The age-related increase in low-grade systemic inflammation (Inflammaging) is not driven by cytomegalovirus infection.
Aging is accompanied by the development of low-grade systemic inflammation, termed 'inflammaging', characterized by raised serum C-reactive protein (CRP) and pro-inflammatory cytokines. Importantly, inflammaging is implicated in the pathogenesis of several of the major age-related diseases including cardiovascular disease, type 2 diabetes, and dementia and is associated with increased mortality. The incidence of infection with the persistent herpes virus cytomegalovirus (CMV) also increases with age. Cross-sectional studies have proposed CMV infection as a significant driver of inflammaging, but a definitive case for CMV as a causative agent in inflammaging has not yet been made. We studied longitudinally 249 subjects (153 men, 96 women) who participated in the Hertfordshire Ageing Study at baseline (1993/5, mean age 67·5 years) and at 10 year follow-up. At both times, anthropometric measurements were made and subjects provided blood samples for analysis of inflammatory status and CMV seropositivity. In the cohort as a whole, serum CRP (P < 0·02) and pro-inflammatory cytokines TNFα (P < 0·001) and IL-6 (P < 0·001) were increased between baseline and follow-up sampling whereas levels of the anti-inflammatory cytokine IL-10 were decreased (P < 0·001). These changes to cytokine status over time occurred equally in the 60% of subjects who were seropositive for CMV at baseline and follow-up, the 8% who were CMV negative at baseline but who became CMV positive by the 10 year follow-up, and also in the 32% who were CMV seronegative throughout. We conclude that CMV infection is not a primary causative factor in the age-related increase in systemic inflammation.
MRC-ARUK Centre for Musculoskeletal Ageing Research, School of Immunity and Infection, University of Birmingham, Birmingham, UK.
David B
DB
Bartlett
Charlotte M
CM
Firth
Anna C
AC
Phillips
Paul
P
Moss
Daniel
D
Baylis
Holly
H
Syddall
Avan A
AA
Sayer
Cyrus
C
Cooper
Janet M
JM
Lord
D000367:Age Factors; D000368:Aged; D002097:C-Reactive Protein / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003586:Cytomegalovirus Infections / Q000097:blood / Q000473:pathology*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000473:pathology* / Q000821:virology*; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008137:Longitudinal Studies; D008297:Male; D015800:Protozoan Proteins; D012307:Risk Factors
D016207:Cytokines; D015850:Interleukin-6; D015800:Protozoan Proteins; C072098:aginactin protein, Dictyostelium; D016753:Interleukin-10; D002097:C-Reactive Protein