title: Genes Related to Fatty Acid β-Oxidation Play a Role in the Functional Decline of the Drosophila Brain with Age.
abstract: In living organisms, ageing is widely considered to be the result of a multifaceted process consisting of the progressive accumulation of damage over time, having implications both in terms of function and survival. The study of ageing presents several challenges, from the different mechanisms implicated to the great diversity of systems affected over time. In the current study, we set out to identify genes involved in the functional decline of the brain with age and study its relevance in a tissue dependent manner using Drosophila melanogaster as a model system. Here we report the age-dependent upregulation of genes involved in the metabolic process of fatty acid β-oxidation in the nervous tissue of female wild-type flies. Downregulation of CG10814, dHNF4 and lipid mobilizing genes bmm and dAkh rescues the functional decline of the brain with age, both at the cellular and behaviour level, while over-expression worsens performance. Our data proposes the occurrence of a metabolic alteration in the fly brain with age, whereby the process of β-oxidation of fatty acids experiences a genetic gain-of-function. This event proved to be one of the main causes contributing to the functional decline of the brain with age.
authors: Center for Human Genetics, VIB-Center for the Biology of Disease, University of Leuven, 3000, Leuven, Belgium.
authors: António
authors: A
authors: Laranjeira
authors: Center for Human Genetics, VIB-Center for the Biology of Disease, University of Leuven, 3000, Leuven, Belgium.
authors: Joachim
authors: J
authors: Schulz
authors: Centro Biologia Molecular "Severo Ochoa", CSIC-UAM, Campus Universidad Autonoma de Madrid, 28049, Madrid, Spain.
authors: Carlos G
authors: CG
authors: Dotti
mesh_terms: D000375:Aging / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D002940:Circadian Rhythm; D029721:Drosophila Proteins / Q000235:genetics*; D004331:Drosophila melanogaster / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D005227:Fatty Acids / Q000737:chemistry*; D005260:Female; D005820:Genetic Testing; D008066:Lipolysis; D008136:Longevity / Q000235:genetics*; D010084:Oxidation-Reduction; D018384:Oxidative Stress
chemical_list: D029721:Drosophila Proteins; D005227:Fatty Acids