title: The microRNA miR-34 modulates ageing and neurodegeneration in Drosophila.
abstract: Human neurodegenerative diseases have the temporal hallmark of afflicting the elderly                 population. Ageing is one of the most prominent factors to influence disease onset                 and progression, yet little is known about the molecular pathways                 that connect these processes. To understand this connection it is necessary to                 identify the pathways that functionally integrate ageing, chronic maintenance of the                 brain and modulation of neurodegenerative disease. MicroRNAs (miRNA) are emerging as                 critical factors in gene regulation during development; however, their role in                 adult-onset, age-associated processes is only beginning to be revealed. Here we                 report that the conserved miRNA miR-34 regulates age-associated events and long-term                 brain integrity in Drosophila, providing a molecular link between ageing and                 neurodegeneration. Fly mir-34 expression exhibits adult-onset, brain-enriched                 and age-modulated characteristics. Whereas mir-34 loss triggers a gene                 profile of accelerated brain ageing, late-onset brain degeneration and a                 catastrophic decline in survival, mir-34 upregulation extends median lifespan                 and mitigates neurodegeneration induced by human pathogenic polyglutamine disease                 protein. Some of the age-associated effects of miR-34 require adult-onset                 translational repression of Eip74EF, an essential ETS domain transcription                 factor involved in steroid hormone pathways. Our studies indicate that                 miRNA-dependent pathways may have an impact on adult-onset, age-associated events by                 silencing developmental genes that later have a deleterious influence on adult life                 cycle and disease, and highlight fly miR-34 as a key miRNA with a role in this                 process.
authors.affiliation: Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Nan
authors.initials: N
authors.lastname: Liu
authors.forename: Michael
authors.initials: M
authors.lastname: Landreh
authors.forename: Kajia
authors.initials: K
authors.lastname: Cao
authors.forename: Masashi
authors.initials: M
authors.lastname: Abe
authors.forename: Gert-Jan
authors.initials: GJ
authors.lastname: Hendriks
authors.forename: Jason R
authors.initials: JR
authors.lastname: Kennerdell
authors.forename: Yongqing
authors.initials: Y
authors.lastname: Zhu
authors.forename: Li-San
authors.initials: LS
authors.lastname: Wang
authors.forename: Nancy M
authors.initials: NM
authors.lastname: Bonini
mesh_terms: D000375:Aging / Q000235:genetics*; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D015536:Down-Regulation; D029721:Drosophila Proteins / Q000096:biosynthesis / Q000235:genetics; D004331:Drosophila melanogaster / Q000235:genetics* / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics*; D006358:Hot Temperature; D006801:Humans; D008136:Longevity / Q000235:genetics; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D009154:Mutation; D019636:Neurodegenerative Diseases / Q000235:genetics* / Q000473:pathology; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D016019:Survival Analysis; D013997:Time Factors; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D015854:Up-Regulation
chemical_list: D029721:Drosophila Proteins; C060408:Eip74EF protein, Drosophila; D035683:MicroRNAs; D012333:RNA, Messenger; D014157:Transcription Factors