Biological aging of different blood cell types

Abstract Biological age (BA) captures detrimental age-related changes. The best-known and most-used BA indicators include DNA methylation–based epigenetic clocks and telomere length (TL). The most common biological sample material for epidemiological aging studies, whole blood, is composed of different cell types. We aimed to compare differences in BAs between blood cell types and assessed the BA indicators’ cell type-specific associations with chronological age (CA). An analysis of DNA methylation–based BA indicators, including TL, methylation level at cg16867657 in ELOVL2 , as well as the Hannum, Horvath, DNAmPhenoAge, and DunedinPACE epigenetic clocks, was performed on 428 biological samples of 12 blood cell types. BA values were different in the majority of the pairwise comparisons between cell types, as well as in comparison to whole blood ( p < 0.05). DNAmPhenoAge showed the largest cell type differences, up to 44.5 years and DNA methylation-based TL showed the lowest differences. T cells generally had the "youngest" BA values, with differences across subsets, whereas monocytes had the "oldest" values. All BA indicators, except DunedinPACE, strongly correlated with CA within a cell type. Some differences such as DNAmPhenoAge-difference between naïve CD4 + T cells and monocytes were constant regardless of the blood donor's CA (range 20–80 years), while for DunedinPACE they were not. In conclusion, DNA methylation–based indicators of BA exhibit cell type–specific characteristics. Our results have implications for understanding the molecular mechanisms underlying epigenetic clocks and underscore the importance of considering cell composition when utilizing them as indicators for the success of aging interventions.