Modest overexpression of FOXO maintains cardiac proteostasis and ameliorates age-associated functional decline.

ABSTRACT: Heart performance declines with age. Impaired protein quality control (PQC), due to reduced ubiquitin-proteasome system (UPS) activity, autophagic function, and/or chaperone-mediated protein refolding, contributes to cardiac deterioration. The transcription factor FOXO participates in regulating genes involved in PQC, senescence, and numerous other processes. Here, a comprehensive approach, involving molecular genetics, novel assays to probe insect cardiac physiology, and bioinformatics, was utilized to investigate the influence of heart-restricted manipulation of dFOXO expression in the rapidly aging Drosophila melanogaster model. Modest dFOXO overexpression was cardioprotective, ameliorating nonpathological functional decline with age. This was accompanied by increased expression of gene

SUBMITTER: Blice-Baum AC 

PROVIDER: S-EPMC5242305 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature