Protein Aggregation Increases with Age 英文参考文献.docVIP

Synopsis ProteinAggregationIncreaseswithAge RachelJones* FreelanceScienceWriterandEditor,Welwyn,Hertfordshire,UnitedKingdom Aggregation (‘‘clumping together’’) of certain cellular proteins is a common feature of a variety of diseases including neurodegenerativeconditionssuchasPar- kinson’s, Alzheimer’s, and Huntington’s diseases. Many of these conditions are moreprevalentinoldage,butthechanges that cause increased aggregation of these diseaseproteinsarenotwellunderstood. A new study by Cynthia Kenyon and colleagues shows that aging in the nema- todeCaenorhabditiselegansisassociatedwith increasedaggregationofalargenumberof proteins, even in the apparent absence of incidenceofprotein-aggregationdiseasesin oldageandthepropensityforalargesubset ofproteinstobecomemoreinsolublewith age.Toinvestigatetheassociationofaging with protein aggregation, the authors looked at worms bearing a mutation in the insulin/IGF-1 (insulin-likegrowthfac- tor 1) signalling pathway that doubles the lifespan of the animals and also delays progressionin C.elegans models ofprotein aggregationdiseases.Althoughyoungani- mals with this mutation showed the same levels of insoluble proteins as young wild- typewormsdid,therewasamuchsmaller increase in insoluble proteins in older animalswiththemutation. Severalhundredproteinsbecamehighly insoluble with age in the worm. One of theproteinsdetectedbymassspectrom- etry, KIN-19, shown in the figure, forms aggregatesinthepharynxwithage. doi:10.1371/journal.pbio.1000449.g001 disease. Many of these proteins are encoded by genes that influence lifespan or aggregation of proteins with repeated polyglutamine sequences (the aggregation motifinvolvedinHuntington’sdiseaseand otherconditions),suggestingthatanaging- associated increasein proteinaggregation might affect both lifespan and neurode- generation. Whentheauthorscomparedtheaggre- gation-prone set of proteins with the C. elegans proteome as a whole, they found thatproteinswhoseinhibitioncanincrease lifes