Age-related changes in immune cell composition and functionality are associated with multimorbidity
and mortality. However, many centenarians delay the onset of aging-related disease suggesting the presence of elite
immunity that remains highly functional at extreme old age.
To identify immune-specific patterns of aging and extreme human longevity, we analyzed novel single cell
profiles from the peripheral blood mononuclear cells (PBMCs) of a random sample of 7 centenarians (mean age 106)
and publicly available single cell RNA-sequencing (scRNA-seq) datasets that included an additional 7 centenarians as
well as 52 people at younger ages (20–89 years).
The analysis confirmed known shifts in the ratio of lymphocytes to myeloid cells, and noncytotoxic to
cytotoxic cell distributions with aging, but also identified significant shifts from CD4+ T cell to B cell populations in
centenarians suggesting a history of exposure to natural and environmental immunogens. We validated several of
these findings using flow cytometry analysis of the same samples. Our transcriptional analysis identified cell type
signatures specific to exceptional longevity that included genes with age-related changes (e.g., increased expression of
STK17A, a gene known to be involved in DNA damage response) as well as genes expressed uniquely in centenarians’
PBMCs (e.g., S100A4, part of the S100 protein family studied in age-related disease and connected to longevity and
Collectively, these data suggest that centenarians harbor unique, highly functional immune systems
that have successfully adapted to a history of insults allowing for the achievement of exceptional longevity.