Xiao Zang, Qi Wang, Hanxin Zhang, Yiyan Zhang, Zi Wang, Zixing Wu, Di Chen
Journal of genetics and genomics = Yi chuan xue bao 2023 Nov 10The 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 Caenorhabditiselegans. However, it has not been clear whether TORC1 perturbation affects aging in a spatiotemporal manner. Here, we apply the auxin-inducible degradation 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 α catalytic subunit. Transcriptome profiling reveals 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. Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.
Xiao Zang, Qi Wang, Hanxin Zhang, Yiyan Zhang, Zi Wang, Zixing Wu, Di Chen. Knockdown of neuronal DAF-15/Raptor promotes healthy aging in C. elegans. Journal of genetics and genomics = Yi chuan xue bao. 2023 Nov 10
PMID: 37951302
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