Cytomegalovirus infection is associated with increased mortality in the older population
Abstract
Summary: Cytomegalovirus ( CMV ) is a common herpesvirus infection and stimulates the expansion of very large numbers of CMV ‐specific T cells that reduce the CD 4/ CD 8 ratio and suppress the number of naïve T cells. CMV infection has been associated with frailty and impaired survival. We investigated the correlates of CMV and the impact of the CMV infection on mortality within a cohort of 511 individuals aged at least 65 years who were followed up for 18 years. The mean age of the participants was 74 years of which 70% were CMV ‐seropositive. CMV was strongly linked to socio‐economic status, and CMV infection increased the annual mortality rate by 42% (Hazard ratio = 1.42, 95% CI : 1.11–1.76 after adjusting for age, sex and baseline socio‐economic and health variables) corresponding to 3.7 years lower life expectancy from age 65. Infection was associated with a near doubling of cardiovascular deaths, whereas there was no increase in mortality from other causes. These results show that CMV infection markedly increases the mortality rate in healthy older individuals due to an excess of vascular deaths. These findings may have significant implications for the study of immune senescence and if confirmed more generally could have important implications for measures to optimize the health of the elderly.
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Cytomegalovirus infection has been directly linked with increased inflammatory activity, poor responses to vaccination, frailty, accelerated cognitive decline, and early mortality.
“These changes are largely driven by infection with Cytomegalovirus, which has been directly linked with increased inflammatory activity, poor responses to vaccination, frailty, accelerated cognitive decline, and early mortality.”
From Is immunosenescence influenced by our lifetime “dose” of exercise? (2016) · cites this paper as Savva et al. 2013
Many features of an ageing immune system appear to be driven by CMV, and infection with this virus alone has since been associated with frailty, cognitive impairment, poor responses to vaccination in young and elderly individuals, and ultimately earlier mortality.
“Indeed many features of an ageing immune system appear to be driven by CMV, and infection with this virus alone has since been associated with frailty (Haeseker et al. 2013), cognitive impairment (Gow et al. 2013), poor responses to vaccination in young and elderly individuals (Derhovanessian et al. 2012; Frasca et al. 2015; Moro-Garcia et al. 2012; Turner et al. 2014b; Wald et al. 2013), and”
From Is immunosenescence influenced by our lifetime “dose” of exercise? (2016) · cites this paper as Savva et al. 2013
Cites
A Proportional Hazards Model for the Subdistribution of a Competing Risk
Fine, J. P., & Gray, R. J. (1999) · Journal of the American Statistical Association · doi:10.1080/01621459.1999.10474144 · Cited by 14,290 · see citing works
Review of cytomegalovirus seroprevalence and demographic characteristics associated with infection
Cannon, M. J., Schmid, D. S., & Hyde, T. B. (2010) · Reviews in Medical Virology · doi:10.1002/rmv.655 · Cited by 1,495 · see citing works
Immunobiology of Human Cytomegalovirus: from Bench to Bedside
Crough, T., & Khanna, R. (2009) · Clinical Microbiology Reviews · doi:10.1128/cmr.00034-08 · Cited by 647 · see citing works
Choice of time‐scale in Cox's model analysis of epidemiologic cohort data: a simulation study
Thiébaut, A. C. M., & Bénichou, J. (2004) · Statistics in Medicine · doi:10.1002/sim.2098 · Cited by 633 · see citing works
Gillespie, G. M. A., Wills, M. R., Appay, V., O’Callaghan, C. A., Murphy, M., Smith, N. T., Sissons, P., Rowland‐Jones, S., Bell, J. I., & Moss, P. A. H. (2000) · Journal of Virology · doi:10.1128/jvi.74.17.8140-8150.2000 · Cited by 419 · see citing works
Self-citationWikby, A. (2002) · Experimental Gerontology · doi:10.1016/s0531-5565(01)00212-1 · Cited by 414 · see citing works
Simanek, A. M., Dowd, J. B., Pawelec, G., Melzer, D. R., Dutta, A., & Aiello, A. E. (2011) · PLoS ONE · doi:10.1371/journal.pone.0016103 · Cited by 398 · see citing works
Khan, N., Hislop, A. D., Gudgeon, N. H., Cobbold, M., Khanna, R., Nayak, L., Rickinson, A. B., & Moss, P. A. H. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.173.12.7481 · Cited by 351 · see citing works
Self-citationBartlett, D. B., Firth, C. M., Phillips, A. C., Moss, P., Baylis, D., Syddall, H., Sayer, A. A., Cooper, C., & Lord, J. M. (2012) · Aging Cell · doi:10.1111/j.1474-9726.2012.00849.x · Cited by 278 · see citing works
Self-citationWang, G. C., Kao, W. H. L., Murakami, P. N., Xue, Q., Chiou, R. B., Detrick, B., McDyer, J. F., Semba, R. D., Casolaro, V., Walston, J. D., et al. (2010) · American Journal of Epidemiology · doi:10.1093/aje/kwq062 · Cited by 266 · see citing works
Chidrawar, S. M., Khan, N., Wei, W., McLarnon, A., Smith, N., Nayak, L., & Moss, P. A. H. (2009) · Clinical & Experimental Immunology · doi:10.1111/j.1365-2249.2008.03785.x · Cited by 244 · see citing works
Self-citationSchmaltz, H. N., Fried, L. P., Xue, Q., Walston, J. D., Leng, S. X., & Semba, R. D. (2005) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2005.53250.x · Cited by 240 · see citing works
The Burden of Diseases on Disability-Free Life Expectancy in Later Life
Jagger, C., Matthews, R. J., Matthews, F. E., Robinson, T. G., Robine, J., & Brayne, C. (2007) · The Journals of Gerontology Series A · doi:10.1093/gerona/62.4.408 · Cited by 178 · see citing works
Self-citationVescovini, R., Biasini, C., Fagnoni, F. F., Telera, A. R., Zanlari, L., Pedrazzoni, M., Bucci, L., Monti, D., Medici, M. C., Chezzi, C., et al. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.179.6.4283 · Cited by 173 · see citing works
Potena, L., Holweg, C., Chin, C. C., et al. (2006) · Transplantation · doi:10.1097/01.tp.0000229039.87735.76 · Cited by 153 · see citing works
Smieja, M., Gnarpe, J. A., Lonn, E., Gnarpe, H., Olsson, G. O., Yi, Q., Džavík, V., McQueen, M., & Yusuf, S. (2003) · Circulation · doi:10.1161/01.cir.0000044940.65226.1f · Cited by 149 · see citing works
Weinberger, B., Lazuardi, L., Weiskirchner, I., Keller, M., Neuner, C., Fischer, K.-H., Neuman, B., Würzner, R., & Grubeck‐Loebenstein, B. (2006) · Human Immunology · doi:10.1016/j.humimm.2006.10.019 · Cited by 138 · see citing works
The detection of CMV pp65 and IE1 in glioblastoma multiforme
Lucas, K. G., Bao, L., Bruggeman, R., et al. (2010) · Journal of Neuro-Oncology · doi:10.1007/s11060-010-0383-6 · Cited by 137 · see citing works
Cologne, J., Hsu, W.-L., Abbott, R. D., Ohishi, W., Grant, E. J., Fujiwara, S., & Cullings, H. M. (2012) · Epidemiology · doi:10.1097/ede.0b013e318253e418 · Cited by 127 · see citing works
Streblow, D. N., Dumortier, J., Moses, A. V., Orloff, S. L., & Nelson, J. A. (2008) · Current Topics in Microbiology and Immunology · doi:10.1007/978-3-540-77349-8_22 · Cited by 125 · see citing works
Human Cytomegalovirus Seropositivity Is Associated With Impaired Vascular Function
Grahame-Clarke, C. N., Chan, N. N., Andrew, D., Ridgway, G. L., Betteridge, D. J., Emery, V. C., Colhoun, H. M., & Vallance, P. J. (2003) · Circulation · doi:10.1161/01.cir.0000084505.54603.c7 · Cited by 118 · see citing works
Strandberg, T. E., Pitkälä, K. H., & Tilvis, R. S. (2009) · JAMA · doi:10.1001/jama.2009.4 · Cited by 116 · see citing works
Haider, A. W., Wilson, P. W. F., Larson, M. G., Evans, J. C., Michelson, E. L., Wolf, P. A., O’Donnell, C. J., & Levy, D. A. (2002) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(02)02272-6 · Cited by 110 · see citing works
Survival in a population sample is predicted by proportions of lymphocyte subsets
Huppert, F. A. (2003) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(03)00021-6 · Cited by 85 · see citing works
Self-citationTrzonkowski, P., Myśliwska, J. M., Pawelec, G., & Myśliwski, A. (2008) · Biogerontology · doi:10.1007/s10522-008-9155-5 · Cited by 64 · see citing works
Changes in Epstein-Barr Virus Antibody Titers Associated with Aging
Glaser, R., Strain, E. C., Tarr, K. L., et al. (1985) · Experimental Biology and Medicine · doi:10.3181/00379727-179-42108 · Cited by 62 · see citing works
Betjes, M. G. H., de Wit, E. A., Weimar, W. W., & Litjens, N. H. R. (2010) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfq203 · Cited by 58 · see citing works
Effects of herpes virus carrier status on peripheral T lymphocyte subsets
Gratama, J. W., Naipal, A. M., Oosterveer, M. A. P., Stijnen, T., Kluin‐Nelemans, H. C., Ginsel, L. A., Ottolander, G. J. D., Hekker, A. C., D'Amaro, J., & van der Giessen, M. (1987) · Blood · doi:10.1182/blood.v70.2.516.516 · Cited by 53 · see citing works
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Shrock, E., Fujimura, E., Kula, T., Timms, R. T., Lee, I.-H., Leng, Y., Robinson, M. L., Sie, B. M., Li, M. Z., Chen, Y., et al. (2020) · Science · doi:10.1126/science.abd4250 · Cited by 678 · see citing works
The chromatin accessibility signature of human immune aging stems from CD8+ T cells
Ucar, D., Márquez, E. J., Chung, C.-H., Marches, R., Rossi, R. J., Uyar, A., Wu, T.-C., George, J., Stitzel, M. L., Palucka, A. K., et al. (2017) · Journal of Experimental Medicine · doi:10.1084/jem.20170416 · Cited by 200 · see citing works
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Weyand, C. M., Yang, Z., & Goronzy, J. J. (2014) · Current Opinion in Rheumatology · doi:10.1097/bor.0000000000000011 · Cited by 164 · see citing works
DNA damage response (DDR) and senescence: shuttled inflamma-miRNAs on the stage of inflamm-aging
Olivieri, F., Albertini, M. C., Orciani, M., Ceka, A., Cricca, M., Procopio, A. D., & Bonafè, M. (2015) · Oncotarget · doi:10.18632/oncotarget.5899 · Cited by 163 · see citing works
New advances in CMV and immunosenescence
Sansoni, P., Vescovini, R., Fagnoni, F. F., Akbar, A., Arens, R., Chiu, Y.-L., Čičin-Šain, L., Dechanet-Merville, J., Derhovanessian, E., Ferrando-Martinez, S., et al. (2014) · Experimental Gerontology · doi:10.1016/j.exger.2014.03.020 · Cited by 150 · see citing works
Self-citationSpyridopoulos, I., Martin‐Ruiz, C., Hilkens, C., Yadegarfar, M. E., Isaacs, J., Jagger, C., Kirkwood, T., & von Zglinicki, T. (2016) · Aging Cell · doi:10.1111/acel.12430 · Cited by 133 · see citing works
Parry, H. M., Zuo, J., Frumento, G., Mirajkar, N., Inman, C., Edwards, E., Griffiths, M., Pratt, G., & Moss, P. (2016) · Immunity & Ageing · doi:10.1186/s12979-015-0056-6 · Cited by 125 · see citing works
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Turner, J. E. (2016) · Biogerontology · doi:10.1007/s10522-016-9642-z · Cited by 112 · see citing works
Broadley, I., Pera, A., Morrow, G., Davies, K. A., & Kern, F. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00195 · Cited by 103 · see citing works
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Covre, L. P., De Maeyer, R. P. H., Gomes, D. C. O., & Akbar, A. N. (2020) · Aging Cell · doi:10.1111/acel.13272 · Cited by 93 · see citing works
Impact of Aging and Cytomegalovirus on Immunological Response to Influenza Vaccination and Infection
Merani, S., Pawelec, G., Kuchel, G. A., & McElhaney, J. E. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00784 · Cited by 74 · see citing works
The Effect of Chronic Cytomegalovirus Infection on Pneumococcal Vaccine Responses
O'Connor, D., Trück, J., Lazarus, R., Clutterbuck, E. A., Voysey, M., Jeffery, K., & Pollard, A. J. (2014) · The Journal of Infectious Diseases · doi:10.1093/infdis/jit673 · Cited by 22 · see citing works
- Authors
- Savva, G. M., Pachnio, A., Kaul, B., Morgan, K., Huppert, F. A., Brayne, C., & Moss, P. A. H.
- Affiliations
- University of Cambridge (GB)
- University of Birmingham (GB)
- Loughborough University (GB)
- Corresponding author
- Moss, Paul A. H.
- Venue
- Aging Cell
- Publisher
- Wiley
- Published
- 2013-04-19
- Volume
- 12
- Issue
- 3
- Pages
- 381-387
- ISSN
- 1474-9718 (ISSN-L)
- 1474-9726
- OpenAlex
- W2025593432
- Cited by
- 216
- References
- 28
- Citations by year
- 2026: 7 · 2025: 14 · 2024: 6 · 2023: 11 · 2022: 11 · 2021: 25 · 2020: 22 · 2019: 13 · 2018: 22 · 2017: 16 · 2016: 27 · 2015: 17 · 2014: 19 · 2013: 6
- FWCI
- 16.79
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Aging Cell (publishedVersion)
- PubMed (publishedVersion)
- Research Bank (Australian Catholic University) (submittedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- UEA Digital Repository (University of East Anglia) (submittedVersion)
- Funders
- National Institute for Health and Care Research (NF-SI-0611-10084)
- Medical Research Council
- Topics
- Health Sciences › Medicine › Epidemiology › Cytomegalovirus and herpesvirus research
- Health Sciences › Medicine › Oncology › Viral-associated cancers and disorders
- Health Sciences › Medicine › Epidemiology › Herpesvirus Infections and Treatments
- Keywords
- cytomegalovirus infection, mortality, older adults, cardiovascular mortality, immunosenescence, socioeconomic status, life expectancy, frailty, CD4/CD8 ratio, T cell depletion, seroprevalence
- MeSH terms
- Age Factors, Aged, Aged, 80 and over, Aging, Antibodies, Viral, Cardiovascular Diseases, Cytomegalovirus Infections, Cytomegalovirus, Female, Humans, Male, CD4-Positive T-Lymphocytes, Survival Analysis, Frail Elderly, CD4-CD8 Ratio, CD8-Positive T-Lymphocytes
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