| First Author | Rübe CE | Year | 2021 |
| Journal | NPJ Aging Mech Dis | Volume | 7 |
| Issue | 1 | Pages | 7 |
| PubMed ID | 33795696 | Mgi Jnum | J:343536 |
| Mgi Id | MGI:6764961 | Doi | 10.1038/s41514-021-00060-z |
| Citation | Rube CE, et al. (2021) Human skin aging is associated with increased expression of the histone variant H2A.J in the epidermis. NPJ Aging Mech Dis 7(1):7 |
| abstractText | Cellular senescence is an irreversible growth arrest that occurs as a result of damaging stimuli, including DNA damage and/or telomere shortening. Here, we investigate histone variant H2A.J as a new biomarker to detect senescent cells during human skin aging. Skin biopsies from healthy volunteers of different ages (18-90 years) were analyzed for H2A.J expression and other parameters involved in triggering and/or maintaining cellular senescence. In the epidermis, the proportions of H2A.J-expressing keratinocytes increased from approximately 20% in young to approximately 60% in aged skin. Inverse correlations between Ki67- and H2A.J staining in germinative layers may reflect that H2A.J-expressing cells having lost their capacity to divide. As cellular senescence is triggered by DNA-damage signals, persistent 53BP1-foci, telomere lengths, and telomere-associated damage foci were analyzed in epidermal keratinocytes. Only slight age-related telomere attrition and few persistent nuclear 53BP1-foci, occasionally colocalizing with telomeres, suggest that unprotected telomeres are not a significant cause of senescence during skin aging. Quantification of integrin-alpha6+ basal cells suggests that the number and function of stem/progenitor cells decreased during aging and their altered proliferation capacities resulted in diminished tissue renewal with epidermal thinning. Collectively, our findings suggest that H2A.J is a sensitive marker of epidermal aging in human skin. |
