The DOI matches its Crossref record; 57 of the 61 references it cites were found in a registry or an index.
Telomere/telomerase dynamics within the human immune system: Effect of chronic infection and stress
Open accessAbstract
Aging of the immune system is a major factor responsible for the increased severity of infections, reduced responses to vaccines, and higher cancer incidence in the elderly. A major category of stressors that contribute to the alterations within the T lymphocyte compartment is the family of herpes viruses. These viruses, usually acquired early in life, persist for many decades and drive certain T cells to the end stage of replicative senescence, which is characterized by a variety of phenotypic and functional changes, including altered cytokine profile, resistance to apoptosis, and shortened telomeres. Indeed, high proportions of senescent CD8 (cytotoxic) T lymphocytess are associated with latent cytomegalovirus (CMV) infection in the elderly, and are part of a cluster of immune biomarkers that are associated with early mortality. Similar cells accumulate at younger ages in persons chronically infected with HIV-1. In addition to persistent viral infection, psychological stress as well as oxidative stress can also contribute to the generation of senescent dysfunctional T lymphocytes. Strategies such as cell culture manipulation of replicative senescence, as well as lifestyle and stress reduction techniques are discussed in terms of possible approaches to enhance immune function in older persons. This review highlights the importance of using humans in studies on immunosenescence and telomere/telomerase dynamics, since model organisms employed in other facets of aging research are not subject to the particular factors that cause the striking age-related reconfiguration of the human immune system.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“HIV-associated inflammation and/or exposure to nucleoside analogues have been associated with changes in these and other key biologic pathways (33–40).”
From HIV and Aging: State of Knowledge and Areas of Critical Need for Research. A Report to the NIH Office of AIDS Research by the HIV and Aging Working Group (2012) · cites this paper as [40]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Accelerated telomere shortening in response to life stress
Epel, E. S., Blackburn, E. H., Lin, J., Dhabhar, F. S., Adler, N. E., Morrow, J. D., & Cawthon, R. M. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0407162101 · Cited by 3,002
Association between telomere length in blood and mortality in people aged 60 years or older
Cawthon, R. M., Smith, K. R., O'Brien, E., Sivatchenko, A., & Kerber, R. A. (2003) · The Lancet · doi:10.1016/s0140-6736(03)12384-7 · Cited by 1,761
The CD28 Signaling Pathway Regulates Glucose Metabolism
Frauwirth, K. A., Riley, J. L., Harris, M. H., Parry, R. V., Rathmell, J. C., Plas, D. R., Elstrom, R. L., June, C. H., & Thompson, C. B. (2002) · Immunity · doi:10.1016/s1074-7613(02)00323-0 · Cited by 1,475 · cited 2×
“…component of the immunological synapse, and is involved in a variety of T cell functions, including activation, proliferation, stabilization of cytokine messenger RNA levels, and glucose metabolism (Shimizu et al., 1992; Holdorf, Kanagawa, & Shaw, 2000; Sansom, 2000; Frauwirth et al., 2002).”
BackgroundAge-related changes in lymphocyte development and function
Linton, P. J., & Dorshkind, K. A. (2004) · Nature Immunology · doi:10.1038/ni1033 · Cited by 1,199
Arron, J. R., & Choi, Y. (2000) · Nature · doi:10.1038/35046196 · Cited by 828
Loss of telomeric DNA during aging of normal and trisomy 21 human lymphocytes.
Vaziri, H., Schächter, F., Uchida, I. A., Wei, L., Zhu, X., Effros, R. B., Cohen, D., & Harley, C. (1993) · PubMed · Cited by 737
The biology of replicative senescence
Campisi, J. (1997) · European Journal of Cancer · doi:10.1016/s0959-8049(96)00058-5 · Cited by 538
Thymic involution and immune reconstitution.
Lynch, H. E., Goldberg, G. L., Chidgey, A., Van den Brink, M. R. M., Boyd, R., & Sempowski, G. D. (2009) · Trends in Immunology · doi:10.1016/j.it.2009.04.003 · Cited by 522
Human innate immunosenescence: causes and consequences for immunity in old age
Panda, A., Arjona, A., Sapey, E., Bai, F., Fikrig, E., Montgomery, R. R., Lord, J. M., & Shaw, A. C. (2009) · Trends in Immunology · doi:10.1016/j.it.2009.05.004 · Cited by 502
Saurwein-Teissl, M., Lung, T. L., Marx, F., Gschösser, C., Asch, E., Blasko, I., Parson, W., Böck, G., Schönitzer, D., Trannoy, E., et al. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.168.11.5893 · Cited by 499
Effros, R. B., Allsopp, R., Chiu, C.-P., Hausner, M. A., Hirji, K., Wang, L., Harley, C. B., Villeponteau, B., West, M. D., & Giorgi, J. V. (1996) · AIDS · doi:10.1097/00002030-199607000-00001 · Cited by 457
Self-citationLin, J., Epel, E., Cheon, J., Kroenke, C., Sinclair, E., Bigos, M., Wolkowitz, O., Mellon, S., & Blackburn, E. (2010) · Journal of Immunological Methods · doi:10.1016/j.jim.2009.09.012 · Cited by 426
Wikby, A. (2002) · Experimental Gerontology · doi:10.1016/s0531-5565(01)00212-1 · Cited by 414
Damjanovic, A. K., Yang, Y., Glaser, R., Kiecolt‐Glaser, J. K., Nguyen, H., Laskowski, B. F., Zou, Y., Beversdorf, D. Q., & Weng, N. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.179.6.4249 · Cited by 413
Goronzy, J. J., Fulbright, J. W., Crowson, C. S., Poland, G. A., O'Fallon, W. M., & Weyand, C. M. (2001) · Journal of Virology · doi:10.1128/jvi.75.24.12182-12187.2001 · Cited by 402
Inflammation and frailty measures in older people
Hubbard, R. E., O’Mahony, M. S., Savva, G. M., Calver, B. L., & Woodhouse, K. W. (2009) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2009.00733.x · Cited by 393
Effros, R. B., Boucher, N., Porter, V., Zhu, X., Spaulding, C., Walford, R. L., Kronenberg, M., Cohen, D., & Schächter, F. (1994) · Experimental Gerontology · doi:10.1016/0531-5565(94)90073-6 · Cited by 377 · cited 2×
“Arguably, one of the most significant changes associated with T lymphocyte replicative senescence in cell culture is the complete and irreversible loss of expression of the major signaling molecule, CD28 (Effros et al., 1994a; Vallejo, Nestel, Schirmer, Weyand, & Goronzy, 1998).”
BackgroundThe Immune System in Health and Disease
Janeway, C. A., Travers, P. J., Walport, M. J., & Shlomchik, M. J. (2001) · Cited by 374
CD28, CTLA‐4 and their ligands: who does what and to whom?
Sansom, D. M. (2000) · Immunology · doi:10.1046/j.1365-2567.2000.00121.x · Cited by 374
Replicative senescence of T cells: does the Hayflick Limit lead to immune exhaustion?
Effros, R. B., & Pawelec, G. (1997) · Immunology Today · doi:10.1016/s0167-5699(97)01079-7 · Cited by 337
The role of CD8+ T‐cell replicative senescence in human aging
Effros, R. B., Dagarag, M., Spaulding, C., & Man, J. (2005) · Immunological Reviews · doi:10.1111/j.0105-2896.2005.00259.x · Cited by 336
Can Meditation Slow Rate of Cellular Aging? Cognitive Stress, Mindfulness, and Telomeres
Epel, E., Daubenmier, J., Moskowitz, J. T., Folkman, S., & Blackburn, E. (2009) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2009.04414.x · Cited by 324
Immune Dysregulation and Chronic Stress among Older Adults: A Review
Gouin, J.-P., Hantsoo, L. V., & Kiecolt‐Glaser, J. K. (2008) · NeuroImmunoModulation · doi:10.1159/000156468 · Cited by 320
Is immunosenescence infectious?
Pawelec, G., Akbar, A. N., Caruso, C., Effros, R. B., Grubeck‐Loebenstein, B., & Wikby, A. (2004) · Trends in Immunology · doi:10.1016/j.it.2004.05.006 · Cited by 260
Spaulding, C., Guo, W., & Effros, R. B. (1999) · Experimental Gerontology · doi:10.1016/s0531-5565(99)00033-9 · Cited by 258
Valenzuela, H. (2002) · Clinical Immunology · doi:10.1006/clim.2002.5271 · Cited by 254
Ouyang, Q., Wagner, W. M., Wikby, A., Walter, S., Aubert, G., Dodi, A. I., Travers, P. J., & Pawelec, G. (2003) · Journal of Clinical Immunology · doi:10.1023/a:1024580531705 · Cited by 239
CD28 Expression in T Cell Aging and Human Longevity
Boucher, N., Dufeu-Duchesne, T., Vicaut, E., Farge, D., Effros, R. B., & Schächter, F. (1998) · Experimental Gerontology · doi:10.1016/s0531-5565(97)00132-0 · Cited by 194 · cited 1×
“Within memory T lymphocyte pool, there is a striking change in the phenotype and function of the so-called CD8, or cytotoxic T lymphocytes, with progressively increasing proportions of cells with features of replicative senescence (Boucher et al., 1998).”
BackgroundCrosslinking of the T cell-specific accessory molecules CD7 and CD28 modulates T cell adhesion.
Shimizu, Y., van Seventer, G. A., Ennis, E. A., Newman, W., Horgan, K. J., & Shaw, S. (1992) · The Journal of Experimental Medicine · doi:10.1084/jem.175.2.577 · Cited by 190
Vallejo, A. N., Nestel, A. R., Schirmer, M., Weyand, C. M., & Goronzy, J. J. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.14.8119 · Cited by 179
Telomerase-Based Pharmacologic Enhancement of Antiviral Function of Human CD8+ T Lymphocytes
Fauce, S. R., Jamieson, B. D., Chin, A. C., Mitsuyasu, R. T., Parish, S. T., Ng, H. L., Ramirez, C. M., Yang, O. O., Harley, C. B., & Effros, R. B. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.181.10.7400 · Cited by 171
Tsukishiro, T., Donnenberg, A. D., & Whiteside, T. L. (2003) · Cancer Immunology, Immunotherapy · doi:10.1007/s00262-003-0395-6 · Cited by 158
Irwin, M. R., Olmstead, R. E., & Oxman, M. N. (2007) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2007.01109.x · Cited by 153
Human T lymphocytes possess a limited in vitro life span
Perillo, N. L., Walford, R. L., Newman, M. A., & Effros, R. B. (1989) · Experimental Gerontology · doi:10.1016/0531-5565(89)90009-0 · Cited by 120
Intrinsic versus environmental influences on T‐cell responses in aging
Linton, P., Li, S. P., Zhang, Y., Bautista, B., Huynh, Q. L., & Trinh, T. (2005) · Immunological Reviews · doi:10.1111/j.0105-2896.2005.00266.x · Cited by 115
Maini, M. K., Soares, M. V. D., Zilch, C. F., Akbar, A. N., & Beverley, P. C. L. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.162.8.4521 · Cited by 110
Pawelec, G., Adibzadeh, M., Solana, R., & Beckman, I. (1997) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(96)01812-x · Cited by 109
Dagarag, M. D., Evazyan, T., Rao, N. P., & Effros, R. B. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.173.10.6303 · Cited by 107
Molecular characterization of allospecific T suppressor and tolerogenic dendritic cells: review
Suciu‐Foca, N., Manavalan, J. S., Scotto, L., Kim‐Schulze, S., Galluzzo, S., Naiyer, A. J., Fan, J., Vlad, G., & Cortesini, R. (2004) · International Immunopharmacology · doi:10.1016/j.intimp.2004.09.003 · Cited by 102
Li, Y., Liu, S., Hernandez, J., Vence, L. M., Hwu, P., & Radvanyi, L. G. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0901101 · Cited by 97
Association of Longer Telomeres With Better Health in Centenarians
Terry, D. F., Nolan, V. G., Andersen, S. L., Perls, T. T., & Cawthon, R. (2008) · The Journals of Gerontology Series A · doi:10.1093/gerona/63.8.809 · Cited by 97
Oxidized lipids enhance RANKL production by T lymphocytes: Implications for lipid-induced bone loss
Graham, L. S., Parhami, F., Tintut, Y., Ramirez, C. M., Demer, L. L., & Effros, R. B. (2009) · Clinical Immunology · doi:10.1016/j.clim.2009.07.011 · Cited by 93
Modulation of T Lymphocyte Replicative Senescence via TNF-α Inhibition: Role of Caspase-3
Parish, S. T., Wu, J. E., & Effros, R. B. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0803449 · Cited by 86
Dagarag, M. D., Ng, H. L., Lubong, R., Effros, R. B., & Yang, O. O. (2003) · Journal of Virology · doi:10.1128/jvi.77.5.3077-3083.2003 · Cited by 85
Decreased perforin and granzyme B expression in senescent HIV-1-specific cytotoxic T lymphocytes
Yang, O. O., Lin, H., Dagarag, M., Ng, H. L., Effros, R. B., & Uittenbogaart, C. H. (2005) · Virology · doi:10.1016/j.virol.2004.11.028 · Cited by 79
Control of fibroblast senescence and activation of programmed cell death
Wang, E., Lee, M., & Pandey, S. (1994) · Journal of Cellular Biochemistry · doi:10.1002/jcb.240540410 · Cited by 78
Stress Response of Senescent T Lymphocytes Reduced hsp70 Is Independent of the Proliferative Block
Effros, R. B., Zhu, X., & Walford, R. L. (1994) · Journal of Gerontology · doi:10.1093/geronj/49.2.b65 · Cited by 72
Cutting Edge: Antigen-Dependent Regulation of Telomerase Activity in Murine T Cells
Hathcock, K. S., Weng, N., Merica, R. R., Jenkins, M. K., & Hodes, R. J. (1998) · The Journal of Immunology · doi:10.4049/jimmunol.160.12.5702 · Cited by 69
Perillo, N. L., Naeim, F., Walford, R. L., & Effros, R. B. (1993) · Mechanisms of Ageing and Development · doi:10.1016/0047-6374(93)90121-7 · Cited by 63
Kleemeier Award Lecture 2008 – the canary in the coal mine: telomeres and human healthspan
Effros, R. B. (2009) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/glp001 · Cited by 58
McElhaney, J. E. (1998) · Vaccine · doi:10.1016/s0264-410x(98)00133-9 · Cited by 54
Characiejus, D., Pašukonienė, V., Kazlauskaitė, N., Valuckas, K. P., Petraitis, T., Mauricas, M., & Otter, W. D. (2002) · PubMed · Cited by 53
Age related microsatellite instability in T cells from healthy individuals
Krichevsky, S., Pawelec, G., Gural, A., Effros, R. B., Globerson, A., Yehuda, D. B., & Ben‐Yehuda, A. (2004) · Experimental Gerontology · doi:10.1016/j.exger.2003.12.016 · Cited by 52
Cortesini, R., Renna-Molajoni, E., Cinti, P., Pretagostini, R., Ho, E. K., Rossi, P. C., & Cortesini, N. S.-F. (2002) · Human Immunology · doi:10.1016/s0198-8859(02)00442-1 · Cited by 44
Adibzadeh, M., Mariani, E., Bartoloni, C., Beckman, I., Ligthart, G. J., Remarque, E. J., Shall, S., Solana, R., Taylor, G. M., Barnett, Y., et al. (1996) · Mechanisms of Ageing and Development · doi:10.1016/0047-6374(96)01783-6 · Cited by 35
The adaptor protein shc is involved in the negative regulation of NK cell-mediated cytotoxicity
Galandrini, R., Tassi, I., Morrone, S., Lanfrancone, L., Pelicci, P. G., Piccoli, M., Frati, L., & Santoni, A. (2001) · European Journal of Immunology · doi:10.1002/1521-4141(200107)31:7 · Cited by 32
CD28 and T cell co-stimulation.
Holdorf, A. D., Kanagawa, O., & Shaw, A. S. (2000) · PubMed · Cited by 26
Research works printed but not linked: 1
- Lin, 2009, Analyses and comparisons of telomerase activity and telomere length in human T and B cells: insights for epidemiology of telomere maintenance, J. Immunol. Methods
Cited by
Sorted by citations
Cellular Senescence: Aging, Cancer, and Injury
Calcinotto, A., Kohli, J., Zagato, E., Pellegrini, L., Demaria, M., & Alimonti, A. (2019) · Physiological Reviews · doi:10.1152/physrev.00020.2018 · Cited by 1,270
Immunosenescence: molecular mechanisms and diseases
Liu, Z., Liang, Q., Ren, Y., Guo, C., Ge, X., Wang, L., Cheng, Q., Luo, P., Zhang, Y., & Han, X. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01451-2 · Cited by 1,082
High, K. P., Brennan-Ing, M., Clifford, D. B., Cohen, M. H., Currier, J., Deeks, S. G., Deren, S., Effros, R. B., Gebo, K., Goronzy, J. J., et al. (2012) · JAIDS Journal of Acquired Immune Deficiency Syndromes · doi:10.1097/qai.0b013e31825a3668 · Cited by 522
Self-citationStrioga, M., Pasukoniene, V., & Characiejus, D. (2011) · Immunology · doi:10.1111/j.1365-2567.2011.03470.x · Cited by 505
From “truly naïve” to “exhausted senescent” T cells: When markers predict functionality
Larbi, A., & Fulop, T. (2014) · Cytometry Part A · doi:10.1002/cyto.a.22351 · Cited by 359
Metadata
- Authors
- Effros, R. B.
- Affiliations
- University of California, Los Angeles (US)
- Corresponding author
- Effros, Rita B.
- ORCID
- Effros, Rita B.
- Venue
- Experimental Gerontology
- Publisher
- Elsevier BV
- Published
- 2011-02
- Volume
- 46
- Issue
- 2-3
- Pages
- 135-140
- ISSN
- 0531-5565 (ISSN-L)
- PMC
- PMC3246363
- OpenAlex
- W2070439612
- Cited by
- 137
- References
- 61
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 3 · 2023: 7 · 2022: 1 · 2021: 9 · 2020: 7 · 2019: 9 · 2018: 9 · 2017: 12 · 2016: 13 · 2015: 8 · 2014: 13 · 2013: 16 · 2012: 14
- FWCI
- 1.32
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Experimental Gerontology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (R01AG023720, AG 023720)
- National Institute of Allergy and Infectious Diseases (R01AI060362, AI 060362)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Epidemiology › Cytomegalovirus and herpesvirus research
- Keywords
- immunosenescence, telomeres, telomerase, replicative senescence, T cells, cytomegalovirus, HIV-1, chronic viral infection, psychological stress, oxidative stress, CD8+ T cells, aging, stress reduction
- MeSH terms
- Aging, Humans, Immune System, T-Lymphocytes, Virus Diseases, Telomere, Virus Latency, Telomerase, Cell Proliferation
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review