Yasufumi Tomioka, Koji Kitazawa, Kohsaku Numa, Jun-Wei B Hughes, Norihiko Yokoi, Chie Sotozono
{"title":"老年人结膜上皮细胞中存在衰老细胞。","authors":"Yasufumi Tomioka, Koji Kitazawa, Kohsaku Numa, Jun-Wei B Hughes, Norihiko Yokoi, Chie Sotozono","doi":"10.1007/s10384-023-01047-x","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>The ocular surface microenvironment changes with aging. However, it remains unclear if cellular senescence influences the ocular surface. We investigated the presence of p16<sup>INK4a</sup>-expressing senescent cells in healthy human conjunctiva.</p><p><strong>Study design: </strong>Clinical and experimental.</p><p><strong>Methods: </strong>Healthy conjunctival tissue samples were obtained from middle-aged and elderly subjects. RT-qPCR was performed to assess the expression of senescence markers CDKN2A (p16<sup>INK4a</sup>) and CDKN1A (p21<sup>CIP1/WAF1</sup>) and immunostaining was performed to examine the expression of the senescence marker p16<sup>INK4a</sup>, stem cell markers Ki67 and p63, tight-junction marker ZO-1.</p><p><strong>Results: </strong>Our study involved 19 conjunctival tissue samples (10 elderly and 9 middle-aged), mean age [elderly: 75.8 ± 3.7 years (72-81), middle-aged: 52.7 ± 7 years (38-59)], sex (elderly: 3 men, 7 women; middle-aged: 3 men, 6 women). The expression of p16<sup>INK4a</sup> was significantly increased at the RNA level in the elderly compared to middle-aged (p < 0.05). Positivity rate of p16<sup>INK4a</sup> was significantly elevated in the elderly (15.0 ± 7.8%) compared to middle-aged (0.2 ± 0.6%) (p < 0.05). Positivity rate of Ki67and p63 was significantly reduced in the elderly (1.7 ± 1.7% and 16.5 ± 9.5%) compared to middle-aged (3.9 ± 1.8% and 24.7 ± 5.7%) (p < 0.05). ZO-1 expression was reduced in tissue samples showing p16<sup>INK4a</sup>-positivity but retained in tissue samples in which p16<sup>INK4a</sup> was undetectable.</p><p><strong>Conclusions: </strong>Senescent cells accumulate with age in the conjunctival epithelium, accompanied by a decrease in Ki67, p63 and ZO-1 expressing cells.</p>","PeriodicalId":14563,"journal":{"name":"Japanese Journal of Ophthalmology","volume":null,"pages":null},"PeriodicalIF":2.1000,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The existence of senescent cells in conjunctival epithelium from elderly individuals.\",\"authors\":\"Yasufumi Tomioka, Koji Kitazawa, Kohsaku Numa, Jun-Wei B Hughes, Norihiko Yokoi, Chie Sotozono\",\"doi\":\"10.1007/s10384-023-01047-x\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>The ocular surface microenvironment changes with aging. However, it remains unclear if cellular senescence influences the ocular surface. We investigated the presence of p16<sup>INK4a</sup>-expressing senescent cells in healthy human conjunctiva.</p><p><strong>Study design: </strong>Clinical and experimental.</p><p><strong>Methods: </strong>Healthy conjunctival tissue samples were obtained from middle-aged and elderly subjects. RT-qPCR was performed to assess the expression of senescence markers CDKN2A (p16<sup>INK4a</sup>) and CDKN1A (p21<sup>CIP1/WAF1</sup>) and immunostaining was performed to examine the expression of the senescence marker p16<sup>INK4a</sup>, stem cell markers Ki67 and p63, tight-junction marker ZO-1.</p><p><strong>Results: </strong>Our study involved 19 conjunctival tissue samples (10 elderly and 9 middle-aged), mean age [elderly: 75.8 ± 3.7 years (72-81), middle-aged: 52.7 ± 7 years (38-59)], sex (elderly: 3 men, 7 women; middle-aged: 3 men, 6 women). The expression of p16<sup>INK4a</sup> was significantly increased at the RNA level in the elderly compared to middle-aged (p < 0.05). Positivity rate of p16<sup>INK4a</sup> was significantly elevated in the elderly (15.0 ± 7.8%) compared to middle-aged (0.2 ± 0.6%) (p < 0.05). Positivity rate of Ki67and p63 was significantly reduced in the elderly (1.7 ± 1.7% and 16.5 ± 9.5%) compared to middle-aged (3.9 ± 1.8% and 24.7 ± 5.7%) (p < 0.05). ZO-1 expression was reduced in tissue samples showing p16<sup>INK4a</sup>-positivity but retained in tissue samples in which p16<sup>INK4a</sup> was undetectable.</p><p><strong>Conclusions: </strong>Senescent cells accumulate with age in the conjunctival epithelium, accompanied by a decrease in Ki67, p63 and ZO-1 expressing cells.</p>\",\"PeriodicalId\":14563,\"journal\":{\"name\":\"Japanese Journal of Ophthalmology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.1000,\"publicationDate\":\"2024-03-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Japanese Journal of Ophthalmology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s10384-023-01047-x\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/2/5 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"OPHTHALMOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Japanese Journal of Ophthalmology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s10384-023-01047-x","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/2/5 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"OPHTHALMOLOGY","Score":null,"Total":0}
The existence of senescent cells in conjunctival epithelium from elderly individuals.
Purpose: The ocular surface microenvironment changes with aging. However, it remains unclear if cellular senescence influences the ocular surface. We investigated the presence of p16INK4a-expressing senescent cells in healthy human conjunctiva.
Study design: Clinical and experimental.
Methods: Healthy conjunctival tissue samples were obtained from middle-aged and elderly subjects. RT-qPCR was performed to assess the expression of senescence markers CDKN2A (p16INK4a) and CDKN1A (p21CIP1/WAF1) and immunostaining was performed to examine the expression of the senescence marker p16INK4a, stem cell markers Ki67 and p63, tight-junction marker ZO-1.
Results: Our study involved 19 conjunctival tissue samples (10 elderly and 9 middle-aged), mean age [elderly: 75.8 ± 3.7 years (72-81), middle-aged: 52.7 ± 7 years (38-59)], sex (elderly: 3 men, 7 women; middle-aged: 3 men, 6 women). The expression of p16INK4a was significantly increased at the RNA level in the elderly compared to middle-aged (p < 0.05). Positivity rate of p16INK4a was significantly elevated in the elderly (15.0 ± 7.8%) compared to middle-aged (0.2 ± 0.6%) (p < 0.05). Positivity rate of Ki67and p63 was significantly reduced in the elderly (1.7 ± 1.7% and 16.5 ± 9.5%) compared to middle-aged (3.9 ± 1.8% and 24.7 ± 5.7%) (p < 0.05). ZO-1 expression was reduced in tissue samples showing p16INK4a-positivity but retained in tissue samples in which p16INK4a was undetectable.
Conclusions: Senescent cells accumulate with age in the conjunctival epithelium, accompanied by a decrease in Ki67, p63 and ZO-1 expressing cells.
期刊介绍：
The Japanese Journal of Ophthalmology (JJO) was inaugurated in 1957 as a quarterly journal published in English by the Ophthalmology Department of the University of Tokyo, with the aim of disseminating the achievements of Japanese ophthalmologists worldwide. JJO remains the only Japanese ophthalmology journal published in English. In 1997, the Japanese Ophthalmological Society assumed the responsibility for publishing the Japanese Journal of Ophthalmology as its official English-language publication.
Currently the journal is published bimonthly and accepts papers from authors worldwide. JJO has become an international interdisciplinary forum for the publication of basic science and clinical research papers.
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