Knockdown of neuronal DAF-15/Raptor promotes healthy aging in C.elegans  

作　　者：Xiao Zang Qi Wang Hanxin Zhang Yiyan Zhang Zi Wang Zixing Wu Di Chen 

机构地区：[1]Model Animal Research Center of Medical School,Nanjing University,Nanjing,Jiangsu 210061,China [2]Zhejiang University-University of Edinburgh Institute,School of Medicine,Zhejiang University,Haining,Zhejiang 314400,China [3]Department of Colorectal Surgery,The Second Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou,Zhejiang 310058,China

出　　处：《Journal of Genetics and Genomics》2024年第5期507-516,共10页遗传学报（英文版）

基　　金：the National Key R&D Program of China(2021YFA0805802 to D.C.);the National Natural Science Foundation of China(31971092 and 32171156 to D.C.);Some strains were provided by the Caenorhabditis Genetics Center(CGC),which is funded by NIHOffice of Research Infrastructure Programs(P40 OD010440).

摘　　要：The highly conserved target of rapamycin(TOR)pathway plays an important role in aging across species.Previous studies have established that inhibition of the TOR complex 1(TORC1)significantly extends lifespan in Caenorhabditis elegans.However,it has not been clear whether TORC1 perturbation affects aging in a spatiotemporal manner.Here,we apply the auxin-inducible degradation tool to knock down endogenous DAF-15,the C.elegans ortholog of regulatory associated protein of TOR(Raptor),to characterize its roles in aging.Global or tissue-specific inhibition of DAF-15 during development results in various growth defects,whereas neuron-specific knockdown of DAF-15 during adulthood significantly extends lifespan and healthspan.The neuronal DAF-15 deficiency-induced longevity requires the intestinal activities of DAF-16/FOXO and PHA-4/FOXA transcription factors,as well as the AAK-2/AMP-activated protein kinaseαcatalytic subunit.Transcriptome profiling reveals that the neuronal DAF-15 knockdown promotes the expression of genes involved in protection.These findings define the tissue-specific roles of TORC1 in healthy aging and highlight the importance of neuronal modulation of aging.

关 键 词：Aging targetof rapamycin DAF-15 DAF-16 C.elegans 

分 类 号：Q965[生物学—昆虫学]