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RICTOR regulates an interspecies crosstalk that influences longevity through a methionine cycle-mitophagy axis

Motwani S, Bhandari S, Chitkara S, Ujjainiya R, Ghosh P, Sengupta S, Mukhopadhyay A · 2026 · Nature Communications · Atlas ID MOT2026

What this study shows

In the worm C. elegans, loss of the mTORC2 component RICTOR (rict-1) extended lifespan and raised osmotic-stress tolerance only on vitamin B12-rich bacterial diets with optimal methionine. The benefit required two B12-dependent enzymes, METR-1 (methionine cycle) and MMCM-1 (propionate breakdown), and a rise in succinate that fragments mitochondria and switches on mitophagy, which the authors found indispensable for the longevity. Evidence is from one invertebrate species and genetic loss of function; it does not show that mTORC2 inhibition extends lifespan in mammals or humans.

Abstract

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Adaptive modulation of physiological traits in response to dietary fluctuations is essential for organismal fitness and is governed by complex gene-diet interactions that remain mechanistically unexplored. Here, we identify the conserved mTORC2 component RICTOR as a critical regulator of dietary plasticity in Caenorhabditis elegans. Loss of rict-1/RICTOR confers enhanced osmotic stress tolerance and longevity on vitamin B12-rich bacterial diets containing optimal methionine.

Read the full abstract on PubMed →

At a glance

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Evidence type A Animal model Marked A because it is an animal intervention or observation study measuring an organismal outcome (model: Caenorhabditis elegans: rict-1 (RICTOR, mTORC2) mutants on E. coli OP50 versus vitamin B12-rich Comamonas diets; metr-1 and mmcm-1 dependence; mitochondrial morphology, mitophagy, osmotic-stress and lifespan assays); the code names the system studied -- animal work can be rigorous and still not be human data.
Study type4 - Animal Study
Model systemCaenorhabditis elegans: rict-1 (RICTOR, mTORC2) mutants on E. coli OP50 versus vitamin B12-rich Comamonas diets; metr-1 and mmcm-1 dependence; mitochondrial morphology, mitophagy, osmotic-stress and lifespan assays
JournalNature Communications
Year2026
Peer reviewedYes
Record last updated2026-10-01
SourceDOI 10.1038/s41467-026-77722-7 · PMID 42967947 · Free full text (PMC13724747)

Where this study fits

How this study connects to the pathway map, open questions, people and other studies in the Atlas.

People in the Atlas

  • Simran Motwani first author · 1 study in the Atlas

    First author of the 2026 Nature Communications study on RICTOR, vitamin B12 diets and longevity in C. elegans.

  • Arnab Mukhopadhyay last author · 1 study in the Atlas

    Studies how diet and gene activity interact to set lifespan in the roundworm C. elegans; his 2026 paper links loss of the mTORC2 component RICTOR to longevity on vitamin B12-rich diets through the methionine cycle and mitophagy.

  • Shomit Sengupta 3 studies in the Atlas

    Showed that mTORC1 controls whether the liver makes ketone bodies during fasting, and now leads biology for drug discovery at a metabolic-disease biotech

More: 4 other authors

No profile yet: Bhandari S, Chitkara S, Ujjainiya R, Ghosh P

Related studies

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All 62 studies on Longevity

Topics

MitophagyLongevityRictormTORC2Methionine

Extracted findings

These fields were extracted from the paper with AI assistance and have not been checked against the source. Read them as a pointer into the paper, not as curated claims; where they disagree with the curated summary above, the curated summary stands.

Interventionrict-1 (RICTOR) loss of function; vitamin B12-rich bacterial diet
TargetmTORC2 (RICTOR), methionine cycle, mitophagy
ModelC. elegans
EffectLoss of rict-1 extends lifespan and osmotic-stress tolerance on B12-rich diets; requires METR-1, MMCM-1, succinate-driven mitochondrial fragmentation and mitophagy

Cite this paper

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Motwani, S., Bhandari, S., Chitkara, S., Ujjainiya, R., Ghosh, P., Sengupta, S., & Mukhopadhyay, A. (2026). RICTOR regulates an interspecies crosstalk that influences longevity through a methionine cycle-mitophagy axis. Nature Communications. https://doi.org/10.1038/s41467-026-77722-7

@article{MOT2026,
  author       = {Motwani, S. and Bhandari, S. and Chitkara, S. and Ujjainiya, R. and Ghosh, P. and Sengupta, S. and Mukhopadhyay, A.},
  title        = {{RICTOR regulates an interspecies crosstalk that influences longevity through a methionine cycle-mitophagy axis}},
  journal      = {Nature Communications},
  year         = {2026},
  doi          = {10.1038/s41467-026-77722-7},
  note         = {PMID: 42967947},
}

Cite this Atlas record

The record is the Atlas's own work — the evidence label, the extracted findings and the links. It is cited as part of the dataset, not as the paper. 

Barton, O. (2026). Oliver's mTOR Atlas (record MOT2026) [Data set]. https://mtor-atlas.org/study/MOT2026/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_MOT2026,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record MOT2026},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/MOT2026/},
  doi          = {10.5281/zenodo.22059963}
}
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