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* Laboratory of Immunology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224;
Institute for Behavioral Medicine Research, College of Medicine, The Ohio State University, Columbus, OH 43210;
Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210;
Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, Columbus, OH 43210;
¶ Department of Psychiatry, The Ohio State University, Columbus, OH 43210; and
|| Department of Neurology, The Ohio State University, Columbus, OH 43210
Caregivers of Alzheimer’s disease patients endure chronic stress associated with a decline of immune function. To assess the psychological and immunological changes of caregivers, we compared depressive symptoms, PBMC composition, in vitro activation-induced proliferation and cytokine production, and telomere length and telomerase activity of 82 individuals (41 caregivers and 41 age- and gender-matched controls). We found depressive symptoms were significantly higher in caregivers than in controls (p < 0.001). Correspondingly, caregivers had significantly lower T cell proliferation but higher production of immune-regulatory cytokines (TNF-
and IL-10) than controls in response to stimulation in vitro. We examined the impact of these changes on cellular replicative lifespan and found that caregivers had significantly shorter telomere lengths in PBMC than controls (6.2 and 6.4 kb, respectively, p < 0.05) with similar shortening in isolated T cells and monocytes and that this telomere attrition in caregivers was not due to an increase of shorter telomere possessing T cell subsets in PBMC. Finally, we showed that basal telomerase activity in PBMC and T cells was significantly higher in caregivers than in controls (p < 0.0001), pointing to an unsuccessful attempt of cells to compensate the excessive loss of telomeres in caregivers. These findings demonstrate that chronic stress is associated with altered T cell function and accelerated immune cell aging as suggested by excessive telomere loss.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 A.K.D., Y.Y., H.N., Y.Z., and N.-p.W. were supported by the Intramural Research Program of the National Institute on Aging, National Institutes of Health (NIH). J.K.K.-G. and R.G. were supported in part by NIH Grant AG025732, NIH General Clinical Research Center Grant MO1-RR-0034, Comprehensive Cancer Center Core Grant CA16058, and the Gilbert and Kathryn Mitchell Endowment.
2 Address correspondence and reprint requests to Dr. Nan-ping Weng, Laboratory of Immunology, National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Drive, Baltimore, MD 21224; E-mail address: Wengn{at}mail.nih.gov or Dr. Ronald Glaser, College of Medicine, 333 West 10th Avenue, The Ohio State University, Columbus, OH 43210; E-mail address: Ronald.Glaser{at}osumc.edu
3 Abbreviations used in this paper: AD, Alzheimer’s disease; TRF, telomere restriction fragment; TRAP, telomeric repeats amplification protocol.
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