Reporting on the Immune System Composition of Centenarians
Centenarians exhibit some different immune systems characteristics when compared against the general population in earlier old age. Whether this offers any meaningful degree of protection is an open question. Even if these differences are protective, one should expect that biochemical characteristics that are found to a greater degree in centenarians will only slightly improve the small odds of living to be this old in the context of the medical technology and lifestyle choices of the last century. It doesn't take much of a change, say 1.25% survival odds rather than 1% survival odds, to see a lot more of that mechanism operating in the living population very old people, when compared to the population at large. That doesn't make the underlying mechanism a desirable basis for an enhancement therapy - it is achieving far too little to be worth the time and effort.
Using a multi-modal, single cell approach, we generated cell composition and transcriptional profiles from the peripheral blood mononuclear cells (PBMCs) of 7 centenarians using CITE-seq. We integrated this novel data set with publicly available single cell RNA-seq datasets of aging and longevity across the human lifespan to characterize cell type composition and gene expression profiles unique to centenarians. The peripheral blood immune cell repertoire of individuals is known to change with age. Previous transcriptional studies have shown decreases in lymphocytes and increases in myeloid cells with age, which we also observed in the peripheral blood of centenarians. However, in addition to these common changes across aging, our analysis identified patterns of immune cell profiles and compositional alterations that are unique to centenarians.
We observed expected shifts in the composition of centenarians' PBMCs from non-cytotoxic (e.g., naive CD4+ T cells and memory CD4+ T cells) to cytotoxic lymphocytes (e.g., cytotoxic CD4+ T cells) that have been observed previously in studies of human longevity. Similarly, the decrease of naive B cells with aging and longevity has also been reported previously. However, we also discovered novel compositional patterns of extreme old age including aging-related changes (e.g. a significant increase of CD14+ monocytes in older age that continues in the centenarian group), centenarian-specific changes (e.g. myeloid dendritic cells and plasmacytoid dendritic cells display no significant change among the three younger age groups but a unique, significant decrease occurs in extreme longevity), and aging-specific changes independent of extreme longevity (e.g. a significant increase of CD16+ monocytes in older age that then decreases in the centenarian age group).
The extent to which these unique patterns in centenarians are the drivers of extreme longevity or just the consequence of having reached an extreme old age remains an open question, since not everything we see in centenarians is necessarily important to reach extreme old ages. Additional data are needed to understand the effect of these patterns on human longevity. Overall, these findings display age-related changes in composition and transcription in both lymphocyte and myeloid cell types that collectively reflect immunocompetent profiles that may in part account for centenarians' ability to reach extreme ages.