Interplay of dFOXO and Two ETS-Family Transcription Factors Determines Lifespan in

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Despite the apparent complexity of ageing, animal lifespan can be extended. Activity of Forkhead Box O (FoxO) transcription factors can prolong survival of organisms ranging from the budding yeast to the fruit fly, and FoxO gene variants are linked to human longevity. FoxOs extend lifespan by driving complex, widespread changes in gene expression. Their primary targets include a second tier of transcriptional regulators, but it remains unclear how these secondary regulators are involved in the anti-ageing programmes orchestrated by FoxOs in vivo. To elucidate the role of this second tier, we identify a transcription factor called Anterior open (Aop) as directly regulated by the single Drosophila melanogaster FoxO protein (dFOXO) in the adult fly gut. Under certain circumstances, such as co-activation of the Pointed (PNT) transcription factor, dFOXO can be detrimental to lifespan. The role of Aop is to protect from this negative synergistic effect. Additionally, activation of AOP in the fly adipose tissue can robustly extend lifespan. Our study reveals a complex interplay between two evolutionarily conserved transcriptional regulators and dFOXO in lifespan. This significance of this interplay may extend to other physiological processes where these transcription factors play important roles.

Vyšlo v časopise: Interplay of dFOXO and Two ETS-Family Transcription Factors Determines Lifespan in. PLoS Genet 10(9): e32767. doi:10.1371/journal.pgen.1004619
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004619

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