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

Dominik Saul, Robyn Laura Kosinsky, Elizabeth J. Atkinson, Madison L. Doolittle, Xu Zhang, Nathan K. LeBrasseur, Robert J. Pignolo, Paul D. Robbins, Laura J. Niedernhofer, Yuji Ikeno, Diana Jurk, João F. Passos, La Tonya J. Hickson, Ailing Xue, David G. Monroe, Tamara Tchkonia, James L. Kirkland, Joshua N. Farr, Sundeep Khosla

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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.

Original languageEnglish (US)
Article number4827
JournalNature communications
Volume13
Issue number1
DOIs
StatePublished - Dec 2022

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • General
  • Physics and Astronomy(all)

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