Identification of a new human senescent skin cell marker ribonucleoside-diphosphate reductase subunit M2 B

IF 4.4 4区 医学 Q1 GERIATRICS & GERONTOLOGY Biogerontology Pub Date : 2024-09-11 DOI:10.1007/s10522-024-10135-5
Kento Takaya, Kazuo Kishi
{"title":"Identification of a new human senescent skin cell marker ribonucleoside-diphosphate reductase subunit M2 B","authors":"Kento Takaya, Kazuo Kishi","doi":"10.1007/s10522-024-10135-5","DOIUrl":null,"url":null,"abstract":"<p>In skin aging, it has been hypothesized that aging fibroblasts accumulate within the epidermal basal layer, dermis, and subcutaneous fat, causing abnormal tissue remodeling and extracellular matrix dysfunction, thereby inducing an aging-related secretory phenotype (SASP). A new treatment for skin aging involves the specific elimination of senescent skin cells, especially fibroblasts within the dermis and keratinocytes in the basal layer. This requires the identification of specific protein markers of senescent cells, such as ribonucleoside-diphosphate reductase subunit M2 B (RRM2B), which is upregulated in various malignancies in response to DNA stress damage. However, the behavior and role of RRM2B in skin aging remain unclear. Therefore, we examined whether RRM2B functions as a senescence marker using a human dermal fibroblast model of aging. In a model of cellular senescence induced by replicative aging and exposure to ionizing radiation or UVB, RRM2B was upregulated at the gene and protein levels. This was correlated with decreased uptake of the senescence-associated β-galactosidase activity and proliferation marker bromodeoxyuridine. <i>RRM2B</i> upregulation was concurrent with the increased expression of SASP factor genes. Furthermore, using fluorescence flow cytometry, RRM2B-positive cells were recovered more frequently in the aging cell population. In aging human skin, RRM2B was also found to be more abundant in the dermis and epidermal basal layer than other proteins. Therefore, RRM2B may serve as a clinical marker to identify senescent skin cells.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"58 1","pages":""},"PeriodicalIF":4.4000,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biogerontology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s10522-024-10135-5","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GERIATRICS & GERONTOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

In skin aging, it has been hypothesized that aging fibroblasts accumulate within the epidermal basal layer, dermis, and subcutaneous fat, causing abnormal tissue remodeling and extracellular matrix dysfunction, thereby inducing an aging-related secretory phenotype (SASP). A new treatment for skin aging involves the specific elimination of senescent skin cells, especially fibroblasts within the dermis and keratinocytes in the basal layer. This requires the identification of specific protein markers of senescent cells, such as ribonucleoside-diphosphate reductase subunit M2 B (RRM2B), which is upregulated in various malignancies in response to DNA stress damage. However, the behavior and role of RRM2B in skin aging remain unclear. Therefore, we examined whether RRM2B functions as a senescence marker using a human dermal fibroblast model of aging. In a model of cellular senescence induced by replicative aging and exposure to ionizing radiation or UVB, RRM2B was upregulated at the gene and protein levels. This was correlated with decreased uptake of the senescence-associated β-galactosidase activity and proliferation marker bromodeoxyuridine. RRM2B upregulation was concurrent with the increased expression of SASP factor genes. Furthermore, using fluorescence flow cytometry, RRM2B-positive cells were recovered more frequently in the aging cell population. In aging human skin, RRM2B was also found to be more abundant in the dermis and epidermal basal layer than other proteins. Therefore, RRM2B may serve as a clinical marker to identify senescent skin cells.

Abstract Image

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
鉴定一种新的人类衰老皮肤细胞标记核糖核苷-二磷酸还原酶亚基 M2 B
据推测,在皮肤衰老过程中,衰老的成纤维细胞聚集在表皮基底层、真皮层和皮下脂肪中,导致组织重塑异常和细胞外基质功能失调,从而诱发与衰老相关的分泌表型(SASP)。治疗皮肤衰老的一种新方法是特异性消除衰老的皮肤细胞,尤其是真皮层的成纤维细胞和基底层的角质细胞。这需要识别衰老细胞的特定蛋白质标记,如核糖核苷-二磷酸还原酶亚基 M2 B(RRM2B),它在各种恶性肿瘤中因 DNA 应激损伤而上调。然而,RRM2B 在皮肤老化中的行为和作用仍不清楚。因此,我们利用人类真皮成纤维细胞衰老模型研究了 RRM2B 是否具有衰老标志物的功能。在由复制性衰老和暴露于电离辐射或紫外线诱导的细胞衰老模型中,RRM2B 在基因和蛋白质水平上被上调。这与衰老相关的β-半乳糖苷酶活性和增殖标志物溴脱氧尿苷的吸收减少有关。RRM2B 的上调与 SASP 因子基因表达的增加同时发生。此外,利用荧光流式细胞术,在衰老细胞群中更频繁地发现 RRM2B 阳性细胞。在衰老的人体皮肤中,RRM2B 在真皮层和表皮基底层的含量也高于其他蛋白质。因此,RRM2B 可作为识别衰老皮肤细胞的临床标志物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
Biogerontology
Biogerontology 医学-老年医学
CiteScore
8.00
自引率
4.40%
发文量
54
审稿时长
>12 weeks
期刊介绍: The journal Biogerontology offers a platform for research which aims primarily at achieving healthy old age accompanied by improved longevity. The focus is on efforts to understand, prevent, cure or minimize age-related impairments. Biogerontology provides a peer-reviewed forum for publishing original research data, new ideas and discussions on modulating the aging process by physical, chemical and biological means, including transgenic and knockout organisms; cell culture systems to develop new approaches and health care products for maintaining or recovering the lost biochemical functions; immunology, autoimmunity and infection in aging; vertebrates, invertebrates, micro-organisms and plants for experimental studies on genetic determinants of aging and longevity; biodemography and theoretical models linking aging and survival kinetics.
期刊最新文献
Investigating cognitive impairments and hippocampal proteome alterations in aged male rats with TAA-Induced minimal hepatic encephalopathy. Quercetin preserves mitochondria-endoplasmic reticulum contact sites improving mitochondrial dynamics in aged myocardial cells. 2,4-Dinitrophenol is toxic on a low caloric diet but extends lifespan of Drosophila melanogaster on nutrient-rich diets without an impact on metabolism. Ribose-induced advanced glycation end products reduce the lifespan in Drosophila melanogaster by changing the redox state and down-regulating the Sirtuin genes. Exercise, hormesis and ageing: a new section in Biogerontology.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1