Journal
AGING CELL
Volume 21, Issue 5, Pages -Publisher
WILEY
DOI: 10.1111/acel.13607
Keywords
biomarkers; CD8(+) T-cells; CMV; epigenetics; human aging; inflammation
Categories
Funding
- Estonian Research Council [PRG377, PRG1095, PRG1117, PSG59, TK142]
- European Regional Development Fund, EXCEGEN [2014-2020.4.01.15-0012]
Ask authors/readers for more resources
Age-related changes in T-cell populations play an important role in immunosenescence. CD8(+) TEMRA cells and their subsets have characteristics of cellular senescence and increase in older individuals and age-related chronic inflammatory diseases. CD8(+) TEMRA proportions correlate with cytomegalovirus (CMV) antibody levels but not with chronological age. TRANCE/RANKL levels are associated with differentiated T-cell populations, including CD8(+) TEMRA and its CD28(-) subsets. Deep-amplicon bisulfite sequencing can be used to predict CD8(+) TEMRA cell proportions as a biomarker of immunosenescence.
Age-related changes in human T-cell populations are important contributors to immunosenescence. In particular, terminally differentiated CD8(+) effector memory CD45RA(+) TEMRA cells and their subsets have characteristics of cellular senescence, accumulate in older individuals, and are increased in age-related chronic inflammatory diseases. In a detailed T-cell profiling among individuals over 65 years of age, we found a high interindividual variation among CD8(+) TEMRA populations. CD8(+) TEMRA proportions correlated positively with cytomegalovirus (CMV) antibody levels, however, not with the chronological age. In the analysis of over 90 inflammation proteins, we identified plasma TRANCE/RANKL levels to associate with several differentiated T-cell populations, including CD8(+) TEMRA and its CD28(-) subsets. Given the strong potential of CD8(+) TEMRA cells as a biomarker for immunosenescence, we used deep-amplicon bisulfite sequencing to match their frequencies in flow cytometry with CpG site methylation levels and developed a computational model to predict CD8(+) TEMRA cell proportions from whole blood genomic DNA. Our findings confirm the association of CD8(+) TEMRA and its subsets with CMV infection and provide a novel tool for their high throughput epigenetic quantification as a biomarker of immunosenescence.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available