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

Bibliographical note

Funding Information:
This work was supported by the German Research Foundation (D.F.G., 413501650) (D.S.), National Institutes of Health (NIH) grants P01 AG062413 (S.K., J.N.F., N.K.L., R.P., P.D.R., L.J.N., Y.I., J.P., D.G.M., T.T., J.L.K.), R01 AG076515 (S.K., D.G.M.), R21 AG065868 (S.K., J.N.F), K01 AR070241 (J.N.F.), R01 AG063707 (D.G.M.), R37 AG 013925 (J.L.K., T.T.), R33AG 61456 (J.L.K., T.T., R.P., P.D.R., L.J.N., S.K.), 1R01AG068048-01 (JFP), R56 AG 60907 and R01 AG55529 (N.K.L.)., the Connor Fund (J.L.K., T.T.), Robert P. and Arlene R. Kogod (J.L.K.), Robert J. and Theresa W. Ryan (J.L.K., T.T.), the Noaber Foundation (J.L.K., T.T.), and Mildred Scheel postdoc fellowship by the German Cancer Aid (R.L.K.). X.Z. is supported by the Robert and Arlene Kogod Center on Aging Career Development Award. The authors thank SA Johnsen and FH Hamdan for inspiring discussions.

Publisher Copyright:
© 2022, The Author(s).

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