Journal
NPJ AGING AND MECHANISMS OF DISEASE
Volume 6, Issue 1, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41514-019-0041-y
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Funding
- British Heart Foundation [PG/18/25/33587, PG/15/85/31744, PG/19/15/34269]
- Newcastle Healthcare Charity
- Medical Research Council [G0500997, G0601333]
- NIHR Biomedical Research Centre in Ageing and Chronic Disease
- British Heart Foundation personal chair
- MRC [G0601333, MR/J50001X/1, G0500997] Funding Source: UKRI
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Cytomegalovirus (CMV) seropositivity in adults has been linked to increased cardiovascular disease burden. Phenotypically, CMV infection leads to an inflated CD8 T-lymphocyte compartment. We employed a 8-colour flow cytometric protocol to analyse circulating T cells in 597 octogenarians from the same birth cohort together with NT-proBNP measurements and followed all participants over 7 years. We found that, independent of CMV serostatus, a high number of CD27-CD28+ CD8 EMRA T-lymphocytes (TEMRA) protected from all-cause death after adjusting for known risk factors, such as heart failure, frailty or cancer (Hazard ratio 0.66 for highest vs lowest tertile; confidence interval 0.51-0.86). In addition, CD27-CD28+ CD8 EMRA T-lymphocytes protected from both, non-cardiovascular (hazard ratio 0.59) and cardiovascular death (hazard ratio 0.65). In aged mice treated with the senolytic navitoclax, in which we have previously shown a rejuvenated cardiac phenotype, CD8 effector memory cells are decreased, further indicating that alterations in T cell subpopulations are associated with cardiovascular ageing. Future studies are required to show whether targeting immunosenescence will lead to enhanced life- or healthspan.
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