Clearance of p21 highly expressing senescent cells accelerates cutaneous wound healing

Nathan S Gasek; Pengyi Yan; Junyu Zhu; K-Raman Purushothaman; Taewan Kim; Lichao Wang; Binsheng Wang; William F Flynn; Mingda Sun; Chun Guo; Billy Huggins; Roshanak Sharafieh; Yueying Zhou; Vojtech Parizek; Tamar Tchkonia; James L Kirkland; Saranya P Wyles; Ming Xu

doi:10.1038/s43587-024-00755-4

Clearance of p21 highly expressing senescent cells accelerates cutaneous wound healing

Nat Aging. 2024 Nov 13. doi: 10.1038/s43587-024-00755-4. Online ahead of print.

Authors

Nathan S Gasek^#^{1

2}, Pengyi Yan^#^{1

2}, Junyu Zhu^#^{1

2}, K-Raman Purushothaman³, Taewan Kim^{1

2}, Lichao Wang^{1

2}, Binsheng Wang^{1

2}, William F Flynn⁴, Mingda Sun¹, Chun Guo¹, Billy Huggins^{1

2}, Roshanak Sharafieh⁵, Yueying Zhou^{1

6}, Vojtech Parizek¹, Tamar Tchkonia^{7

8}, James L Kirkland^{7

8

9}, Saranya P Wyles³, Ming Xu^{10

11}

Affiliations

¹ UConn Center on Aging, UConn Health, Farmington, CT, USA.
² Department of Genetics and Genome Sciences, UConn Health, Farmington, CT, USA.
³ Department of Dermatology, Mayo Clinic, Rochester, MN, USA.
⁴ The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
⁵ Department of Surgery, UConn Health, Farmington, CT, USA.
⁶ Xiangya Stomatological Hospital, Central South University, Changsha, China.
⁷ Division of Endocrinology, Diabetes and Metabolism, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
⁸ Center for Advanced Gerotherapeutics, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
⁹ Division of General Internal Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
¹⁰ UConn Center on Aging, UConn Health, Farmington, CT, USA. mixu@uchc.edu.
¹¹ Department of Genetics and Genome Sciences, UConn Health, Farmington, CT, USA. mixu@uchc.edu.

^# Contributed equally.

PMID: 39537987
DOI: 10.1038/s43587-024-00755-4

Abstract

While senescent cells have detrimental roles in several contexts, they are highly heterogeneous. p16 highly expressing senescent cells have been reported to exert beneficial functions in wound healing. Here we use Xenium spatial transcriptomics to identify a distinct p21 highly expressing senescent population induced on wounding, with a pro-inflammatory profile. We find that clearing p21 highly expressing cells expedites wound closure and is partially mediated by NF-κB inhibition, thus enhancing our understanding of the multifaceted functions of senescence in tissue remodeling.

Abstract

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