Longevity is determined by ETS transcription factors in multiple tissues and diverse species

• DOI: 10.1371/journal.pgen.1008212
• Publication Date: 2019-07-29T13:30:07Z
• Authors: Adam J. Dobson; Richard Boulton-M...; Lara Houchou; Tatiana Svermova; Ziyu Ren; Jeremie Subrini; Mireya Vazquez-Prada; Mimoza Hoti; Maria Rodriguez-L...; Rita Ibrahim; Afroditi Gregoriou; Alexis Gkantiragas; Jürg Bähler; Marina Ezcurra; Nazif Alic
• Keywords: Forkhead Transcription Factors

Ageing populations pose one of the main public health crises our time. Reprogramming gene expression by altering activities sequence-specific transcription factors (TFs) can ameliorate deleterious effects age. Here we explore how a circuit TFs coordinates pro-longevity transcriptional outcomes, which reveals multi-tissue and multi-species role for an entire protein family: E-twenty-six (ETS) TFs. In Drosophila, reduced insulin/IGF signalling (IIS) extends lifespan coordinating activation Aop, ETS repressor, Foxo, Forkhead activator. Aop Foxo bind same genomic loci, show that, individually, they effect similar programmes in vivo. combination, both moderate or synergise with dependent on promoter context. Moreover, oppose gene-regulatory activity Pnt, Directly knocking down Pnt recapitulates aspects Aop/Foxo programme is sufficient to extend lifespan. The lifespan-limiting appears be balanced requirement metabolic regulation young flies, Aop-Pnt-Foxo determines genes, regulates lipolysis responses nutrient stress. Molecular functions are often conserved amongst TFs, prompting us examine whether other Drosophila ETS-coding genes may also affect ageing. We that five out eight play fly ageing, acting from range organs cells including intestine, adipose neurons. expand repertoire C. elegans, confirming their function ageing revealing roles physiology throughout family, within between species.