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dFOXO overexpression ameliorates age‐related degeneration of heart performance in Drosophila
Author(s) -
Mullinax Billy,
BliceBaum Anna,
Cammarato Anthony
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.946.6
Subject(s) - autophagy , proteostasis , biology , ubiquitin , proteasome , rna interference , drosophila melanogaster , foxo3 , medicine , microbiology and biotechnology , endocrinology , signal transduction , biochemistry , rna , apoptosis , gene , protein kinase b
Despite increased life expectancy, a decrease in healthy heart function with age persists. Age‐related heart degeneration can manifest itself as decreased heart rate and fractional shortening and increased arrhythmias and diastolic intervals. Such changes are conserved from humans to flies and are possibly related to a decreased ability of protein quality control systems to maintain normal protein homeostasis over time through autophagy and/or the ubiquitin‐proteosome system. Elevated expression of muscle‐specific FOXO transcription factors has been previously shown to positively affect autophagy in Drosophila and ameliorate the accumulation of ubiquitinated proteins systemically with age. We hypothesize that mild overexpression of heart‐specific dFOXO will have a cardioprotective effect in aging Drosophila. By aging FOXO and control flies to seven weeks, we compared indices of cardiac function at various time points using video microscopy and semi‐automated optical heart analysis (SOHA). Our data suggest that overall, age‐dependent changes in heart function in old FOXO flies were significantly ameliorated relative to controls. Ubiquitin levels were measured by quantitative western blot analysis. Geriatric control flies displayed higher ubiquitin levels relative to FOXO, suggesting enhanced proteostasis contributes to improved heart function. Additionally, FOXO‐specific RNAi lines were used to further evaluate the effects of FOXO on cardiac function. These preliminary data indicate that knocking down FOXO expression with small interfering RNA can have detrimental effects on heart performance.
Grant Funding Source: APS, NSF IOS‐1238831