ArticleExperimental gerontology2009
A forward genetic screen in Drosophila implicates insulin signaling in age-related locomotor impairment.
Article in Experimental gerontology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Natural variation in age-related dopamine neuron degeneration is glutathione dependent and linked to life span.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Translational relevance of forward genetic screens in animal models for the study of psychiatric disease.Neuroscience and biobehavioral reviews · 2022Review
- Alcohol sedation in adultCommunications biology · 2019Article
- Review
- Pervasive Behavioral Effects of MicroRNA Regulation inGenetics · 2017Article
- Behavioral Senescence and Aging-Related Changes in Motor Neurons and Brain Neuromodulator Levels Are Ameliorated by Lifespan-Extending Reproductive Dormancy inFrontiers in cellular neuroscience · 2017Article
- The Drosophila insulin receptor independently modulates lifespan and locomotor senescence.PloS one · 2015Article
- Developmental ethanol exposure leads to dysregulation of lipid metabolism and oxidative stress in Drosophila.G3 (Bethesda, Md.) · 2014Article
- Genetic studies in Drosophila and humans support a model for the concerted function of CISD2, PPT1 and CLN3 in disease.Biology open · 2014Article
- Factors that regulate insulin producing cells and their output in Drosophila.Frontiers in physiology · 2013Review
- Genomic basis of aging and life-history evolution in Drosophila melanogaster.Evolution; international journal of organic evolution · 2012Article
- Chloride intracellular channels modulate acute ethanol behaviors in Drosophila, Caenorhabditis elegans and mice.Genes, brain, and behavior · 2012Article
- Identification of mutations that delay somatic or reproductive aging of Caenorhabditis elegans.Genetics · 2011Article
- Drosophila as a model for age-related impairment in locomotor and other behaviors.Experimental gerontology · 2011Review
- Ageing in Drosophila: the role of the insulin/Igf and TOR signalling network.Experimental gerontology · 2011Review
- Insulin/IGF-I and related signaling pathways regulate aging in nondividing cells: from yeast to the mammalian brain.TheScientificWorldJournal · 2010Review
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6 authors.
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Abstract
Age-related locomotor impairment (ARLI) is one of the most detrimental changes that occurs during aging. Elderly individuals with ARLI are at increased risks for falls, depression and a number of other co-morbidities. Despite its clinical significance, little is known about the genes that influence ARLI. We consequently performed a forward genetic screen to identify Drosophila strains with delayed ARLI using negative geotaxis as an index of locomotor function. One of the delayed ARLI strains recovered from the screen had a P-element insertion that decreased expression of the insulin signaling gene phosphoinositide-dependent kinase 1 (PDK1) Precise excision of the P-element insertion reverted PDK1 expression and ARLI to the same as control flies, indicating that disruption of PDK1 leads to delayed ARLI. Follow-up studies showed that additional loss of function mutations in PDK1 as well as loss of function alleles of two other insulin signaling genes, Dp110 and Akt (the genes for the catalytic subunit of phosphoinositide 3-kinase and AKT), also forestalled ARLI. Interestingly, only some of the strains with delayed ARLI had elevated resistance to paraquat, indicating that enhanced resistance to this oxidative stressor is not required for preservation of locomotor function across age. Our studies implicate insulin signaling as a key regulator of ARLI in Drosophila.
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