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A multidimensional systems biology analysis of cellular senescence in aging and disease.
Avelar, Roberto A; Ortega, Javier Gómez; Tacutu, Robi; Tyler, Eleanor J; Bennett, Dominic; Binetti, Paolo; Budovsky, Arie; Chatsirisupachai, Kasit; Johnson, Emily; Murray, Alex; Shields, Samuel; Tejada-Martinez, Daniela; Thornton, Daniel; Fraifeld, Vadim E; Bishop, Cleo L; de Magalhães, João Pedro.
Afiliação
  • Avelar RA; Integrative Genomics of Ageing Group, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, L7 8TX, UK.
  • Ortega JG; Integrative Genomics of Ageing Group, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, L7 8TX, UK.
  • Tacutu R; School of Biological Sciences, Monash University, Melbourne, VIC, 3800, Australia.
  • Tyler EJ; Integrative Genomics of Ageing Group, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, L7 8TX, UK.
  • Bennett D; Computational Biology of Aging Group, Institute of Biochemistry, Romanian Academy, 060031, Bucharest, Romania.
  • Binetti P; Chronos Biosystems SRL, 060117, Bucharest, Romania.
  • Budovsky A; Centre for Cell Biology and Cutaneous Research, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, E1 2AT, UK.
  • Chatsirisupachai K; Integrative Genomics of Ageing Group, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, L7 8TX, UK.
  • Johnson E; Integrative Genomics of Ageing Group, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, L7 8TX, UK.
  • Murray A; Research and Development Authority, Barzilai Medical Center, Ashkelon, Israel.
  • Shields S; Integrative Genomics of Ageing Group, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, L7 8TX, UK.
  • Tejada-Martinez D; Integrative Genomics of Ageing Group, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, L7 8TX, UK.
  • Thornton D; Integrative Genomics of Ageing Group, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, L7 8TX, UK.
  • Fraifeld VE; Integrative Genomics of Ageing Group, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, L7 8TX, UK.
  • Bishop CL; Integrative Genomics of Ageing Group, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, L7 8TX, UK.
  • de Magalhães JP; Doctorado en Ciencias mención Ecología y Evolución, Instituto de Ciencias Ambientales y Evolutivas, Facultad de Ciencias, Universidad Austral de Chile, Independencia 631, Valdivia, Chile.
Genome Biol ; 21(1): 91, 2020 04 07.
Article em En | MEDLINE | ID: mdl-32264951
BACKGROUND: Cellular senescence, a permanent state of replicative arrest in otherwise proliferating cells, is a hallmark of aging and has been linked to aging-related diseases. Many genes play a role in cellular senescence, yet a comprehensive understanding of its pathways is still lacking. RESULTS: We develop CellAge (http://genomics.senescence.info/cells), a manually curated database of 279 human genes driving cellular senescence, and perform various integrative analyses. Genes inducing cellular senescence tend to be overexpressed with age in human tissues and are significantly overrepresented in anti-longevity and tumor-suppressor genes, while genes inhibiting cellular senescence overlap with pro-longevity and oncogenes. Furthermore, cellular senescence genes are strongly conserved in mammals but not in invertebrates. We also build cellular senescence protein-protein interaction and co-expression networks. Clusters in the networks are enriched for cell cycle and immunological processes. Network topological parameters also reveal novel potential cellular senescence regulators. Using siRNAs, we observe that all 26 candidates tested induce at least one marker of senescence with 13 genes (C9orf40, CDC25A, CDCA4, CKAP2, GTF3C4, HAUS4, IMMT, MCM7, MTHFD2, MYBL2, NEK2, NIPA2, and TCEB3) decreasing cell number, activating p16/p21, and undergoing morphological changes that resemble cellular senescence. CONCLUSIONS: Overall, our work provides a benchmark resource for researchers to study cellular senescence, and our systems biology analyses reveal new insights and gene regulators of cellular senescence.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Envelhecimento / Senescência Celular / Bases de Dados Genéticas Limite: Animals / Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Envelhecimento / Senescência Celular / Bases de Dados Genéticas Limite: Animals / Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article