Are the Healthy Vulnerable? Cytomegalovirus Seropositivity in Healthy Adults Is Associated With Accelerated Epigenetic Age and Immune Dysregulation.
COVID-19
biologic age
cytomegalovirus
epigenetic age
immune dysregulation
seropositivity
Journal
The Journal of infectious diseases
ISSN: 1537-6613
Titre abrégé: J Infect Dis
Pays: United States
ID NLM: 0413675
Informations de publication
Date de publication:
01 02 2022
01 02 2022
Historique:
received:
03
03
2021
accepted:
12
07
2021
pubmed:
14
7
2021
medline:
10
2
2022
entrez:
13
7
2021
Statut:
ppublish
Résumé
Evaluating age as a risk factor for susceptibility to infectious diseases, particularly coronavirus disease 2019 (COVID-19), is critical. Cytomegalovirus (CMV) serologic prevalence increases with age and associates with inflammatory-mediated diseases in the elderly. However, little is known regarding the subclinical impact of CMV and risk it poses to healthy older adults. Prior to the COVID-19 pandemic we conducted a study to determine the association of CMV to biologic age and immune dysregulation. Community-dwelling, healthy adults older than 60 years were evaluated using DNA methylation assays to define epigenetic age (EpiAge) and T-cell immunophenotyping to assess immune dysregulation. All subjects were healthy and asymptomatic. Those CMV seropositive had more lymphocytes, CD8 T cells, CD28- T cells, decreased CD4:CD8 cell ratios, and had higher average EpiAge (65.34 years) than those CMV seronegative (59.53 years). Decreased percent CD4 (P = .003) and numbers of CD4 T cells (P = .0199) correlated with increased EpiAge. Our novel findings distinguish altered immunity in the elderly based on CMV status. Chronic CMV infection in healthy, older adults is associated with indicators of immune dysregulation, both of which correlate to differences in EpiAge.
Sections du résumé
BACKGROUND
Evaluating age as a risk factor for susceptibility to infectious diseases, particularly coronavirus disease 2019 (COVID-19), is critical. Cytomegalovirus (CMV) serologic prevalence increases with age and associates with inflammatory-mediated diseases in the elderly. However, little is known regarding the subclinical impact of CMV and risk it poses to healthy older adults. Prior to the COVID-19 pandemic we conducted a study to determine the association of CMV to biologic age and immune dysregulation.
METHODS
Community-dwelling, healthy adults older than 60 years were evaluated using DNA methylation assays to define epigenetic age (EpiAge) and T-cell immunophenotyping to assess immune dysregulation.
RESULTS
All subjects were healthy and asymptomatic. Those CMV seropositive had more lymphocytes, CD8 T cells, CD28- T cells, decreased CD4:CD8 cell ratios, and had higher average EpiAge (65.34 years) than those CMV seronegative (59.53 years). Decreased percent CD4 (P = .003) and numbers of CD4 T cells (P = .0199) correlated with increased EpiAge.
CONCLUSIONS
Our novel findings distinguish altered immunity in the elderly based on CMV status. Chronic CMV infection in healthy, older adults is associated with indicators of immune dysregulation, both of which correlate to differences in EpiAge.
Identifiants
pubmed: 34255838
pii: 6320592
doi: 10.1093/infdis/jiab365
pmc: PMC8344607
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
443-452Subventions
Organisme : CIHR
ID : 40996
Pays : Canada
Organisme : Anna-Maria Solinas Laroche Allergy and Clinical Immunology Research Fund
Organisme : Montreal General Hospital Foundation
Informations de copyright
© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.
Références
J Infect Dis. 2015 Nov 15;212(10):1563-73
pubmed: 25969563
Nat Rev Genet. 2018 Jun;19(6):371-384
pubmed: 29643443
Curr HIV/AIDS Rep. 2016 Feb;13(1):10-9
pubmed: 26810437
Nat Rev Immunol. 2016 Jun;16(6):367-77
pubmed: 27108521
Rev Med Virol. 2010 Jul;20(4):202-13
pubmed: 20564615
Front Microbiol. 2016 Dec 27;7:2111
pubmed: 28082969
J Gerontol A Biol Sci Med Sci. 2015 Feb;70(2):143-54
pubmed: 24568932
J Gerontol A Biol Sci Med Sci. 2017 Aug 1;72(8):1015-1023
pubmed: 27672102
Clin Infect Dis. 2013 May;56(10):1421-7
pubmed: 23442763
J Med Virol. 2020 Apr;92(4):441-447
pubmed: 31994742
Exp Gerontol. 2002 Jan-Mar;37(2-3):445-53
pubmed: 11772532
Aging Cell. 2012 Dec;11(6):1132-4
pubmed: 23061750
J Clin Invest. 1998 Jan 15;101(2):497-502
pubmed: 9435323
Viruses. 2017 Oct 05;9(10):
pubmed: 28981470
PLoS One. 2011 Feb 17;6(2):e16103
pubmed: 21379581
Sex Transm Dis. 1998 Oct;25(9):476-80
pubmed: 9800259
Vox Sang. 2004 Jan;86(1):41-4
pubmed: 14984558
Mech Ageing Dev. 1984 Nov;28(1):47-55
pubmed: 6513613
Biochem Soc Trans. 2003 Apr;31(2):449-51
pubmed: 12653659
Immune Netw. 2015 Aug;15(4):186-90
pubmed: 26330804
Int J Mol Sci. 2017 Aug 10;18(8):
pubmed: 28796199
J Clin Invest. 2011 Aug;121(8):3109-19
pubmed: 21785218
Exp Gerontol. 2007 Aug;42(8):753-61
pubmed: 17606347
J Leukoc Biol. 2012 Feb;91(2):197-205
pubmed: 22013229
Curr Opin Immunol. 2012 Aug;24(4):476-81
pubmed: 22554789
J Gerontol A Biol Sci Med Sci. 2005 May;60(5):556-65
pubmed: 15972602
J Exp Med. 2005 Sep 5;202(5):673-85
pubmed: 16147978
Exp Gerontol. 2015 Dec;72:227-9
pubmed: 26485162
Braz J Med Biol Res. 2003 Jun;36(6):795-805
pubmed: 12792710
J Infect Dis. 2017 Sep 1;216(5):565-572
pubmed: 28931225
Clin Infect Dis. 2000 Aug;31(2):578-85
pubmed: 10987724
J Comp Pathol. 2010 Jan;142 Suppl 1:S39-44
pubmed: 19897208
J Infect Dis. 2011 May 15;203(10):1474-83
pubmed: 21502083
PLoS One. 2015 Feb 03;10(2):e0117039
pubmed: 25647167
J Immunol. 2004 Dec 15;173(12):7481-9
pubmed: 15585874
J Gerontol A Biol Sci Med Sci. 1995 Nov;50(6):B378-82
pubmed: 7583794
J Infect Dis. 2016 Nov 1;214(9):1430-1437
pubmed: 27521364
Clin Microbiol Rev. 2013 Jan;26(1):86-102
pubmed: 23297260
MMWR Morb Mortal Wkly Rep. 2020 Mar 27;69(12):343-346
pubmed: 32214079
Med Microbiol Immunol. 2012 Nov;201(4):551-66
pubmed: 22991040
J Virol. 2005 Mar;79(6):3675-83
pubmed: 15731261
PLoS One. 2014 Sep 22;9(9):e107167
pubmed: 25244034
N Engl J Med. 2017 Dec 21;377(25):2433-2444
pubmed: 29211658