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Heart‐Specific Overexpression of FOXO Ameliorates Performance Decline through Enhanced UPS Processing in Aging Drosophila
Author(s) -
BliceBaum A,
Viswanathan M,
Mullinax B,
Zambon A,
Kaushik G,
Engler A,
Bodmer R,
Cammarato A
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.726.10
Subject(s) - autophagy , drosophila melanogaster , ubiquitin , biology , proteasome , microbiology and biotechnology , transcriptome , transcription factor , ageing , gene expression , medicine , endocrinology , gene , genetics , apoptosis
Heart performance declines with age. Reduced protein quality control due to decreased function of the ubiquitin/proteasome system (UPS) and autophagy is a likely contributor to age‐associated cardiac dysfunction. The transcription factor FOXO has been shown to be involved in the regulation of genes involved in both as well as a host of other processes. Here, the effect of overexpression (OE) of dFOXO was investigated in Drosophila melanogaster, a rapidly aging model in which the tissue‐specific UAS‐GAL4 expression system is often exploited. This system permitted different extents of heart‐restricted dFOXO OE. Excessive dFOXO doses proved fatal while mild levels appeared cardioprotective, ameliorating functional decline as determined by high‐speed video microscopy and motion analysis of aging hearts. OE of dFOXO in all muscle was previously shown to increase lifespan, likely caused by systemic expression of autophagy related proteins and reduced ubiquitin content. Similarly, in this study dFOXO‐mediated improvement in heart function with age was also accompanied by a significant decrease in ubiquitinated myocardial proteins as determined by quantitative western blot. However, microarray data suggested that this reduction was caused by increased expression of genes associated with UPS rather than autophagy, indicating FOXO may perform its function differently in the heart than in other striated muscles. FOXO gene candidates from the transcriptomic analysis will be probed to pinpoint how mild FOXO OE halts the natural decline in heart performance in Drosophila.