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Updated: Jan 4, 2026
Isolating Intestinal Stem Cells from Adult Drosophila Midguts by FACS to Study Stem Cell Behavior During Aging
Published on: December 16, 2014
The TORC1 inhibitor Nprl2 protects age-related digestive function in Drosophila
Junmeng Xi1,2,3, Jiadong Cai1,2,3, Yang Cheng1,2
1College of Bioscience and Biotechnology, Yangzhou University, Yangzhou, China.
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.
Insights
High target of rapamycin complex 1 (TORC1) activity accelerates aging in the digestive tract. Inhibiting TORC1 activity can rescue age-related digestive dysfunction and promote longevity in Drosophila.
Area of Science:
- Cellular and Molecular Biology
- Geroscience
- Developmental Biology
Background:
- Aging and age-related diseases are widespread biological phenomena.
- Inhibition of target of rapamycin complex 1 (TORC1) extends lifespan and delays aging in model organisms.
- The precise mechanisms linking TORC1 to aging are not fully understood.
Purpose of the Study:
- To investigate the role of increased TORC1 activity in age-related digestive dysfunction using a Drosophila model.
- To explore the impact of the nprl2 loss-of-function mutation on TORC1 signaling and gastrointestinal aging.
Main Methods:
- Utilized a loss-of-function mutation in the nprl2 gene in Drosophila melanogaster.
- Assessed lifespan, crop function, and midgut phenotypes in nprl2 mutant flies.
- Manipulated TORC1 activity to observe rescue effects on age-related digestive dysfunction.
Main Results:
- The nprl2 mutation reduced Drosophila lifespan and caused early-onset crop distension and food accumulation.
- Decreasing TORC1 activity rescued the observed digestive and crop contraction defects in nprl2 mutants.
- nprl2-mutant flies displayed accelerated midgut aging, including shortened gut length, increased stem cell proliferation, and metabolic dysfunction, all reversible by TORC1 inhibition.
Conclusions:
- Elevated TORC1 activity due to nprl2 mutation accelerates gastrointestinal tract aging in Drosophila.
- TORC1 signaling is a key promoter of digestive tract senescence.
- Targeting TORC1 activity may offer therapeutic strategies for age-related digestive disorders.
