Senescence-related genes possibly responsible for poor liver regeneration after hepatectomy in elderly patients
Background and Aim Liver regeneration likely decreases with age by an, as yet, incompletely understood mechanism, restricting the extent of hepatectomy. We therefore analyzed the effect of aging on liver regeneration and investigated mechanisms associate with poor regeneration of human liver. Method...
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| Veröffentlicht in: | Journal of gastroenterology and hepatology 2014-05, Vol.29 (5), p.1102-1108 |
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| creator | Zhu, Chengzhan Ikemoto, Tetsuya Utsunomiya, Tohru Yamada, Shinichiro Morine, Yuji Imura, Satoru Arakawa, Yusuke Takasu, Chie Ishikawa, Daichi Shimada, Mitsuo |
| description | Background and Aim
Liver regeneration likely decreases with age by an, as yet, incompletely understood mechanism, restricting the extent of hepatectomy. We therefore analyzed the effect of aging on liver regeneration and investigated mechanisms associate with poor regeneration of human liver.
Methods
We assessed 130 patients who underwent hepatectomy at our institute between 2005 and 2012. The patients were divided into two groups, a younger (age 65 years, n = 71) group. The expression of hepatocyte growth factor (HGF), its ligand Met, and the senescence‐related genes p16, SIRT1 and SMP30 were assessed by qRT‐PCR. Simulated preoperative and 1 week and 6 month postoperative liver volumes were evaluated in 11 younger and 11 older patients using a 3D simulation imaging system. Regenerated liver volumes were calculated and compared with clinicopathological factors, and correlations between liver regeneration and gene expression were calculated.
Results
HGF and Met expression was significantly lower, and p16 expression significantly higher in older than in younger patients (P |
| doi_str_mv | 10.1111/jgh.12468 |
| format | Article |
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Liver regeneration likely decreases with age by an, as yet, incompletely understood mechanism, restricting the extent of hepatectomy. We therefore analyzed the effect of aging on liver regeneration and investigated mechanisms associate with poor regeneration of human liver.
Methods
We assessed 130 patients who underwent hepatectomy at our institute between 2005 and 2012. The patients were divided into two groups, a younger (age < 65 years, n = 59) and an older (age > 65 years, n = 71) group. The expression of hepatocyte growth factor (HGF), its ligand Met, and the senescence‐related genes p16, SIRT1 and SMP30 were assessed by qRT‐PCR. Simulated preoperative and 1 week and 6 month postoperative liver volumes were evaluated in 11 younger and 11 older patients using a 3D simulation imaging system. Regenerated liver volumes were calculated and compared with clinicopathological factors, and correlations between liver regeneration and gene expression were calculated.
Results
HGF and Met expression was significantly lower, and p16 expression significantly higher in older than in younger patients (P < 0.05 each). Mean increases in liver volume after 6 months were significantly greater in younger than in older patients (396.5 mL, 45.6% vs 159.4 mL, 23.3%, P < 0.05) but did not differ significantly at 1 week. Furthermore, p16 expression was negatively correlated with liver regeneration in older patients (R = −0.67, P < 0.05).
Conclusion
Poor liver regeneration in older patients may be associated with the upregulation of senescence‐related genes, such as p16, and the downregulation of regeneration‐promoting genes, such as HGF and Met.</description><identifier>ISSN: 0815-9319</identifier><identifier>EISSN: 1440-1746</identifier><identifier>DOI: 10.1111/jgh.12468</identifier><identifier>PMID: 24325248</identifier><language>eng</language><publisher>Australia: Blackwell Publishing Ltd</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Aging - genetics ; Calcium-Binding Proteins - genetics ; Calcium-Binding Proteins - metabolism ; Cyclin-Dependent Kinase Inhibitor p16 ; Down-Regulation - genetics ; Female ; Gene Expression - genetics ; Hepatectomy ; Hepatocyte Growth Factor - genetics ; Hepatocyte Growth Factor - metabolism ; HGF ; Humans ; Intracellular Signaling Peptides and Proteins - genetics ; Intracellular Signaling Peptides and Proteins - metabolism ; liver regeneration ; Liver Regeneration - genetics ; Male ; Met ; Middle Aged ; Neoplasm Proteins - genetics ; Neoplasm Proteins - metabolism ; p16 ; Proto-Oncogene Proteins c-met - genetics ; Proto-Oncogene Proteins c-met - metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; senescence ; Sirtuin 1 - genetics ; Sirtuin 1 - metabolism ; Up-Regulation - genetics</subject><ispartof>Journal of gastroenterology and hepatology, 2014-05, Vol.29 (5), p.1102-1108</ispartof><rights>2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd</rights><rights>2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4628-90cdb1c2a982b98434e5b30e6e6ad9778b353baef53860d6bde81e8ee033227b3</citedby><cites>FETCH-LOGICAL-c4628-90cdb1c2a982b98434e5b30e6e6ad9778b353baef53860d6bde81e8ee033227b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fjgh.12468$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fjgh.12468$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24325248$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhu, Chengzhan</creatorcontrib><creatorcontrib>Ikemoto, Tetsuya</creatorcontrib><creatorcontrib>Utsunomiya, Tohru</creatorcontrib><creatorcontrib>Yamada, Shinichiro</creatorcontrib><creatorcontrib>Morine, Yuji</creatorcontrib><creatorcontrib>Imura, Satoru</creatorcontrib><creatorcontrib>Arakawa, Yusuke</creatorcontrib><creatorcontrib>Takasu, Chie</creatorcontrib><creatorcontrib>Ishikawa, Daichi</creatorcontrib><creatorcontrib>Shimada, Mitsuo</creatorcontrib><title>Senescence-related genes possibly responsible for poor liver regeneration after hepatectomy in elderly patients</title><title>Journal of gastroenterology and hepatology</title><addtitle>J Gastroenterol Hepatol</addtitle><description>Background and Aim
Liver regeneration likely decreases with age by an, as yet, incompletely understood mechanism, restricting the extent of hepatectomy. We therefore analyzed the effect of aging on liver regeneration and investigated mechanisms associate with poor regeneration of human liver.
Methods
We assessed 130 patients who underwent hepatectomy at our institute between 2005 and 2012. The patients were divided into two groups, a younger (age < 65 years, n = 59) and an older (age > 65 years, n = 71) group. The expression of hepatocyte growth factor (HGF), its ligand Met, and the senescence‐related genes p16, SIRT1 and SMP30 were assessed by qRT‐PCR. Simulated preoperative and 1 week and 6 month postoperative liver volumes were evaluated in 11 younger and 11 older patients using a 3D simulation imaging system. Regenerated liver volumes were calculated and compared with clinicopathological factors, and correlations between liver regeneration and gene expression were calculated.
Results
HGF and Met expression was significantly lower, and p16 expression significantly higher in older than in younger patients (P < 0.05 each). Mean increases in liver volume after 6 months were significantly greater in younger than in older patients (396.5 mL, 45.6% vs 159.4 mL, 23.3%, P < 0.05) but did not differ significantly at 1 week. Furthermore, p16 expression was negatively correlated with liver regeneration in older patients (R = −0.67, P < 0.05).
Conclusion
Poor liver regeneration in older patients may be associated with the upregulation of senescence‐related genes, such as p16, and the downregulation of regeneration‐promoting genes, such as HGF and Met.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Aging - genetics</subject><subject>Calcium-Binding Proteins - genetics</subject><subject>Calcium-Binding Proteins - metabolism</subject><subject>Cyclin-Dependent Kinase Inhibitor p16</subject><subject>Down-Regulation - genetics</subject><subject>Female</subject><subject>Gene Expression - genetics</subject><subject>Hepatectomy</subject><subject>Hepatocyte Growth Factor - genetics</subject><subject>Hepatocyte Growth Factor - metabolism</subject><subject>HGF</subject><subject>Humans</subject><subject>Intracellular Signaling Peptides and Proteins - genetics</subject><subject>Intracellular Signaling Peptides and Proteins - metabolism</subject><subject>liver regeneration</subject><subject>Liver Regeneration - genetics</subject><subject>Male</subject><subject>Met</subject><subject>Middle Aged</subject><subject>Neoplasm Proteins - genetics</subject><subject>Neoplasm Proteins - metabolism</subject><subject>p16</subject><subject>Proto-Oncogene Proteins c-met - genetics</subject><subject>Proto-Oncogene Proteins c-met - metabolism</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>senescence</subject><subject>Sirtuin 1 - genetics</subject><subject>Sirtuin 1 - metabolism</subject><subject>Up-Regulation - genetics</subject><issn>0815-9319</issn><issn>1440-1746</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUlPwzAQhS0EgrIc-AMoRzikeI9zRCwtqIDEIo6WnUzAkCbBToH-e1wK3BA-2KM33zzJ8xDaJXhI4jl8fnwaEsqlWkEDwjlOScblKhpgRUSaM5JvoM0QnjHGHGdiHW1QzqigXA1QewsNhAKaAlIPtemhTB4XUtK1IThbzxMPoWubRQ1J1frYiFft3sDH1oL1pndtk5iqj9ITdNGk6NvpPHFNAnUJPppE0UHTh220Vpk6wM73u4Xuz07vjsfp5Hp0fnw0SQsuqUpzXJSWFNTkitpcccZBWIZBgjRlnmXKMsGsgUowJXEpbQmKgALAjFGaWbaF9pe-nW9fZxB6PXXxm3VtGmhnQROpMqmEouR_VBAlKRWcRvRgiRY-bsdDpTvvpsbPNcF6EYWOUeivKCK79207s1Mof8mf3UfgcAm8uxrmfzvpi9H4xzJdTrjQw8fvhPEvWmYsE_rhaqT55fgkZw8TfcM-ARUbo7w</recordid><startdate>201405</startdate><enddate>201405</enddate><creator>Zhu, Chengzhan</creator><creator>Ikemoto, Tetsuya</creator><creator>Utsunomiya, Tohru</creator><creator>Yamada, Shinichiro</creator><creator>Morine, Yuji</creator><creator>Imura, Satoru</creator><creator>Arakawa, Yusuke</creator><creator>Takasu, Chie</creator><creator>Ishikawa, Daichi</creator><creator>Shimada, Mitsuo</creator><general>Blackwell Publishing Ltd</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>201405</creationdate><title>Senescence-related genes possibly responsible for poor liver regeneration after hepatectomy in elderly patients</title><author>Zhu, Chengzhan ; Ikemoto, Tetsuya ; Utsunomiya, Tohru ; Yamada, Shinichiro ; Morine, Yuji ; Imura, Satoru ; Arakawa, Yusuke ; Takasu, Chie ; Ishikawa, Daichi ; Shimada, Mitsuo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4628-90cdb1c2a982b98434e5b30e6e6ad9778b353baef53860d6bde81e8ee033227b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Aging - genetics</topic><topic>Calcium-Binding Proteins - genetics</topic><topic>Calcium-Binding Proteins - metabolism</topic><topic>Cyclin-Dependent Kinase Inhibitor p16</topic><topic>Down-Regulation - genetics</topic><topic>Female</topic><topic>Gene Expression - genetics</topic><topic>Hepatectomy</topic><topic>Hepatocyte Growth Factor - genetics</topic><topic>Hepatocyte Growth Factor - metabolism</topic><topic>HGF</topic><topic>Humans</topic><topic>Intracellular Signaling Peptides and Proteins - genetics</topic><topic>Intracellular Signaling Peptides and Proteins - metabolism</topic><topic>liver regeneration</topic><topic>Liver Regeneration - genetics</topic><topic>Male</topic><topic>Met</topic><topic>Middle Aged</topic><topic>Neoplasm Proteins - genetics</topic><topic>Neoplasm Proteins - metabolism</topic><topic>p16</topic><topic>Proto-Oncogene Proteins c-met - genetics</topic><topic>Proto-Oncogene Proteins c-met - metabolism</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>senescence</topic><topic>Sirtuin 1 - genetics</topic><topic>Sirtuin 1 - metabolism</topic><topic>Up-Regulation - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhu, Chengzhan</creatorcontrib><creatorcontrib>Ikemoto, Tetsuya</creatorcontrib><creatorcontrib>Utsunomiya, Tohru</creatorcontrib><creatorcontrib>Yamada, Shinichiro</creatorcontrib><creatorcontrib>Morine, Yuji</creatorcontrib><creatorcontrib>Imura, Satoru</creatorcontrib><creatorcontrib>Arakawa, Yusuke</creatorcontrib><creatorcontrib>Takasu, Chie</creatorcontrib><creatorcontrib>Ishikawa, Daichi</creatorcontrib><creatorcontrib>Shimada, Mitsuo</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>Journal of gastroenterology and hepatology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhu, Chengzhan</au><au>Ikemoto, Tetsuya</au><au>Utsunomiya, Tohru</au><au>Yamada, Shinichiro</au><au>Morine, Yuji</au><au>Imura, Satoru</au><au>Arakawa, Yusuke</au><au>Takasu, Chie</au><au>Ishikawa, Daichi</au><au>Shimada, Mitsuo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Senescence-related genes possibly responsible for poor liver regeneration after hepatectomy in elderly patients</atitle><jtitle>Journal of gastroenterology and hepatology</jtitle><addtitle>J Gastroenterol Hepatol</addtitle><date>2014-05</date><risdate>2014</risdate><volume>29</volume><issue>5</issue><spage>1102</spage><epage>1108</epage><pages>1102-1108</pages><issn>0815-9319</issn><eissn>1440-1746</eissn><abstract>Background and Aim
Liver regeneration likely decreases with age by an, as yet, incompletely understood mechanism, restricting the extent of hepatectomy. We therefore analyzed the effect of aging on liver regeneration and investigated mechanisms associate with poor regeneration of human liver.
Methods
We assessed 130 patients who underwent hepatectomy at our institute between 2005 and 2012. The patients were divided into two groups, a younger (age < 65 years, n = 59) and an older (age > 65 years, n = 71) group. The expression of hepatocyte growth factor (HGF), its ligand Met, and the senescence‐related genes p16, SIRT1 and SMP30 were assessed by qRT‐PCR. Simulated preoperative and 1 week and 6 month postoperative liver volumes were evaluated in 11 younger and 11 older patients using a 3D simulation imaging system. Regenerated liver volumes were calculated and compared with clinicopathological factors, and correlations between liver regeneration and gene expression were calculated.
Results
HGF and Met expression was significantly lower, and p16 expression significantly higher in older than in younger patients (P < 0.05 each). Mean increases in liver volume after 6 months were significantly greater in younger than in older patients (396.5 mL, 45.6% vs 159.4 mL, 23.3%, P < 0.05) but did not differ significantly at 1 week. Furthermore, p16 expression was negatively correlated with liver regeneration in older patients (R = −0.67, P < 0.05).
Conclusion
Poor liver regeneration in older patients may be associated with the upregulation of senescence‐related genes, such as p16, and the downregulation of regeneration‐promoting genes, such as HGF and Met.</abstract><cop>Australia</cop><pub>Blackwell Publishing Ltd</pub><pmid>24325248</pmid><doi>10.1111/jgh.12468</doi><tpages>7</tpages></addata></record> |
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| subjects | Adult Aged Aged, 80 and over Aging - genetics Calcium-Binding Proteins - genetics Calcium-Binding Proteins - metabolism Cyclin-Dependent Kinase Inhibitor p16 Down-Regulation - genetics Female Gene Expression - genetics Hepatectomy Hepatocyte Growth Factor - genetics Hepatocyte Growth Factor - metabolism HGF Humans Intracellular Signaling Peptides and Proteins - genetics Intracellular Signaling Peptides and Proteins - metabolism liver regeneration Liver Regeneration - genetics Male Met Middle Aged Neoplasm Proteins - genetics Neoplasm Proteins - metabolism p16 Proto-Oncogene Proteins c-met - genetics Proto-Oncogene Proteins c-met - metabolism Reverse Transcriptase Polymerase Chain Reaction senescence Sirtuin 1 - genetics Sirtuin 1 - metabolism Up-Regulation - genetics |
| title | Senescence-related genes possibly responsible for poor liver regeneration after hepatectomy in elderly patients |
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