 2008, AM J EPIDEM IN PRESS
[3]   Is telomere length in peripheral blood lymphocytes correlated with cancer susceptibility or radiosensitivity? [J].
Barwell, J. ;
Pangon, L. ;
Georgiou, A. ;
Docherty, Z. ;
Kesterton, I. ;
Ball, J. ;
Camplejohn, R. ;
Berg, J. ;
Aviv, A. ;
Gardner, J. ;
Kato, B. S. ;
Carter, N. ;
Paximadas, D. ;
Spector, T. D. ;
Hodgson, S. .
BRITISH JOURNAL OF CANCER, 2007, 97 (12) :1696-1700
[4]   Telomere length and cardiovascular risk factors in a middle-aged population free of overt cardiovascular disease [J].
Bekaert, Sofie ;
De Meyer, Tim ;
Rietzschel, Ernst R. ;
De Buyzere, Marc L. ;
De Bacquer, Dirk ;
Langlois, Michel ;
Segers, Patrick ;
Cooman, Luc ;
Van Damme, Piet ;
Cassiman, Peter ;
Van Criekinge, Wim ;
Verdonck, Pascal ;
De Backer, Guy G. ;
Gillebert, Thierry C. ;
Van Oostveldt, Patrick .
AGING CELL, 2007, 6 (05) :639-647
[5]   The epigenetic regulation of mammalian telomeres [J].
Blasco, Maria A. .
NATURE REVIEWS GENETICS, 2007, 8 (04) :299-309
[6]   Telomere measurement by quantitative PCR [J].
Cawthon, RM .
NUCLEIC ACIDS RESEARCH, 2002, 30 (10) :e47
[7]   The association between physical activity in leisure time and leukocyte telomere length [J].
Cherkas, Lynn F. ;
Hunkin, Janice L. ;
Kato, Bernet S. ;
Richards, J. Brent ;
Gardner, Jeffrey P. ;
Surdulescu, Gabriela L. ;
Kimura, Masayuki ;
Lu, Xiaobin ;
Spector, Tim D. ;
Aviv, Abraham .
ARCHIVES OF INTERNAL MEDICINE, 2008, 168 (02) :154-158
[8]   The rate of telomere sequence loss in human leukocytes varies with age [J].
Frenck, RW ;
Blackburn, EH ;
Shannon, KM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (10) :5607-5610
[9]   Rise in insulin resistance is associated with escalated telomere attrition [J].
Gardner, JP ;
Li, SX ;
Srinivasan, SR ;
Chen, W ;
Kimura, M ;
Lu, XB ;
Berenson, GS ;
Aviv, A .
CIRCULATION, 2005, 111 (17) :2171-2177
[10]   Multilevel modelling of medical data [J].
Goldstein, H ;
Browne, W ;
Rasbash, J .
STATISTICS IN MEDICINE, 2002, 21 (21) :3291-3315