Continuous overexpression of thioredoxin 1 enhances cancer development and does not extend maximum lifespan in male C57BL/6 mice.
Identifieur interne : 000278 ( Main/Exploration ); précédent : 000277; suivant : 000279Continuous overexpression of thioredoxin 1 enhances cancer development and does not extend maximum lifespan in male C57BL/6 mice.
Auteurs : Lisa C. Flores [États-Unis] ; Madeline G. Roman [États-Unis] ; Geneva M. Cunningham [États-Unis] ; Christie Cheng [États-Unis] ; Sara Dube [États-Unis] ; Colton Allen [États-Unis] ; Holly Van Remmen [États-Unis] ; Gene B. Hubbard [États-Unis] ; Thomas L. Saunders [États-Unis] ; Yuji Ikeno [États-Unis]Source :
- Pathobiology of aging & age related diseases [ 2001-0001 ] ; 2018.
Abstract
We examined the effects of continuous overexpression of thioredoxin (Trx) 1 on aging in Trx1 transgenic mice [Tg(TXN)+/0]. This study was conducted to test whether increased thioredoxin expression over the lifespan in mice would alter aging and age-related pathology because our previous study demonstrated that Tg(act-TXN)+/0 mice had no significant maximum life extension, possibly due to the use of actin as a promoter, which may have resulted in loss of Trx1 overexpression during aging. To test this hypothesis, we generated new Trx1 transgenic mice using a fragment of the human genome containing the TXN gene with an endogenous promoter to ensure continuous overexpression of Trx1 throughout the lifespan. Universal overexpression of Trx1 was observed, and Trx1 overexpression was maintained during aging (up to 22-24 months old) in the Tg(TXN)+/0 mice. The levels of Trx1 are significantly higher (approximately 4 to 31 fold) in all of the tissues examined in the Tg(TXN)+/0 mice compared to the wild-type (WT) littermates. The overexpression of Trx1 did not cause any changes in the levels of Trx2, glutaredoxin, glutathione, or other major antioxidant enzymes. The survival study demonstrated that male Tg(TXN)+/0 mice slightly extended the earlier part of the lifespan compared to WT littermates, but no significant life extension was observed over the lifespan. The cross-sectional pathological analysis (22-25 months old) showed that Tg(TXN)+/0 mice had a significantly higher severity of lymphoma and more tumor burden than WT mice, which was associated with the suppression of the apoptosis signal-regulating kinase 1 (ASK1) pathway. Our findings suggest that the increased levels of Trx1 over the lifespan in Tg(TXN)+/0 mice showed some beneficial effects (slight extension of lifespan) in the earlier part of life but had no significant effects on median or maximum lifespans, and increased Trx1 levels enhanced tumor development in old mice.
DOI: 10.1080/20010001.2018.1533754
PubMed: 30370017
PubMed Central: PMC6201794
Affiliations:
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Roman</name><affiliation wicri:level="2"><nlm:affiliation>Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, TX</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Cunningham, Geneva M" sort="Cunningham, Geneva M" uniqKey="Cunningham G" first="Geneva M" last="Cunningham">Geneva M. 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Hubbard</name><affiliation wicri:level="2"><nlm:affiliation>Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, TX</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Department of Pathology, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology, The University of Texas Health Science Center at San Antonio, San Antonio, TX</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Saunders, Thomas L" sort="Saunders, Thomas L" uniqKey="Saunders T" first="Thomas L" last="Saunders">Thomas L. Saunders</name><affiliation wicri:level="2"><nlm:affiliation>Transgenic Animal Model Core, University of Michigan, Ann Arbor, MI, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Transgenic Animal Model Core, University of Michigan, Ann Arbor, MI</wicri:regionArea><placeName><region type="state">Michigan</region></placeName></affiliation></author><author><name sortKey="Ikeno, Yuji" sort="Ikeno, Yuji" uniqKey="Ikeno Y" first="Yuji" last="Ikeno">Yuji Ikeno</name><affiliation wicri:level="2"><nlm:affiliation>Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, TX</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Department of Pathology, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology, The University of Texas Health Science Center at San Antonio, San Antonio, TX</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Geriatric Research Education and Clinical Center (GRECC), Audie L. Murphy VA Hospital, South Texas Veterans Health Care System, San Antonio, TX, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Geriatric Research Education and Clinical Center (GRECC), Audie L. Murphy VA Hospital, South Texas Veterans Health Care System, San Antonio, TX</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2018">2018</date><idno type="RBID">pubmed:30370017</idno><idno type="pmid">30370017</idno><idno type="doi">10.1080/20010001.2018.1533754</idno><idno type="pmc">PMC6201794</idno><idno type="wicri:Area/Main/Corpus">000198</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000198</idno><idno type="wicri:Area/Main/Curation">000198</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Curation">000198</idno><idno type="wicri:Area/Main/Exploration">000198</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Continuous overexpression of thioredoxin 1 enhances cancer development and does not extend maximum lifespan in male C57BL/6 mice.</title><author><name sortKey="Flores, Lisa C" sort="Flores, Lisa C" uniqKey="Flores L" first="Lisa C" last="Flores">Lisa C. Flores</name><affiliation wicri:level="2"><nlm:affiliation>Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, TX</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Roman, Madeline G" sort="Roman, Madeline G" uniqKey="Roman M" first="Madeline G" last="Roman">Madeline G. Roman</name><affiliation wicri:level="2"><nlm:affiliation>Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, TX</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Cunningham, Geneva M" sort="Cunningham, Geneva M" uniqKey="Cunningham G" first="Geneva M" last="Cunningham">Geneva M. Cunningham</name><affiliation wicri:level="2"><nlm:affiliation>Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, TX</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Cheng, Christie" sort="Cheng, Christie" uniqKey="Cheng C" first="Christie" last="Cheng">Christie Cheng</name><affiliation wicri:level="2"><nlm:affiliation>Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, TX</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Dube, Sara" sort="Dube, Sara" uniqKey="Dube S" first="Sara" last="Dube">Sara Dube</name><affiliation wicri:level="2"><nlm:affiliation>Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, TX</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Allen, Colton" sort="Allen, Colton" uniqKey="Allen C" first="Colton" last="Allen">Colton Allen</name><affiliation wicri:level="2"><nlm:affiliation>Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, TX</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Van Remmen, Holly" sort="Van Remmen, Holly" uniqKey="Van Remmen H" first="Holly" last="Van Remmen">Holly Van Remmen</name><affiliation wicri:level="2"><nlm:affiliation>Aging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Aging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK</wicri:regionArea><placeName><region type="state">Oklahoma</region></placeName></affiliation></author><author><name sortKey="Hubbard, Gene B" sort="Hubbard, Gene B" uniqKey="Hubbard G" first="Gene B" last="Hubbard">Gene B. Hubbard</name><affiliation wicri:level="2"><nlm:affiliation>Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, TX</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Department of Pathology, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology, The University of Texas Health Science Center at San Antonio, San Antonio, TX</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Saunders, Thomas L" sort="Saunders, Thomas L" uniqKey="Saunders T" first="Thomas L" last="Saunders">Thomas L. Saunders</name><affiliation wicri:level="2"><nlm:affiliation>Transgenic Animal Model Core, University of Michigan, Ann Arbor, MI, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Transgenic Animal Model Core, University of Michigan, Ann Arbor, MI</wicri:regionArea><placeName><region type="state">Michigan</region></placeName></affiliation></author><author><name sortKey="Ikeno, Yuji" sort="Ikeno, Yuji" uniqKey="Ikeno Y" first="Yuji" last="Ikeno">Yuji Ikeno</name><affiliation wicri:level="2"><nlm:affiliation>Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, TX</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Department of Pathology, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology, The University of Texas Health Science Center at San Antonio, San Antonio, TX</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Geriatric Research Education and Clinical Center (GRECC), Audie L. Murphy VA Hospital, South Texas Veterans Health Care System, San Antonio, TX, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Geriatric Research Education and Clinical Center (GRECC), Audie L. Murphy VA Hospital, South Texas Veterans Health Care System, San Antonio, TX</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation></author></analytic><series><title level="j">Pathobiology of aging & age related diseases</title><idno type="ISSN">2001-0001</idno><imprint><date when="2018" type="published">2018</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">We examined the effects of continuous overexpression of thioredoxin (Trx) 1 on aging in Trx1 transgenic mice [Tg(<i>TXN</i>)<sup>+/0</sup>]. This study was conducted to test whether increased thioredoxin expression over the lifespan in mice would alter aging and age-related pathology because our previous study demonstrated that Tg(act-<i>TXN</i>)<sup>+/0</sup> mice had no significant maximum life extension, possibly due to the use of actin as a promoter, which may have resulted in loss of Trx1 overexpression during aging. To test this hypothesis, we generated new Trx1 transgenic mice using a fragment of the human genome containing the <i>TXN</i> gene with an endogenous promoter to ensure continuous overexpression of Trx1 throughout the lifespan. Universal overexpression of Trx1 was observed, and Trx1 overexpression was maintained during aging (up to 22-24 months old) in the Tg(<i>TXN</i>)<sup>+/0</sup> mice. The levels of Trx1 are significantly higher (approximately 4 to 31 fold) in all of the tissues examined in the Tg(<i>TXN</i>)<sup>+/0</sup> mice compared to the wild-type (WT) littermates. The overexpression of Trx1 did not cause any changes in the levels of Trx2, glutaredoxin, glutathione, or other major antioxidant enzymes. The survival study demonstrated that male Tg(<i>TXN</i>)<sup>+/0</sup> mice slightly extended the earlier part of the lifespan compared to WT littermates, but no significant life extension was observed over the lifespan. The cross-sectional pathological analysis (22-25 months old) showed that Tg(<i>TXN</i>)<sup>+/0</sup> mice had a significantly higher severity of lymphoma and more tumor burden than WT mice, which was associated with the suppression of the apoptosis signal-regulating kinase 1 (ASK1) pathway. Our findings suggest that the increased levels of Trx1 over the lifespan in Tg(<i>TXN</i>)<sup>+/0</sup> mice showed some beneficial effects (slight extension of lifespan) in the earlier part of life but had no significant effects on median or maximum lifespans, and increased Trx1 levels enhanced tumor development in old mice.</div></front></TEI><pubmed><MedlineCitation Status="PubMed-not-MEDLINE" Owner="NLM"><PMID Version="1">30370017</PMID><DateRevised><Year>2020</Year><Month>10</Month><Day>01</Day></DateRevised><Article PubModel="Electronic-eCollection"><Journal><ISSN IssnType="Print">2001-0001</ISSN><JournalIssue CitedMedium="Print"><Volume>8</Volume><Issue>1</Issue><PubDate><Year>2018</Year></PubDate></JournalIssue><Title>Pathobiology of aging & age related diseases</Title><ISOAbbreviation>Pathobiol Aging Age Relat Dis</ISOAbbreviation></Journal><ArticleTitle>Continuous overexpression of thioredoxin 1 enhances cancer development and does not extend maximum lifespan in male C57BL/6 mice.</ArticleTitle><Pagination><MedlinePgn>1533754</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1080/20010001.2018.1533754</ELocationID><Abstract><AbstractText>We examined the effects of continuous overexpression of thioredoxin (Trx) 1 on aging in Trx1 transgenic mice [Tg(<i>TXN</i>)<sup>+/0</sup>]. This study was conducted to test whether increased thioredoxin expression over the lifespan in mice would alter aging and age-related pathology because our previous study demonstrated that Tg(act-<i>TXN</i>)<sup>+/0</sup> mice had no significant maximum life extension, possibly due to the use of actin as a promoter, which may have resulted in loss of Trx1 overexpression during aging. To test this hypothesis, we generated new Trx1 transgenic mice using a fragment of the human genome containing the <i>TXN</i> gene with an endogenous promoter to ensure continuous overexpression of Trx1 throughout the lifespan. Universal overexpression of Trx1 was observed, and Trx1 overexpression was maintained during aging (up to 22-24 months old) in the Tg(<i>TXN</i>)<sup>+/0</sup> mice. The levels of Trx1 are significantly higher (approximately 4 to 31 fold) in all of the tissues examined in the Tg(<i>TXN</i>)<sup>+/0</sup> mice compared to the wild-type (WT) littermates. The overexpression of Trx1 did not cause any changes in the levels of Trx2, glutaredoxin, glutathione, or other major antioxidant enzymes. The survival study demonstrated that male Tg(<i>TXN</i>)<sup>+/0</sup> mice slightly extended the earlier part of the lifespan compared to WT littermates, but no significant life extension was observed over the lifespan. The cross-sectional pathological analysis (22-25 months old) showed that Tg(<i>TXN</i>)<sup>+/0</sup> mice had a significantly higher severity of lymphoma and more tumor burden than WT mice, which was associated with the suppression of the apoptosis signal-regulating kinase 1 (ASK1) pathway. Our findings suggest that the increased levels of Trx1 over the lifespan in Tg(<i>TXN</i>)<sup>+/0</sup> mice showed some beneficial effects (slight extension of lifespan) in the earlier part of life but had no significant effects on median or maximum lifespans, and increased Trx1 levels enhanced tumor development in old mice.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Flores</LastName><ForeName>Lisa C</ForeName><Initials>LC</Initials><AffiliationInfo><Affiliation>Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Roman</LastName><ForeName>Madeline G</ForeName><Initials>MG</Initials><AffiliationInfo><Affiliation>Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cunningham</LastName><ForeName>Geneva M</ForeName><Initials>GM</Initials><AffiliationInfo><Affiliation>Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cheng</LastName><ForeName>Christie</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Dube</LastName><ForeName>Sara</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Allen</LastName><ForeName>Colton</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Van Remmen</LastName><ForeName>Holly</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Aging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hubbard</LastName><ForeName>Gene B</ForeName><Initials>GB</Initials><AffiliationInfo><Affiliation>Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Pathology, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Saunders</LastName><ForeName>Thomas L</ForeName><Initials>TL</Initials><AffiliationInfo><Affiliation>Transgenic Animal Model Core, University of Michigan, Ann Arbor, MI, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ikeno</LastName><ForeName>Yuji</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Pathology, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Geriatric Research Education and Clinical Center (GRECC), Audie L. Murphy VA Hospital, South Texas Veterans Health Care System, San Antonio, TX, USA.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2018</Year><Month>10</Month><Day>23</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Pathobiol Aging Age Relat Dis</MedlineTA><NlmUniqueID>101575310</NlmUniqueID><ISSNLinking>2001-0001</ISSNLinking></MedlineJournalInfo><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Thioredoxin (Trx)</Keyword><Keyword MajorTopicYN="N">aging</Keyword><Keyword MajorTopicYN="N">cancer</Keyword><Keyword MajorTopicYN="N">oxidative stress</Keyword><Keyword MajorTopicYN="N">transgenic mouse (Tg)</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2018</Year><Month>05</Month><Day>03</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2018</Year><Month>08</Month><Day>14</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2018</Year><Month>09</Month><Day>20</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2018</Year><Month>10</Month><Day>30</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2018</Year><Month>10</Month><Day>30</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2018</Year><Month>10</Month><Day>30</Day><Hour>6</Hour><Minute>1</Minute></PubMedPubDate></History><PublicationStatus>epublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">30370017</ArticleId><ArticleId IdType="doi">10.1080/20010001.2018.1533754</ArticleId><ArticleId IdType="pii">1533754</ArticleId><ArticleId IdType="pmc">PMC6201794</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>J 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Hubbard</name><name sortKey="Ikeno, Yuji" sort="Ikeno, Yuji" uniqKey="Ikeno Y" first="Yuji" last="Ikeno">Yuji Ikeno</name><name sortKey="Ikeno, Yuji" sort="Ikeno, Yuji" uniqKey="Ikeno Y" first="Yuji" last="Ikeno">Yuji Ikeno</name><name sortKey="Ikeno, Yuji" sort="Ikeno, Yuji" uniqKey="Ikeno Y" first="Yuji" last="Ikeno">Yuji Ikeno</name><name sortKey="Roman, Madeline G" sort="Roman, Madeline G" uniqKey="Roman M" first="Madeline G" last="Roman">Madeline G. Roman</name><name sortKey="Saunders, Thomas L" sort="Saunders, Thomas L" uniqKey="Saunders T" first="Thomas L" last="Saunders">Thomas L. Saunders</name><name sortKey="Van Remmen, Holly" sort="Van Remmen, Holly" uniqKey="Van Remmen H" first="Holly" last="Van Remmen">Holly Van Remmen</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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