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

Xiao Zang; Qi Wang; Hanxin Zhang; Yiyan Zhang; Zi Wang; Zixing Wu; Di Chen

doi:10.1016/j.jgg.2023.11.002

Volume 51 Issue 5

May 2024

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Article Navigation > Journal of Genetics and Genomics > 2024 > 51(5): 507-516

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

doi: 10.1016/j.jgg.2023.11.002

Xiao Zang^a,b,
Qi Wang^a,b,
Hanxin Zhang^a,
Yiyan Zhang^a,b,
Zi Wang^a,
Zixing Wu^a,
Di Chen^a,b,c

a. Model Animal Research Center of Medical School, Nanjing University, Nanjing, Jiangsu 210061, China;
b. Zhejiang University-University of Edinburgh Institute, School of Medicine, Zhejiang University, Haining, Zhejiang 314400, China;
c. Department of Colorectal Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China

Funds:

D Program of China (2021YFA0805802 to D. C.), and 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 NIH Office of Research Infrastructure Programs (P40 OD010440).

We thank Drs. Qian Bian, Mei Ding, Mengqiu Dong, Zhuo Du, Lingfeng Meng, Billy Qi, Ye Tian, Suhong Xu, and Wei Zou for reagents and discussions. This work was supported by grants from the National Key R&

Received Date: 2023-07-07
Accepted Date: 2023-11-06
Rev Recd Date: 2023-11-06

Available Online: 2025-06-06

Publish Date: 2023-11-10

Abstract

Abstract

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 kinase α catalytic 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.
- Aging,
- target of rapamycin,
- DAF-15,
- DAF-16,
- C. elegans

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References(74)

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