Enhanced epigenetic profiling of classical human monocytes reveals a specific signature of healthy aging in the DNA methylome

Irina Shchukina, Juhi Bagaitkar, Oleg Shpynov, Ekaterina Loginicheva, Sofia Porter, Denis A. Mogilenko, Erica Wolin, Patrick Collins, German Demidov, Mykyta Artomov, Konstantin Zaitsev, Sviatoslav Sidorov, Christina Camell, Monika Bambouskova, Laura Arthur, Amanda Swain, Alexandra Panteleeva, Aleksei Dievskii, Evgeny Kurbatsky, Petr TsurinovRoman Chernyatchik, Vishwa Deep Dixit, Marko Jovanovic, Sheila A. Stewart, Mark J. Daly, Sergey Dmitriev, Gene Oltz, Maxim N. Artyomov

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

The impact of healthy aging on molecular programming of immune cells is poorly understood. Here we report comprehensive characterization of healthy aging in human classical monocytes, with a focus on epigenomic, transcriptomic and proteomic alterations, as well as the corresponding proteomic and metabolomic data for plasma, using healthy cohorts of 20 young and 20 older males (~27 and ~64 years old on average). For each individual, we performed enhanced reduced representation bisulfite sequencing-based DNA methylation profiling, which allowed us to identify a set of age-associated differentially methylated regions (DMRs)—a novel, cell-type-specific signature of aging in the DNA methylome. Hypermethylation events were associated with H3K27me3 in the CpG islands near promoters of lowly expressed genes, while hypomethylated DMRs were enriched in H3K4me1-marked regions and associated with age-related increase of expression of the corresponding genes, providing a link between DNA methylation and age-associated transcriptional changes in primary human cells.

Original languageEnglish
Pages (from-to)124-141
Number of pages18
JournalNature Aging
Volume1
Issue number1
DOIs
StatePublished - Jan 2021

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