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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 p16 INK4a -expressing senescent cells in healthy human conjunctiva. Study design Clinical and experimental. Methods Health...
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| Published in: | Japanese journal of ophthalmology 2024-03, Vol.68 (2), p.157-165 |
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| container_title | Japanese journal of ophthalmology |
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| creator | Tomioka, Yasufumi Kitazawa, Koji Numa, Kohsaku Hughes, Jun-Wei B. Yokoi, Norihiko Sotozono, Chie |
| description | Purpose
The ocular surface microenvironment changes with aging. However, it remains unclear if cellular senescence influences the ocular surface. We investigated the presence of p16
INK4a
-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 (p16
INK4a
)
and
CDKN1A (p21
CIP1/WAF1
)
and immunostaining was performed to examine the expression of the senescence marker p16
INK4a
, 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
p16
INK4a
was significantly increased at the RNA level in the elderly compared to middle-aged (
p
< 0.05). Positivity rate of p16
INK4a
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
INK4a
-positivity but retained in tissue samples in which p16
INK4a
was undetectable.
Conclusions
Senescent cells accumulate with age in the conjunctival epithelium, accompanied by a decrease in Ki67, p63 and ZO-1 expressing cells. |
| doi_str_mv | 10.1007/s10384-023-01047-x |
| format | article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_proquest_miscellaneous_2922450578</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2985944162</sourcerecordid><originalsourceid>FETCH-LOGICAL-p213t-e48c911ee22830f0c1ed4305a0f56e206ae5dca8867df564b39bb0829835b3ab3</originalsourceid><addsrcrecordid>eNpdkUtLw0AUhQdRbK3-ARcy4MZN9M4rmSyl-IKCm7oe8rixU5JJzCSl_fdObUVwdeDej8PhHEKuGdwzgOTBMxBaRsBFBAxkEm1PyJTFTEScy_iUTAE4ixRTakIuvF8DgOSCn5OJ0IKxWKdTslyukOLW-gFdgbStqEeHvkA30ALr2lPraNG69eiKwW6ymmJnhxXWdmxo1bcNxbrEvt4FrrQbW45Z7S_JWRUEr446Ix_PT8v5a7R4f3mbPy6ijjMxRCh1kTKGyLkWUEHBsJQCVAaVipFDnKEqi0zrOCnDReYizXPQPNVC5SLLxYzcHXy7vv0a0Q-msX6fOnPYjt7wNBShQCU6oLf_0HU79i6kC5RWqZQs5oG6OVJj3mBput42Wb8zv30FQBwAH17uE_s_GwZmv4o5rGLCKuZnFbMV31nvfWU</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2985944162</pqid></control><display><type>article</type><title>The existence of senescent cells in conjunctival epithelium from elderly individuals</title><source>Springer Nature</source><creator>Tomioka, Yasufumi ; Kitazawa, Koji ; Numa, Kohsaku ; Hughes, Jun-Wei B. ; Yokoi, Norihiko ; Sotozono, Chie</creator><creatorcontrib>Tomioka, Yasufumi ; Kitazawa, Koji ; Numa, Kohsaku ; Hughes, Jun-Wei B. ; Yokoi, Norihiko ; Sotozono, Chie</creatorcontrib><description>Purpose
The ocular surface microenvironment changes with aging. However, it remains unclear if cellular senescence influences the ocular surface. We investigated the presence of p16
INK4a
-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 (p16
INK4a
)
and
CDKN1A (p21
CIP1/WAF1
)
and immunostaining was performed to examine the expression of the senescence marker p16
INK4a
, 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
p16
INK4a
was significantly increased at the RNA level in the elderly compared to middle-aged (
p
< 0.05). Positivity rate of p16
INK4a
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
INK4a
-positivity but retained in tissue samples in which p16
INK4a
was undetectable.
Conclusions
Senescent cells accumulate with age in the conjunctival epithelium, accompanied by a decrease in Ki67, p63 and ZO-1 expressing cells.</description><identifier>ISSN: 0021-5155</identifier><identifier>EISSN: 1613-2246</identifier><identifier>DOI: 10.1007/s10384-023-01047-x</identifier><identifier>PMID: 38311689</identifier><language>eng</language><publisher>Tokyo: Springer Japan</publisher><subject>Aged ; Aged, 80 and over ; Aging ; Biomarkers ; Cellular Senescence ; Conjunctiva ; Cyclin-Dependent Kinase Inhibitor p16 - analysis ; Cyclin-Dependent Kinase Inhibitor p16 - genetics ; Cyclin-Dependent Kinase Inhibitor p16 - metabolism ; Cyclin-dependent kinase inhibitor p21 ; Epithelium ; Epithelium - chemistry ; Epithelium - metabolism ; Female ; Geriatrics ; Humans ; INK4a protein ; Ki-67 Antigen ; Laboratory Investigation ; Male ; Medicine ; Medicine & Public Health ; Men ; Microenvironments ; Middle age ; Middle Aged ; Older people ; Ophthalmology ; p16 Protein ; Senescence ; Stem cells ; Women ; Zonula occludens-1 protein</subject><ispartof>Japanese journal of ophthalmology, 2024-03, Vol.68 (2), p.157-165</ispartof><rights>Japanese Ophthalmological Society 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><rights>2024. Japanese Ophthalmological Society.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-p213t-e48c911ee22830f0c1ed4305a0f56e206ae5dca8867df564b39bb0829835b3ab3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27923,27924</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38311689$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tomioka, Yasufumi</creatorcontrib><creatorcontrib>Kitazawa, Koji</creatorcontrib><creatorcontrib>Numa, Kohsaku</creatorcontrib><creatorcontrib>Hughes, Jun-Wei B.</creatorcontrib><creatorcontrib>Yokoi, Norihiko</creatorcontrib><creatorcontrib>Sotozono, Chie</creatorcontrib><title>The existence of senescent cells in conjunctival epithelium from elderly individuals</title><title>Japanese journal of ophthalmology</title><addtitle>Jpn J Ophthalmol</addtitle><addtitle>Jpn J Ophthalmol</addtitle><description>Purpose
The ocular surface microenvironment changes with aging. However, it remains unclear if cellular senescence influences the ocular surface. We investigated the presence of p16
INK4a
-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 (p16
INK4a
)
and
CDKN1A (p21
CIP1/WAF1
)
and immunostaining was performed to examine the expression of the senescence marker p16
INK4a
, 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
p16
INK4a
was significantly increased at the RNA level in the elderly compared to middle-aged (
p
< 0.05). Positivity rate of p16
INK4a
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
INK4a
-positivity but retained in tissue samples in which p16
INK4a
was undetectable.
Conclusions
Senescent cells accumulate with age in the conjunctival epithelium, accompanied by a decrease in Ki67, p63 and ZO-1 expressing cells.</description><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Aging</subject><subject>Biomarkers</subject><subject>Cellular Senescence</subject><subject>Conjunctiva</subject><subject>Cyclin-Dependent Kinase Inhibitor p16 - analysis</subject><subject>Cyclin-Dependent Kinase Inhibitor p16 - genetics</subject><subject>Cyclin-Dependent Kinase Inhibitor p16 - metabolism</subject><subject>Cyclin-dependent kinase inhibitor p21</subject><subject>Epithelium</subject><subject>Epithelium - chemistry</subject><subject>Epithelium - metabolism</subject><subject>Female</subject><subject>Geriatrics</subject><subject>Humans</subject><subject>INK4a protein</subject><subject>Ki-67 Antigen</subject><subject>Laboratory Investigation</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Men</subject><subject>Microenvironments</subject><subject>Middle age</subject><subject>Middle Aged</subject><subject>Older people</subject><subject>Ophthalmology</subject><subject>p16 Protein</subject><subject>Senescence</subject><subject>Stem cells</subject><subject>Women</subject><subject>Zonula occludens-1 protein</subject><issn>0021-5155</issn><issn>1613-2246</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNpdkUtLw0AUhQdRbK3-ARcy4MZN9M4rmSyl-IKCm7oe8rixU5JJzCSl_fdObUVwdeDej8PhHEKuGdwzgOTBMxBaRsBFBAxkEm1PyJTFTEScy_iUTAE4ixRTakIuvF8DgOSCn5OJ0IKxWKdTslyukOLW-gFdgbStqEeHvkA30ALr2lPraNG69eiKwW6ymmJnhxXWdmxo1bcNxbrEvt4FrrQbW45Z7S_JWRUEr446Ix_PT8v5a7R4f3mbPy6ijjMxRCh1kTKGyLkWUEHBsJQCVAaVipFDnKEqi0zrOCnDReYizXPQPNVC5SLLxYzcHXy7vv0a0Q-msX6fOnPYjt7wNBShQCU6oLf_0HU79i6kC5RWqZQs5oG6OVJj3mBput42Wb8zv30FQBwAH17uE_s_GwZmv4o5rGLCKuZnFbMV31nvfWU</recordid><startdate>20240301</startdate><enddate>20240301</enddate><creator>Tomioka, Yasufumi</creator><creator>Kitazawa, Koji</creator><creator>Numa, Kohsaku</creator><creator>Hughes, Jun-Wei B.</creator><creator>Yokoi, Norihiko</creator><creator>Sotozono, Chie</creator><general>Springer Japan</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7QL</scope><scope>7T7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20240301</creationdate><title>The existence of senescent cells in conjunctival epithelium from elderly individuals</title><author>Tomioka, Yasufumi ; Kitazawa, Koji ; Numa, Kohsaku ; Hughes, Jun-Wei B. ; Yokoi, Norihiko ; Sotozono, Chie</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p213t-e48c911ee22830f0c1ed4305a0f56e206ae5dca8867df564b39bb0829835b3ab3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Aging</topic><topic>Biomarkers</topic><topic>Cellular Senescence</topic><topic>Conjunctiva</topic><topic>Cyclin-Dependent Kinase Inhibitor p16 - analysis</topic><topic>Cyclin-Dependent Kinase Inhibitor p16 - genetics</topic><topic>Cyclin-Dependent Kinase Inhibitor p16 - metabolism</topic><topic>Cyclin-dependent kinase inhibitor p21</topic><topic>Epithelium</topic><topic>Epithelium - chemistry</topic><topic>Epithelium - metabolism</topic><topic>Female</topic><topic>Geriatrics</topic><topic>Humans</topic><topic>INK4a protein</topic><topic>Ki-67 Antigen</topic><topic>Laboratory Investigation</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Men</topic><topic>Microenvironments</topic><topic>Middle age</topic><topic>Middle Aged</topic><topic>Older people</topic><topic>Ophthalmology</topic><topic>p16 Protein</topic><topic>Senescence</topic><topic>Stem cells</topic><topic>Women</topic><topic>Zonula occludens-1 protein</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tomioka, Yasufumi</creatorcontrib><creatorcontrib>Kitazawa, Koji</creatorcontrib><creatorcontrib>Numa, Kohsaku</creatorcontrib><creatorcontrib>Hughes, Jun-Wei B.</creatorcontrib><creatorcontrib>Yokoi, Norihiko</creatorcontrib><creatorcontrib>Sotozono, Chie</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Japanese journal of ophthalmology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tomioka, Yasufumi</au><au>Kitazawa, Koji</au><au>Numa, Kohsaku</au><au>Hughes, Jun-Wei B.</au><au>Yokoi, Norihiko</au><au>Sotozono, Chie</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The existence of senescent cells in conjunctival epithelium from elderly individuals</atitle><jtitle>Japanese journal of ophthalmology</jtitle><stitle>Jpn J Ophthalmol</stitle><addtitle>Jpn J Ophthalmol</addtitle><date>2024-03-01</date><risdate>2024</risdate><volume>68</volume><issue>2</issue><spage>157</spage><epage>165</epage><pages>157-165</pages><issn>0021-5155</issn><eissn>1613-2246</eissn><abstract>Purpose
The ocular surface microenvironment changes with aging. However, it remains unclear if cellular senescence influences the ocular surface. We investigated the presence of p16
INK4a
-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 (p16
INK4a
)
and
CDKN1A (p21
CIP1/WAF1
)
and immunostaining was performed to examine the expression of the senescence marker p16
INK4a
, 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
p16
INK4a
was significantly increased at the RNA level in the elderly compared to middle-aged (
p
< 0.05). Positivity rate of p16
INK4a
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
INK4a
-positivity but retained in tissue samples in which p16
INK4a
was undetectable.
Conclusions
Senescent cells accumulate with age in the conjunctival epithelium, accompanied by a decrease in Ki67, p63 and ZO-1 expressing cells.</abstract><cop>Tokyo</cop><pub>Springer Japan</pub><pmid>38311689</pmid><doi>10.1007/s10384-023-01047-x</doi><tpages>9</tpages></addata></record> |
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| subjects | Aged Aged, 80 and over Aging Biomarkers Cellular Senescence Conjunctiva Cyclin-Dependent Kinase Inhibitor p16 - analysis Cyclin-Dependent Kinase Inhibitor p16 - genetics Cyclin-Dependent Kinase Inhibitor p16 - metabolism Cyclin-dependent kinase inhibitor p21 Epithelium Epithelium - chemistry Epithelium - metabolism Female Geriatrics Humans INK4a protein Ki-67 Antigen Laboratory Investigation Male Medicine Medicine & Public Health Men Microenvironments Middle age Middle Aged Older people Ophthalmology p16 Protein Senescence Stem cells Women Zonula occludens-1 protein |
| title | The existence of senescent cells in conjunctival epithelium from elderly individuals |
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