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Research Paper|Volume 11, Issue 21|pp 9811—9828

The TORC1 inhibitor Nprl2 protects age-related digestive function in Drosophila

Junmeng Xi1,2,3, Jiadong Cai1,2,3, Yang Cheng1,2, Yuanyuan Fu2, Wanhong Wei1, Zhenbo Zhang4, Ziheng Zhuang5, Yue Hao6, Mary A. Lilly7, Youheng Wei1,2,3
  • 1College of Bioscience and Biotechnology, Yangzhou University, Yangzhou, China
  • 2Joint International Research Laboratory of Agriculture and Agri-Product Safety, The Ministry of Education of China, Yangzhou University, Yangzhou, China
  • 3Institute of Reproduction and Metabolism, Yangzhou University, Yangzhou, China
  • 4Reproductive Medicine Center, Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
  • 5School of Pharmaceutical Engineering and Life Sciences, Changzhou University, Changzhou, China
  • 6Key Laboratory of Pollinating Insect Biology, Ministry of Agriculture, Beijing, China
  • 7Cell Biology and Neurobiology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
Received: August 18, 2019Accepted: October 28, 2019Published: November 11, 2019
https://doi.org/10.18632/aging.102428

Copyright © 2019 Xi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Aging and age-related diseases occur in almost all organisms. Recently, it was discovered that the inhibition of target of rapamycin complex 1 (TORC1), a conserved complex that mediates nutrient status and cell metabolism, can extend an individual’s lifespan and inhibit age-related diseases in many model organisms. However, the mechanism whereby TORC1 affects aging remains elusive. Here, we use a loss-of-function mutation in nprl2, a component of GATOR1 that mediates amino acid levels and inhibits TORC1 activity, to investigate the effect of increased TORC1 activity on the occurrence of age-related digestive dysfunction in Drosophila. We found that the nprl2 mutation decreased Drosophila lifespan. Furthermore, the nprl2 mutant had a distended crop, with food accumulation at an early age. Interestingly, the inappropriate food distribution and digestion along with decreased crop contraction in nprl2 mutant can be rescued by decreasing TORC1 activity. In addition, nprl2-mutant flies exhibited age-related phenotypes in the midgut, including short gut length, a high rate of intestinal stem cell proliferation, and metabolic dysfunction, which could be rescued by inhibiting TORC1 activity. Our findings showed that the gastrointestinal tract aging process is accelerated in nprl2-mutant flies, owing to high TORC1 activity, which suggested that TORC1 promotes digestive tract senescence.