PMC:7417788 / 15258-17641
Annnotations
{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7417788","sourcedb":"PMC","sourceid":"7417788","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7417788","text":"Aging shifts the cellular composition toward extreme effector phenotypes\nTo delineate how cell-type composition changed with aging, we separately compared the proportions of each cell type across major cell types between the YA and AA groups. We observed changes at the single-cell transcriptional level, which were further confirmed at the protein level by CyTOF. Globally, we found that TCs and BCs, especially the former, decreased by approximately 10% in all PBMCs with scRNA-seq analysis (Fig. 2A, 2B, and S5A) and by 15% with CyTOF (Figs. 2C and S5B). In contrast, MCs increased by approximately 7% in scRNA-seq analysis (Figs. 2A, 2B, and S5A) and by 10% in CyTOF (Figs. 2C and S5B).\nThe composition of cell subsets across all cell lineages differed between the YA and AA groups. Among TCs, CD4+ TCs were increased, CD8+ TCs were decreased, and CD4+CD8+ and proliferating T cells were increased in the AA group (Fig. 2B and 2C). Moreover, naive TCs, especially CD4 Naive and CD8 Naive, showed a common distribution in the YA group but were reduced in the aged group (P = 0.0175, Fig. 2D–G). Conversely, effector, memory and exhausted cell subsets were dominant in the aged group (Fig. 2H–K). The AA group also had a diminished proportion of the CD56bright NK1 population and an expansion of the NK2 and late NK3 populations (Fig. S5C and S5D). Analysis of BC clusters revealed that Naive BCs were decreased while ABCs were mildly increased in the AA group compared to the YA group (Fig. S5E and S5F).\nOur data also showed that elderly research subjects had increased MC subsets, particularly classical CD14 MCs and, to some extent, nonclassical CD16 MCs and intermediate MCs (Figs. 2L, 2M, S5G, and S5H). Overall MC growth mainly resulted from CD14 MC enrichment (P = 0.0012, Fig. 2M). However, given that CD14 MCs made up 70%–80% of the MCs population, the increase we observed in CD16 MCs was more remarkable as a change in the overall population proportion between the AA and YA groups, which was not observed for intermediate MCs between these groups (Fig. S5G–J). A similar analysis of the DC subset composition showed that the percentage of cDC2 cells increased, whereas cDC1, pDC, and pre-DC decreased with age (Figs. 2N, 2O, and S5I).\nIn summary, these results demonstrate that aging induces an immune dysfunction shift into effector and inflammatory cell 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