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SenNet recommendations for detecting senescent cells in different tissues

Abstract

Once considered a tissue culture-specific phenomenon, cellular senescence has now been linked to various biological processes with both beneficial and detrimental roles in humans, rodents and other species. Much of our understanding of senescent cell biology still originates from tissue culture studies, where each cell in the culture is driven to an irreversible cell cycle arrest. By contrast, in tissues, these cells are relatively rare and difficult to characterize, and it is now established that fully differentiated, postmitotic cells can also acquire a senescence phenotype. The SenNet Biomarkers Working Group was formed to provide recommendations for the use of cellular senescence markers to identify and characterize senescent cells in tissues. Here, we provide recommendations for detecting senescent cells in different tissues based on a comprehensive analysis of existing literature reporting senescence markers in 14 tissues in mice and humans. We discuss some of the recent advances in detecting and characterizing cellular senescence, including molecular senescence signatures and morphological features, and the use of circulating markers. We aim for this work to be a valuable resource for both seasoned investigators in senescence-related studies and newcomers to the field.

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Fig. 1: The hallmarks of cellular senescence.

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Acknowledgements

The National Institutes of Health (NIH) Cellular Senescence Network (SenNet) Consortium mourns the loss of J. Campisi, who passed away unexpectedly in January 2024. Judy always enjoyed her science and her interactions with her mentees, collaborators and colleagues. She would actively participate in all our meetings and contribute with her innovative and creative scientific ideas. Over the past 40 years of Judy’s scientific career, she pioneered research related to cellular senescence and cell fate. Judy truly recognized the relevance of senescence in fundamental aspects of ageing and age-related disease, with a major focus of investigating senescent cells both in model organisms and in humans. With our work in the SenNet Consortium, we hope to take forward her legacy of advancing cellular senescence research and eventually improving human health. The authors thank A. Roy for providing valuable suggestions during the manuscript’s preparation. The manuscript was supported by the following grants: UG3CA268202 (N.N., A. Rocha), R01AG050582 (N.N.), F31AG072748 (A. Rocha), T32GM136566 (A.A.), 1RM1HG011014-01 (S.V.), 1U54AG076040-01 (S.V.), 1U54AG079758-01 (M.G.T., P.D.A., Q.Z., S.Y.), 23CDA1056892 (S. Suvakov), Hevloution/AFAR (D.J.), R01AG68048 (J.F.P.), R01AG82708 (J.F.P.), AG068182 (D.J.), UG3CA268103 (J.F.P.), P01 AG062413 (S. Khosla, J.F.P.), P30AG067988 (G.A.K.), R01 AG069819 (D.A.B.), R01 AG076515 (S. Khosla), R33AG061456 (G.A.K.), U19AI089992 (R.R.M.), U24CA268108 (E.M.Q., J.C.S.), U54AG075931-01 (I.R.), U54AG079754 (D.A.B., M.J.S.), U54AG075931 (I.R.), U54AG075932 (B. Soygur, B. Schilling, F.E.D., J.C.), U54AG075934 (A.K., F. Chen, J.W., L.D., L.R., Y. Song), U54AG075941 (G.A.K.), U54AG075941-02 (P.R., R.R.), U54AG076040 (A.D.H., H.P., N. Sloan, O.K., R.P.-L., V.M., Y. Suh), U54AG076041 (L.J.N., E.L.S.), U54AG079753-01 (P.R., R.R.), U54AG079754 (M.J.S.), U54AG079759 (R.R.M.), U54AG079779 (D.J.B., M.J.S., N.B.), U54AG75941 (C.A.-M., E.A.L.E., K.I., P.C., S.S.), UG3CA268096 (R.D., S. Kong), UG3CA268105 (F.E.D.), UG3CA268112 (H.E.D.-L.), UG3CA268117 (N. Slavov, Z.D.), UG3CA275669 (C.M.C., M.J.S., P.T.G.) and UG3CA275686 (A.P., P.V., R.P.-L.).

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