Knockdown of neuronal DAF-15/Raptor promotes healthy aging in C. elegans
Knockdown of neuronal DAF-15/Raptor promotes healthy aging in C. elegans
复制标题
DOI：
10.1016/j.jgg.2023.11.002
复制
发表时间：
2023
影响因子：
5.9
通讯作者：
Di Chen
中科院分区：
文献类型：
--
作者：
Xiao Zang;Qi Wang;Hanxin Zhang;Yiyan Zhang;Zi Wang;Zixing Wu;Di Chen
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 C. elegans. However, it has not been clear whether TORC1 perturbation affects aging in a spatiotemporal manner. Here we applied the auxin-inducible degradation (AID) tool to knockdown 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 kinase (AMPK) α catalytic subunit. Transcriptome profiling revealed that the neuronal DAF-15 knockdown promotes 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.
