A new gene set identifies senescent cells and predicts senescence-associated pathways across tissues

Saul D, Kosinsky RL, Atkinson EJ, Doolittle ML, Zhang X, LeBrasseur NK, Pignolo RJ, Robbins PD, Niedernhofer LJ, Ikeno Y, Jurk D, Passos JF, Hickson LJ, Xue A, Monroe DG, Tchkonia T, Kirkland JL, Farr JN, Khosla S

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Abstract

Although cellular senescence drives multiple age-related co-morbidities through the senescence-associated secretory phenotype, in vivo senescent cell identification remains challenging. Here, we generate a gene set (SenMayo) and validate its enrichment in bone biopsies from two aged human cohorts. We further demonstrate reductions in SenMayo in bone following genetic clearance of senescent cells in mice and in adipose tissue from humans following pharmacological senescent cell clearance. We next use SenMayo to identify senescent hematopoietic or mesenchymal cells at the single cell level from human and murine bone marrow/bone scRNA-seq data. Thus, SenMayo identifies senescent cells across tissues and species with high fidelity. Using this senescence panel, we are able to characterize senescent cells at the single cell level and identify key intercellular signaling pathways. SenMayo also represents a potentially clinically applicable panel for monitoring senescent cell burden with aging and other conditions as well as in studies of senolytic drugs.

Abstract of "A new gene set identifies senescent cells and predicts senescence-associated pathways across tissues" by Saul D, Kosinsky RL, Atkinson EJ et al., https://doi.org/10.1038/s41467-022-32552-1, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.

Record

Archive ID
doi:10.1038/s41467-022-32552-1
Published
Aug 16, 2022
Venue
Nature communications
DOI
10.1038/s41467-022-32552-1
PubMed
35974106
PMC
PMC9381717
License
CC-BY
Provenance
europepmc

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