title: Age-associated telomere attrition of lymphocytes in vivo is co-ordinated with changes in telomerase activity, composition of lymphocyte subsets and health conditions.
abstract: 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.
authors.affiliation: *Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, U.S.A.
authors.forename: Yun
authors.initials: Y
authors.lastname: Lin
authors.affiliation: *Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, U.S.A.
authors.forename: Amanda
authors.initials: A
authors.lastname: Damjanovic
authors.affiliation: †Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224,U.S.A.
authors.forename: E Jeffrey
authors.initials: EJ
authors.lastname: Metter
authors.affiliation: *Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, U.S.A.
authors.forename: Huy
authors.initials: H
authors.lastname: Nguyen
authors.affiliation: *Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, U.S.A.
authors.forename: Thai
authors.initials: T
authors.lastname: Truong
authors.affiliation: *Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, U.S.A.
authors.forename: Kevin
authors.initials: K
authors.lastname: Najarro
authors.affiliation: ‡Flow Cytometry Unit, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, U.S.A.
authors.forename: Christa
authors.initials: C
authors.lastname: Morris
authors.affiliation: §Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, U.S.A.
authors.forename: Dan L
authors.initials: DL
authors.lastname: Longo
authors.affiliation: ║Bioinformatics Unit, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, U.S.A.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhan
authors.affiliation: †Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224,U.S.A.
authors.forename: Luigi
authors.initials: L
authors.lastname: Ferrucci
authors.affiliation: ¶National Institute on Aging and Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, U.S.A.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Hodes
authors.affiliation: *Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, U.S.A.
authors.forename: Nan-ping
authors.initials: NP
authors.lastname: Weng
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000201:enzymology / Q000502:physiology; D005500:Follow-Up Studies; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D016131:Lymphocyte Subsets / Q000201:enzymology* / Q000276:immunology; D008875:Middle Aged; D009000:Monocytes / Q000502:physiology; D013601:T-Lymphocytes / Q000201:enzymology / Q000502:physiology; D019098:Telomerase / Q000097:blood*; D059505:Telomere Homeostasis / Q000276:immunology* / Q000502:physiology; D055815:Young Adult
chemical_list: D019098:Telomerase