The following articles have been published based on the results of Longitudinal Multi-Omic Study of Aging Determinants:

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 Tsurinov, Roman Chernyatchik, Vishwa Deep Dixit, Marko Jovanovic, Sheila A. Stewart, Mark J. Daly, Sergey Dmitriev, Eugene M. Oltz & Maxim N. Artyomov

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… READ MORE

Amanda Swain, Ekaterina Esaulova, Simone Brioschi, Irina Shchukina, Martina Kerndl, Monika Bambouskova, Zhangting Yao, Anwesha Laha, Konstantin Zaitsev, Samantha Burdess, Susan Gillfilan, Sheila A. Stewart, Marco Colonna, Maxim N. Artyomov

Systematic understanding of immune aging on a whole-body scale is currently lacking. We characterized age-associated alterations in immune cells across multiple mouse organs using single-cell RNA and antigen receptor sequencing and flow cytometry-based validation. We defined organ-specific and common immune alterations and identified a subpopulation of age-associated granzyme K (GZMK)-expressing CD8+ T (Taa) cells that are distinct from T effector memory (Tem) cells. Taa cells were highly clonal, had specific epigenetic and transcriptional signatures, developed in response to an aged host environment, and expressed markers of exhaustion and tissue homing. Activated Taa cells were the primary source of GZMK, which enhanced inflammatory functions of non-immune cells. In humans, proportions of the circulating GZMK+CD8+ T cell population that shares transcriptional and epigenetic signatures with mouse Taa cells increased during healthy aging. These results identify GZMK+ Taa cells as a potential target to address age-associated dysfunctions of the immune system. READ MORE