SenNet recommendations for detecting senescent cells in different tissues

Vidyani Suryadevara¹, Adam D Hudgins², Adarsh Rajesh³, Alberto Pappalardo⁴, Alla Karpova⁵, Amit K Dey⁶, Ann Hertzel^{7

8}, Anthony Agudelo^{9

10}, Azucena Rocha^{9

10}, Bikem Soygur¹¹, Birgit Schilling¹¹, Chase M Carver^{12

13}, Cristina Aguayo-Mazzucato¹⁴, Darren J Baker^{13

15}, David A Bernlohr^{7

8}, Diana Jurk^{12

13

16}, Dilyana B Mangarova¹, Ellen M Quardokus¹⁷, Elizabeth Ann L Enninga¹⁸, Elizabeth L Schmidt^{7

8}, Feng Chen⁵, Francesca E Duncan^{11

19}, Francesco Cambuli²⁰, Gagandeep Kaur²¹, George A Kuchel^{22

23}, Gung Lee^{12

13}, Heike E Daldrup-Link¹, Helene Martini^{12

13}, Hemali Phatnani^{20

24}, Iman M Al-Naggar²², Irfan Rahman²¹, Jia Nie²⁵, João F Passos^{12

13}, Jonathan C Silverstein²⁶, Judith Campisi¹¹, Julia Wang⁵, Kanako Iwasaki¹⁴, Karina Barbosa³, Kay Metis²⁶, Kerem Nernekli¹, Laura J Niedernhofer^{7

8}, Li Ding⁵, Lichao Wang^{22

23}, Lisa C Adams¹, Liu Ruiyang⁵, Madison L Doolittle^{12

13

27}, Marcos G Teneche³, Marissa J Schafer^{12

13

16}, Ming Xu^{22

23}, Mohammadjavad Hajipour¹, Mozhgan Boroumand⁶, Nathan Basisty⁶, Nicholas Sloan²⁸, Nikolai Slavov^{10

29

30

31}, Olena Kuksenko²⁸, Paul Robson^{32

33}, Paul T Gomez^{12

13}, Periklis Vasilikos³⁴, Peter D Adams³, Priscila Carapeto¹⁴, Quan Zhu³⁵, Ramalakshmi Ramasamy³², Rolando Perez-Lorenzo⁴, Rong Fan³⁶, Runze Dong^{37

38}, Ruth R Montgomery³⁶, Sadiya Shaikh²¹, Sanja Vickovic^{20

39

40

41}, Shanshan Yin³, Shoukai Kang³⁷, Sonja Suvakov^{12

42}, Sundeep Khosla^{12

13

27}, Vesna D Garovic^{18

42}, Vilas Menon^{24

43}, Yanxin Xu^{44

45

46}, Yizhe Song⁵, Yousin Suh^{2

34}, Zhixun Dou^{44

45

46}, Nicola Neretti^{47

48}

Affiliations

¹ Department of Radiology, Molecular Imaging Program at Stanford (MIPS), Stanford University, School of Medicine, Stanford, CA, USA.
² Department of Obstetrics and Gynecology, Columbia University, New York, NY, USA.
³ Sanford Burnham Prebys Medical Discovery Institute, Cancer Genome and Epigenetics Program, La Jolla, CA, USA.
⁴ Department of Dermatology, Columbia University, New York, NY, USA.
⁵ Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
⁶ National Institute on Aging, NIH, Baltimore, MD, USA.
⁷ Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN, USA.
⁸ Institute on the Biology of Aging and Metabolism, University of Minnesota, Minneapolis, MN, USA.
⁹ Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, RI, USA.
¹⁰ Center on the Biology of Aging, Brown University, Providence, RI, USA.
¹¹ The Buck Institute for Research on Aging, Novato, CA, USA.
¹² Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, USA.
¹³ Robert and Arlene Kogod Center on Aging, Rochester, MN, USA.
¹⁴ Islet Cell Biology and Regenerative Medicine, Joslin Diabetes Center, Harvard Medical School, Boston, USA.
¹⁵ Department of Biochemistry and Molecular Biology, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN, USA.
¹⁶ Department of Neurology, Mayo Clinic, Rochester, MN, USA.
¹⁷ Department of Intelligent Systems Engineering, Indiana University, Bloomington, IN, USA.
¹⁸ Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, MN, USA.
¹⁹ Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
²⁰ New York Genome Center, New York, NY, USA.
²¹ Department of Environmental Medicine, University of Rochester Medical Center, Rochester, NY, USA.
²² UConn Center on Aging, University of Connecticut Health Center, Farmington, CT, USA.
²³ Department of Genetics and Genome Sciences, University of Connecticut Health Center, Farmington, CT, USA.
²⁴ Department of Neurology, Columbia University Irving Medical Center, New York, NY, USA.
²⁵ Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
²⁶ Department of Biomedical Informatics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
²⁷ Division of Endocrinology, Diabetes and Metabolism, Mayo Clinic, Rochester, MN, USA.
²⁸ Department of Neurology, Columbia University Medical Center, New York, NY, USA.
²⁹ Department of Bioengineering, Northeastern University, Boston, MA, USA.
³⁰ Department of Biology, Northeastern University, Boston, MA, USA.
³¹ Barnett Institute for Chemical and Biological Analysis, Northeastern University, Boston, MA, USA.
³² The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
³³ Institute for Systems Genomics, University of Connecticut, Farmington, CT, USA.
³⁴ Department of Genetics and Development, Columbia University, New York, NY, USA.
³⁵ Center for Epigenomics, University of California, San Diego, CA, USA.
³⁶ Yale-Center for Research on Aging, Yale School of Medicine, New Haven, CT, USA.
³⁷ Department of Biochemistry, University of Washington, Seattle, WA, USA.
³⁸ Graduate Program in Biological Physics, Structure and Design, University of Washington, Seattle, WA, USA.
³⁹ Herbert Irving Institute for Cancer Dynamics, Columbia University, New York, NY, USA.
⁴⁰ Department of Biomedical Engineering, Columbia University, New York, NY, USA.
⁴¹ Science for Life Laboratory, Department of Immunology, Genetics and Pathology, Beijer Laboratory for Gene and Neuro Research, Uppsala University, Uppsala, Sweden.
⁴² Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA.
⁴³ Center for Translational and Computational Neuroimmunology, Columbia University Irving Medical Center, New York, NY, USA.
⁴⁴ Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, USA.
⁴⁵ Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA.
⁴⁶ Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
⁴⁷ Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, RI, USA. nicola_neretti@brown.edu.
⁴⁸ Center on the Biology of Aging, Brown University, Providence, RI, USA. nicola_neretti@brown.edu.

PMID: 38831121
PMCID: PMC11578798 (available on 2025-12-01)
DOI: 10.1038/s41580-024-00738-8

Review

SenNet recommendations for detecting senescent cells in different tissues

Vidyani Suryadevara et al. Nat Rev Mol Cell Biol. 2024 Dec.

. 2024 Dec;25(12):1001-1023.

doi: 10.1038/s41580-024-00738-8. Epub 2024 Jun 3.

Authors

Affiliations

¹ Department of Radiology, Molecular Imaging Program at Stanford (MIPS), Stanford University, School of Medicine, Stanford, CA, USA.
² Department of Obstetrics and Gynecology, Columbia University, New York, NY, USA.
³ Sanford Burnham Prebys Medical Discovery Institute, Cancer Genome and Epigenetics Program, La Jolla, CA, USA.
⁴ Department of Dermatology, Columbia University, New York, NY, USA.
⁵ Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
⁶ National Institute on Aging, NIH, Baltimore, MD, USA.
⁷ Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN, USA.
⁸ Institute on the Biology of Aging and Metabolism, University of Minnesota, Minneapolis, MN, USA.
⁹ Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, RI, USA.
¹⁰ Center on the Biology of Aging, Brown University, Providence, RI, USA.
¹¹ The Buck Institute for Research on Aging, Novato, CA, USA.
¹² Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, USA.
¹³ Robert and Arlene Kogod Center on Aging, Rochester, MN, USA.
¹⁴ Islet Cell Biology and Regenerative Medicine, Joslin Diabetes Center, Harvard Medical School, Boston, USA.
¹⁵ Department of Biochemistry and Molecular Biology, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN, USA.
¹⁶ Department of Neurology, Mayo Clinic, Rochester, MN, USA.
¹⁷ Department of Intelligent Systems Engineering, Indiana University, Bloomington, IN, USA.
¹⁸ Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, MN, USA.
¹⁹ Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
²⁰ New York Genome Center, New York, NY, USA.
²¹ Department of Environmental Medicine, University of Rochester Medical Center, Rochester, NY, USA.
²² UConn Center on Aging, University of Connecticut Health Center, Farmington, CT, USA.
²³ Department of Genetics and Genome Sciences, University of Connecticut Health Center, Farmington, CT, USA.
²⁴ Department of Neurology, Columbia University Irving Medical Center, New York, NY, USA.
²⁵ Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
²⁶ Department of Biomedical Informatics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
²⁷ Division of Endocrinology, Diabetes and Metabolism, Mayo Clinic, Rochester, MN, USA.
²⁸ Department of Neurology, Columbia University Medical Center, New York, NY, USA.
²⁹ Department of Bioengineering, Northeastern University, Boston, MA, USA.
³⁰ Department of Biology, Northeastern University, Boston, MA, USA.
³¹ Barnett Institute for Chemical and Biological Analysis, Northeastern University, Boston, MA, USA.
³² The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
³³ Institute for Systems Genomics, University of Connecticut, Farmington, CT, USA.
³⁴ Department of Genetics and Development, Columbia University, New York, NY, USA.
³⁵ Center for Epigenomics, University of California, San Diego, CA, USA.
³⁶ Yale-Center for Research on Aging, Yale School of Medicine, New Haven, CT, USA.
³⁷ Department of Biochemistry, University of Washington, Seattle, WA, USA.
³⁸ Graduate Program in Biological Physics, Structure and Design, University of Washington, Seattle, WA, USA.
³⁹ Herbert Irving Institute for Cancer Dynamics, Columbia University, New York, NY, USA.
⁴⁰ Department of Biomedical Engineering, Columbia University, New York, NY, USA.
⁴¹ Science for Life Laboratory, Department of Immunology, Genetics and Pathology, Beijer Laboratory for Gene and Neuro Research, Uppsala University, Uppsala, Sweden.
⁴² Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA.
⁴³ Center for Translational and Computational Neuroimmunology, Columbia University Irving Medical Center, New York, NY, USA.
⁴⁴ Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, USA.
⁴⁵ Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA.
⁴⁶ Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
⁴⁷ Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, RI, USA. nicola_neretti@brown.edu.
⁴⁸ Center on the Biology of Aging, Brown University, Providence, RI, USA. nicola_neretti@brown.edu.

PMID: 38831121
PMCID: PMC11578798 (available on 2025-12-01)
DOI: 10.1038/s41580-024-00738-8

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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Conflict of interest statement

Competing interests: The authors declare the following competing interests: J.C. is a founder and shareholder of Unity Biotechnology, which develops senolytic drugs. M.J.S., C.M.C. and Mayo Clinic have intellectual property related to this research. Research in the M.J.S. and D.J.B. laboratory is reviewed by the Mayo Clinic Conflict of Interest Review Board and conducted in compliance with Mayo Clinic Conflict of Interest policies. D.J.B. has a potential financial interest related to this research; he is a co-inventor on patents held by Mayo Clinic and patent applications licensed to or filed by Unity Biotechnology and a Unity Biotechnology shareholder. N. Slavov is a founding director and CEO of Parallel Squared Technology Institute, which is a non-profit research institute.

References

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SenNet recommendations for detecting senescent cells in different tissues

Affiliations

SenNet recommendations for detecting senescent cells in different tissues

Authors

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Abstract

Conflict of interest statement

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