Dominant-negative Dmp53 extends life span through the dTOR pathway in D. melanogaster.

Mechanisms of Ageing and Development
Johannes H BauerStephen L Helfand

Abstract

Expression of dominant-negative (DN) versions of the Drosophila ortholog of the tumor suppressor p53 extends fly life span in a Calorie Restriction (CR) dependent manner. DN-Dmp53 expression furthermore leads to reduction of Drosophila insulin-like peptide (dILP) 2 mRNA levels and a decrease in insulin/insulin-like growth factor-signaling activity (IIS) in the fly fat body. It is unclear by which mechanisms DN-Dmp53 extends longevity, and whether modulation of insulin-signaling activity plays a pivotal role in life span regulation by Dmp53. Here we show that life span extension due to DN-Dmp53 expression is likely due to reduction of Dmp53 activity and that decreased Dmp53 activity does not extend life span when dILP2 is concomitantly over expressed. Furthermore, extended longevity due to DN-Dmp53 expression does not further extend the life span of flies over expressing the IIS associated transcription factor dFoxO, indicating that DN-Dmp53-dependent life span extension may be related to IIS. However, reduction of dFoxO levels does not decrease DN-Dmp53-dependent longevity extension. Interestingly, when DN-Dmp53 is expressed in flies lacking the translation initiation controlling factor Thor/4E-BP, the downstream target of dTOR...Continue Reading

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Citations

Apr 18, 2015·Cell Death and Differentiation·B ZhangB R Calvi
May 1, 2012·Biochimica Et Biophysica Acta·Siti Nur Sarah MorrisJohannes H Bauer
Aug 24, 2010·Experimental Gerontology·Stewart FrankelBlanka Rogina
Aug 30, 2018·Journal of Research on Adolescence : the Official Journal of the Society for Research on Adolescence·Igor EsnaolaLorea Azpiazu
Jul 20, 2017·Npj Aging and Mechanisms of Disease·Inge SeimVadim N Gladyshev
Jan 24, 2016·Cold Spring Harbor Perspectives in Medicine·Sebastien M Joruiz, Jean-Christophe Bourdon

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