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Surveying Low-Cost Methods to Measure Lifespan and Healthspan in Caenorhabditis elegans
Published on: May 18, 2022
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mTORC2-SGK-1 acts in two environmentally responsive pathways with opposing effects on longevity
Masaki Mizunuma1, Elke Neumann-Haefelin, Natalie Moroz
1Joslin Diabetes Center, Harvard Stem Cell Institute, Harvard Medical School Department of Genetics, Boston, MA, 02215, USA; Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima, 739-8530, Japan.
Aging Cell
|July 22, 2014
Summary
The mechanistic target of rapamycin complex 2 (mTORC2) impacts aging in C. elegans through two opposing pathways. Bacterial food signals and temperature influence whether mTORC2 promotes or limits lifespan.
Area of Science:
- Molecular Biology
- Gerontology
- Genetics
Background:
- The mechanistic target of rapamycin (mTOR) kinase, existing in mTORC1 and mTORC2 complexes, is crucial for regulating growth, disease, and aging.
- While mTORC1 inhibition is known to extend lifespan across eukaryotes, the role of mTORC2 in aging, particularly its interaction with the bacterial food source in C. elegans, is less understood.
- Conflicting data exists regarding the influence of the SGK-1 kinase, regulated by mTORC2, on C. elegans lifespan.
Purpose of the Study:
- To investigate the complex role of mTORC2 in modulating longevity in Caenorhabditis elegans.
- To elucidate how the mTORC2 component Rictor (RICT-1) and its downstream kinase SGK-1 influence aging through distinct pathways.
- To reconcile conflicting data on SGK-1 and aging and understand the impact of the bacterial microenvironment on mTORC2-mediated aging.
Main Methods:
- Analysis of the mTORC2 component Rictor (RICT-1) in Caenorhabditis elegans.
- Investigating the interaction between RICT-1, SGK-1, and the transcription factor SKN-1/Nrf in different tissues (intestine and neurons).
- Examining the influence of bacterial food sources and temperature on these pathways and their effect on lifespan.
Main Results:
- mTORC2, via RICT-1, modulates longevity by activating SGK-1 in two pathways with opposing effects on lifespan.
- In the intestine, RICT-1/mTORC2 limits longevity by promoting SGK-1-mediated inhibition of SKN-1/Nrf, with this effect being dependent on bacterial food signals.
- In neurons, RICT-1/mTORC2 activates an SGK-1-dependent pathway that extends lifespan, particularly at lower temperatures.
Conclusions:
- mTORC2 and SGK-1 can either promote or accelerate aging depending on their specific cellular context and environmental cues.
- The bacterial microenvironment significantly influences SKN-1/Nrf activity, mTORC2 function, and overall aging in C. elegans.
- Identified two novel longevity-related functions of mTORC2 involving SGK-1-regulated responses to environmental factors, reconciling previous findings on SGK-1 and aging.
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