Apurinic/apyrimidinic endonuclease 1, p53, and thioredoxin are linked in control of aging in C. elegans

• Verfasst von: Schlotterer, Andrea [VerfasserIn]
• Verfasst von: Hamann, Andreas [VerfasserIn]
• Verfasst von: Kukudov, Georgi [VerfasserIn]
• Verfasst von: Ibrahim, Youssef [VerfasserIn]
• Verfasst von: Heckmann, Britta [VerfasserIn]
• Verfasst von: Bozorgmehr, Farastuk [VerfasserIn]
• Verfasst von: Pfeiffer, Michael [VerfasserIn]
• Verfasst von: Hutter, Harald [VerfasserIn]
• Verfasst von: Stern, David [VerfasserIn]
• Verfasst von: Du, Xueliang [VerfasserIn]
• Verfasst von: Brownlee, Michael [VerfasserIn]
• Verfasst von: Bierhaus, Angelika [VerfasserIn]
• Verfasst von: Nawroth, Peter Paul [VerfasserIn]
• Verfasst von: Morcos, Michael [VerfasserIn]
• Titel: Apurinic/apyrimidinic endonuclease 1, p53, and thioredoxin are linked in control of aging in C. elegans
• Verf.angabe: Andreas Schlotterer, Andreas Hamann, Georgi Kukudov, Youssef Ibrahim, Britta Heckmann, Farastuk Bozorgmehr, Michael Pfeiffer, Harald Hutter, David Stern, Xueliang Du, Michael Brownlee, Angelika Bierhaus, Peter Nawroth and Michael Morcos
• E-Jahr: 2010
• Jahr: 18 May 2010
• Umfang: 13 S.
• Fussnoten: Gesehen am 13.06.2023
• Titel Quelle: Enthalten in: Aging cell
• Ort Quelle: Oxford [u.a.] : Wiley-Blackwell, 2002
• Jahr Quelle: 2010
• Band/Heft Quelle: 9(2010), 3 vom: Juni, Seite 420-432
• ISSN Quelle: 1474-9726
• DOI: doi:10.1111/j.1474-9726.2010.00572.x
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Aging
• Sach-SW: C. elegans
• Sach-SW: DNA repair
• Sach-SW: mitochondrial DNA
• Sach-SW: p53
• Sach-SW: reactive oxygen species
• K10plus-PPN: 1848857705

Abstract

Deletions in mitochondrial DNA (mtDNA) accumulate during aging. Expression of the Caenorhabditis elegans apurinic/apyrimidinic endonuclease 1 (APE1) ortholog exo-3, involved in DNA repair, is reduced by 45% (P < 0.05) during aging of C. elegans. Suppression of exo-3 by treatment with RNAi resulted in a threefold increase in mtDNA deletions (P < 0.05), twofold enhanced generation of reactive oxygen species (ROS) (P < 0.01), distortion of the structural integrity of the nervous system, reduction of head motility by 43% (P < 0.01) and whole animal motility by 38% (P < 0.05). Suppression of exo-3 significantly reduced life span: mean life span decreased from 18.5 ± 0.4 to 15.4 ± 0.1 days (P < 0.001) and maximum life span from 25.9 ± 0.4 to 23.2 ± 0.1 days (P = 0.001). Additional treatment of exo-3-suppressed animals with a mitochondrial uncoupler decreased ROS levels, reduced neuronal damage, and increased motility and life span. Additional suppression of the C. elegans p53 ortholog cep-1 in exo-3 RNAi-treated animals similarly decreased ROS levels, preserved neuronal integrity, and increased motility and life span. In wild-type animals, suppression of cep-1, involved in downregulation of exo-3, increased expression of exo-3 without a significant effect on ROS levels, preserved neuronal integrity, and increased motility and life span. Suppression of the C. elegans thioredoxin orthologs trx-1 and trx-2, involved in the redox chaperone activity of exo-3, overrides the protective effect of cep-1 RNAi treatment on neuronal integrity, neuronal function, mean and maximum life span. These results show that APE1/EXO-3, p53/CEP-1, and thioredoxin affect each other and that these interactions determine aging as well as neuronal structure and function.