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, LaTonya J. Hickson, Ailing Xue, David G. Monroe, Tamara Tchkonia, James L. Kirkland, Joshua N. Farr () and Sundeep Khosla ()
Additional contact information
Dominik Saul: Mayo Clinic
Robyn Laura Kosinsky: Mayo Clinic
Elizabeth J. Atkinson: Mayo Clinic
Madison L. Doolittle: Mayo Clinic
Xu Zhang: Mayo Clinic
Nathan K. LeBrasseur: Mayo Clinic
Robert J. Pignolo: Mayo Clinic
Paul D. Robbins: University of Minnesota
Laura J. Niedernhofer: University of Minnesota
Yuji Ikeno: University of Texas Health
Diana Jurk: Mayo Clinic
João F. Passos: Mayo Clinic
LaTonya J. Hickson: Mayo Clinic
Ailing Xue: Mayo Clinic
David G. Monroe: Mayo Clinic
Tamara Tchkonia: Mayo Clinic
James L. Kirkland: Mayo Clinic
Joshua N. Farr: Mayo Clinic
Sundeep Khosla: Mayo Clinic

Nature Communications, 2022, vol. 13, issue 1, 1-15

Abstract: 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.

Date: 2022
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32552-1

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DOI: 10.1038/s41467-022-32552-1

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