Systems biology and network pharmacology of frailty reveal novel epigenetic targets and mechanisms
Identifieur interne : 000406 ( Main/Exploration ); précédent : 000405; suivant : 000407Systems biology and network pharmacology of frailty reveal novel epigenetic targets and mechanisms
Auteurs : J. C. Gomez-Verjan [Mexique] ; R. Ramírez-Aldana [Mexique] ; M. U. Pérez-Zepeda [Mexique] ; R. Quiroz-Baez [Mexique] ; A. Luna-L Pez [Mexique] ; L. M. Gutierrez Robledo [Mexique]Source :
- Scientific Reports [ 2045-2322 ] ; 2019.
Abstract
Frailty is an age-associated condition, characterized by an inappropriate response to stress that results in a higher frequency of adverse outcomes (e.g., mortality, institutionalization and disability). Some light has been shed over its genetic background, but this is still a matter of debate. In the present study, we used network biology to analyze the interactome of frailty-related genes at different levels to relate them with pathways, clinical deficits and drugs with potential therapeutic implications. Significant pathways involved in frailty: apoptosis, proteolysis, muscle proliferation, and inflammation; genes as
Url:
DOI: 10.1038/s41598-019-47087-7
PubMed: 31332237
PubMed Central: 6646318
Affiliations:
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C." last="Gomez-Verjan">J. C. Gomez-Verjan</name><affiliation wicri:level="1"><nlm:aff id="Aff1">Instituto Nacional de Geriatría (INGER), Mexico City, Mexico</nlm:aff><country xml:lang="fr">Mexique</country><wicri:regionArea>Instituto Nacional de Geriatría (INGER), Mexico City</wicri:regionArea><wicri:noRegion>Mexico City</wicri:noRegion></affiliation></author><author><name sortKey="Ramirez Aldana, R" sort="Ramirez Aldana, R" uniqKey="Ramirez Aldana R" first="R." last="Ramírez-Aldana">R. Ramírez-Aldana</name><affiliation wicri:level="1"><nlm:aff id="Aff1">Instituto Nacional de Geriatría (INGER), Mexico City, Mexico</nlm:aff><country xml:lang="fr">Mexique</country><wicri:regionArea>Instituto Nacional de Geriatría (INGER), Mexico City</wicri:regionArea><wicri:noRegion>Mexico City</wicri:noRegion></affiliation></author><author><name sortKey="Perez Zepeda, M U" sort="Perez Zepeda, M U" uniqKey="Perez Zepeda M" first="M. U." last="Pérez-Zepeda">M. U. Pérez-Zepeda</name><affiliation wicri:level="1"><nlm:aff id="Aff1">Instituto Nacional de Geriatría (INGER), Mexico City, Mexico</nlm:aff><country xml:lang="fr">Mexique</country><wicri:regionArea>Instituto Nacional de Geriatría (INGER), Mexico City</wicri:regionArea><wicri:noRegion>Mexico City</wicri:noRegion></affiliation><affiliation><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 4689 2163</institution-id><institution-id institution-id-type="GRID">grid.458365.9</institution-id><institution>Geriatric Medicine Research,</institution><institution>Dalhousie University and Nova Scotia Health Authority,</institution></institution-wrap>Halifax, NS Canada</nlm:aff><wicri:noCountry code="subfield">NS Canada</wicri:noCountry></affiliation></author><author><name sortKey="Quiroz Baez, R" sort="Quiroz Baez, R" uniqKey="Quiroz Baez R" first="R." last="Quiroz-Baez">R. Quiroz-Baez</name><affiliation wicri:level="1"><nlm:aff id="Aff1">Instituto Nacional de Geriatría (INGER), Mexico City, Mexico</nlm:aff><country xml:lang="fr">Mexique</country><wicri:regionArea>Instituto Nacional de Geriatría (INGER), Mexico City</wicri:regionArea><wicri:noRegion>Mexico City</wicri:noRegion></affiliation></author><author><name sortKey="Luna L Pez, A" sort="Luna L Pez, A" uniqKey="Luna L Pez A" first="A." last="Luna-L Pez">A. Luna-L Pez</name><affiliation wicri:level="1"><nlm:aff id="Aff1">Instituto Nacional de Geriatría (INGER), Mexico City, Mexico</nlm:aff><country xml:lang="fr">Mexique</country><wicri:regionArea>Instituto Nacional de Geriatría (INGER), Mexico City</wicri:regionArea><wicri:noRegion>Mexico City</wicri:noRegion></affiliation></author><author><name sortKey="Gutierrez Robledo, L M" sort="Gutierrez Robledo, L M" uniqKey="Gutierrez Robledo L" first="L. M." last="Gutierrez Robledo">L. M. Gutierrez Robledo</name><affiliation wicri:level="1"><nlm:aff id="Aff1">Instituto Nacional de Geriatría (INGER), Mexico City, Mexico</nlm:aff><country xml:lang="fr">Mexique</country><wicri:regionArea>Instituto Nacional de Geriatría (INGER), Mexico City</wicri:regionArea><wicri:noRegion>Mexico City</wicri:noRegion></affiliation></author></analytic><series><title level="j">Scientific Reports</title><idno type="eISSN">2045-2322</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="Par1">Frailty is an age-associated condition, characterized by an inappropriate response to stress that results in a higher frequency of adverse outcomes (e.g., mortality, institutionalization and disability). Some light has been shed over its genetic background, but this is still a matter of debate. In the present study, we used network biology to analyze the interactome of frailty-related genes at different levels to relate them with pathways, clinical deficits and drugs with potential therapeutic implications. Significant pathways involved in frailty: apoptosis, proteolysis, muscle proliferation, and inflammation; genes as <italic>FN1, APP, CREBBP, EGFR</italic> playing a role as hubs and bottlenecks in the interactome network and epigenetic factors as <italic>HIST1H3</italic> cluster and <italic>miR200</italic> family were also involved. When connecting clinical deficits and genes, we identified five clusters that give insights into the biology of frailty: cancer, glucocorticoid receptor, TNF-α, myostatin, angiotensin converter enzyme, ApoE, interleukine-12 and −18. Finally, when performing network pharmacology analysis of the target nodes, some compounds were identified as potentially therapeutic (e.g., epigallocatechin gallate and antirheumatic agents); while some other substances appeared to be toxicants that may be involved in the development of this condition.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Chen, X" uniqKey="Chen X">X Chen</name></author><author><name sortKey="Mao, G" uniqKey="Mao G">G Mao</name></author><author><name sortKey="Leng, Sx" uniqKey="Leng S">SX Leng</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cesari, M" uniqKey="Cesari M">M Cesari</name></author><author><name sortKey="Perez Zepeda, Mu" uniqKey="Perez Zepeda M">MU Pérez-Zepeda</name></author><author><name sortKey="Marzetti, E" uniqKey="Marzetti E">E Marzetti</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Partridge, L" uniqKey="Partridge L">L Partridge</name></author><author><name sortKey="Deelen, J" uniqKey="Deelen J">J Deelen</name></author><author><name sortKey="Slagboom, Pe" uniqKey="Slagboom P">PE Slagboom</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dato, S" uniqKey="Dato S">S Dato</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Afendi, Fm" uniqKey="Afendi F">FM Afendi</name></author><author><name sortKey="Kiboi, Sk" uniqKey="Kiboi S">SK Kiboi</name></author><author><name sortKey="Kanaya, S" uniqKey="Kanaya S">S Kanaya</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Barabasi, A L" uniqKey="Barabasi A">A-L Barabási</name></author><author><name sortKey="Oltvai, Zn" uniqKey="Oltvai Z">ZN Oltvai</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Valenzuela, Jf" uniqKey="Valenzuela J">JF Valenzuela</name></author><author><name sortKey="Monterola, C" uniqKey="Monterola C">C Monterola</name></author><author><name sortKey="Tong, Vjc" uniqKey="Tong V">VJC Tong</name></author><author><name sortKey="Ng, Tp" uniqKey="Ng T">TP Ng</name></author><author><name sortKey="Larbi, A" uniqKey="Larbi A">A Larbi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hopkins, Al" uniqKey="Hopkins A">AL Hopkins</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fotis, C" uniqKey="Fotis C">C Fotis</name></author><author><name sortKey="Antoranz, A" uniqKey="Antoranz A">A Antoranz</name></author><author><name sortKey="Hatziavramidis, D" uniqKey="Hatziavramidis D">D Hatziavramidis</name></author><author><name sortKey="Sakellaropoulos, T" uniqKey="Sakellaropoulos T">T Sakellaropoulos</name></author><author><name sortKey="Alexopoulos, Lg" uniqKey="Alexopoulos L">LG Alexopoulos</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Waring, Mj" uniqKey="Waring M">MJ Waring</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhao, R" uniqKey="Zhao R">R Zhao</name></author><author><name sortKey="He, Y" uniqKey="He Y">Y He</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="G Mez Verjan, Jc" uniqKey="G Mez Verjan J">JC Gómez-Verjan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hart, T" uniqKey="Hart T">T Hart</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vi A, J" uniqKey="Vi A J">J Viña</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hangelbroek, Roland W J" uniqKey="Hangelbroek R">Roland W. 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Farrell</name></author><author><name sortKey="Rockwood, K" uniqKey="Rockwood K">K Rockwood</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mitnitski, Ab" uniqKey="Mitnitski A">AB Mitnitski</name></author><author><name sortKey="Graham, Je" uniqKey="Graham J">JE Graham</name></author><author><name sortKey="Mogilner, Aj" uniqKey="Mogilner A">AJ Mogilner</name></author><author><name sortKey="Rockwood, K" uniqKey="Rockwood K">K Rockwood</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Searle, Sd" uniqKey="Searle S">SD Searle</name></author><author><name sortKey="Mitnitski, A" uniqKey="Mitnitski A">A Mitnitski</name></author><author><name sortKey="Gahbauer, Ea" uniqKey="Gahbauer E">EA Gahbauer</name></author><author><name sortKey="Gill, Tm" uniqKey="Gill T">TM Gill</name></author><author><name sortKey="Rockwood, K" uniqKey="Rockwood K">K Rockwood</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Mexique</li></country></list><tree><country name="Mexique"><noRegion><name sortKey="Gomez Verjan, J C" sort="Gomez Verjan, J C" uniqKey="Gomez Verjan J" first="J. C." last="Gomez-Verjan">J. C. Gomez-Verjan</name></noRegion><name sortKey="Gutierrez Robledo, L M" sort="Gutierrez Robledo, L M" uniqKey="Gutierrez Robledo L" first="L. M." last="Gutierrez Robledo">L. M. Gutierrez Robledo</name><name sortKey="Luna L Pez, A" sort="Luna L Pez, A" uniqKey="Luna L Pez A" first="A." last="Luna-L Pez">A. Luna-L Pez</name><name sortKey="Perez Zepeda, M U" sort="Perez Zepeda, M U" uniqKey="Perez Zepeda M" first="M. U." last="Pérez-Zepeda">M. U. Pérez-Zepeda</name><name sortKey="Quiroz Baez, R" sort="Quiroz Baez, R" uniqKey="Quiroz Baez R" first="R." last="Quiroz-Baez">R. Quiroz-Baez</name><name sortKey="Ramirez Aldana, R" sort="Ramirez Aldana, R" uniqKey="Ramirez Aldana R" first="R." last="Ramírez-Aldana">R. Ramírez-Aldana</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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