Telomeres are essential in maintaining chromosome integrity and in controlling cellular replication. Attrition of telomere length in peripheral blood mononuclear cells (PBMCs) with age is well documented from cross-sectional studies. But the actual in vivo changes in telomere lengths and its relationship with the contributing factors within the individuals with age have not been fully addressed. In the present paper, we report a longitudinal analysis of telomere length in the PBMCs, lymphocytes and monocytes of 216 human subjects aged from 20–90 years assessed at 0-, 5- and 12-year follow-up. For the 5- and 12-year follow-up, telomere length in the PBMCs decreased in 34% and 46%, exhibited no detectable change in 56% and 47% and increased in 10% and 7% of the subjects respectively. The rate of telomere change was distinct for T-cells, B-cells and monocytes for any given subject. Telomerase activity declined with age in the resting T-cells and B-cells and the activated T-cells. Finally, a significant portion of telomere attrition in T-cells with age was explained by a decline in the telomerase activity, decreased naïve cells and the change in physiological conditions such as elevated blood glucose and interleukin (IL)-6 levels. These findings show that changes in the telomere length of the PBMCs with age in vivo occur at different rates in different individuals and cell types and reveal that changes in the telomere length in the T-cells with age is influenced by the telomerase activity, naïve T-cell percentage and changes in health conditions.
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November 28 2014
Age-associated telomere attrition of lymphocytes in vivo is co-ordinated with changes in telomerase activity, composition of lymphocyte subsets and health conditions
Yun Lin;
Yun Lin
*Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, U.S.A.
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Amanda Damjanovic;
Amanda Damjanovic
*Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, U.S.A.
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E. Jeffrey Metter;
E. Jeffrey Metter
†Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224,U.S.A.
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Huy Nguyen;
Huy Nguyen
*Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, U.S.A.
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Thai Truong;
Thai Truong
*Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, U.S.A.
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Kevin Najarro;
Kevin Najarro
*Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, U.S.A.
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Christa Morris;
Christa Morris
‡Flow Cytometry Unit, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, U.S.A.
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Dan L. Longo;
Dan L. Longo
§Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, U.S.A.
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Ming Zhan;
Ming Zhan
║Bioinformatics Unit, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, U.S.A.
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Luigi Ferrucci;
Luigi Ferrucci
†Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224,U.S.A.
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Richard J. Hodes;
Richard J. Hodes
¶National Institute on Aging and Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, U.S.A.
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Nan-ping Weng
*Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, U.S.A.
Correspondence: Dr Nan-ping Weng (email [email protected]).
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Publisher: Portland Press Ltd
Received:
August 06 2014
Accepted:
October 15 2014
Accepted Manuscript online:
October 15 2014
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2015 Biochemical Society
2015
Clin Sci (Lond) (2015) 128 (6): 367–377.
Article history
Received:
August 06 2014
Accepted:
October 15 2014
Accepted Manuscript online:
October 15 2014
Citation
Yun Lin, Amanda Damjanovic, E. Jeffrey Metter, Huy Nguyen, Thai Truong, Kevin Najarro, Christa Morris, Dan L. Longo, Ming Zhan, Luigi Ferrucci, Richard J. Hodes, Nan-ping Weng; Age-associated telomere attrition of lymphocytes in vivo is co-ordinated with changes in telomerase activity, composition of lymphocyte subsets and health conditions. Clin Sci (Lond) 1 March 2015; 128 (6): 367–377. doi: https://doi.org/10.1042/CS20140481
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