Age‐associated expression of p21and p53 during human wound healing

• Published in: Aging cell Vol. 20; no. 5; pp. e13354 - n/a
• Main Authors: Chia, Chee W., Sherman‐Baust, Cheryl A., Larson, Sara A., Pandey, Ritu, Withers, Roxanne, Karikkineth, Ajoy C., Zukley, Linda M., Campisi, Judith, Egan, Josephine M., Sen, Ranjan, Ferrucci, Luigi
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.05.2021; Anatomical Society - Wiley; John Wiley and Sons Inc
• Subjects: Adult; Age; Aged; aging; Aging - metabolism; BASIC BIOLOGICAL SCIENCES; Biomarkers; Biopsy; Care and treatment; Conflicts of interest; Cyclin-Dependent Kinase Inhibitor p16 - metabolism; Cyclin-dependent kinase inhibitor p21; Cyclin-Dependent Kinase Inhibitor p21 - genetics; Cyclin-Dependent Kinase Inhibitor p21 - metabolism; Dipeptidyl-peptidase IV; Female; Fibroblasts; Gelatinase B; human wound healing; Humans; Immunohistochemistry; Male; Metalloproteinase; Older people; p21; p53; Peptidase; Phenotypes; Pilot Projects; Proteins; RNA; Senescence; Short Take; Skin - metabolism; Tumor proteins; Tumor Suppressor Protein p53 - metabolism; Women; Wound Healing; Wounds and injuries; β-Galactosidase; aging; human wound healing; p21; p53
• ISSN: 1474-9718; 1474-9726; 1474-9726
• DOI: 10.1111/acel.13354

In mice, cellular senescence and senescence‐associated secretory phenotype (SASP) positively contribute to cutaneous wound healing. In this proof‐of‐concept study, we investigated the expressions of p16, p21, and other senescence‐associated biomarkers during human wound healing in 24 healthy subjects using a double‐biopsy experimental design. The first punch biopsy created the wound and established the baseline. The second biopsy, concentric to the first and taken several days after wounding, was used to probe for expression of biomarkers by immunohistochemistry and RNA FISH. To assess the effects of age, we recruited 12 sex‐matched younger (30.2 ± 1.3 years) and 12 sex‐matched older (75.6 ± 1.8 years) subjects. We found that p21 and p53, but not p16, were induced during healing in younger, but not older subjects. A role for Notch signaling in p21 expression was inferred from the inducible activation of HES1. Further, other SASP biomarkers such as dipeptidyl peptidase‐4 (DPP4) were significantly induced upon wounding in both younger and older groups, whereas matrix metallopeptidase 9 (MMP9) was induced only in the younger group. Senescence‐associated β‐galactosidase (SA‐β‐gal) was not detectable before or after wounding. This pilot study suggests the possibility that human cutaneous wound healing is characterized by differential expression of p21 and p53 between younger and older subjects. Wound healing in humans is characterized by significant induction of p21‐ and p53‐positive cells but not p16‐positive cells in younger individuals. Furthermore, DPP4, a SASP biomarker, was significantly induced on wounding in both younger and older individuals, whereas MMP9 was induced only in younger individuals.