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Updated: Aug 14, 2025
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Quantifying Tissue-Specific Proteostatic Decline in Caenorhabditis elegans
Published on: September 7, 2021
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Reduced sphingolipid biosynthesis modulates proteostasis networks to enhance longevity
Nathaniel L Hepowit1, Eric Blalock2, Sangderk Lee3
1Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN 37240, USA.
Aging
|January 14, 2023
Summary
Myriocin drug treatment extends lifespan by impacting sphingolipid synthesis and amino acid pools. This study reveals a novel role for ubiquitin in promoting longevity through amino acid transporter regulation.
Area of Science:
- Gerontology and Molecular Biology
- Cellular Aging Mechanisms
- Pharmacological Interventions for Longevity
Background:
- The growing elderly population presents challenges due to age-associated diseases.
- Nutrient restriction is known to slow aging and improve health but is difficult to practice.
- Pharmacological strategies, like myriocin, are being explored to mimic health benefits of nutrient restriction.
Purpose of the Study:
- To investigate the cellular response to myriocin during the initial 6 hours of treatment.
- To elucidate the role of ubiquitin in myriocin-mediated lifespan extension.
- To understand the novel mechanisms by which myriocin impacts cellular processes related to aging.
Main Methods:
- Transcriptomic analysis of yeast cells treated with myriocin.
- Investigating the function of the methionine transporter Mup1 under myriocin treatment.
- Assessing the impact of the stressed-induced ubiquitin gene UBI4 on lifespan.
- Analyzing the effect of fusing Mup1 with a deubiquitinase domain on longevity.
Main Results:
- Myriocin treatment leads to lowered amino acid pools, promoting a quiescent, long-lived state.
- The stressed-induced ubiquitin gene UBI4 is essential for myriocin-enhanced lifespan.
- Mup1 transporter activity is impaired, and it undergoes endocytic clearance in myriocin-treated cells.
- Myriocin treatment significantly increases K63-linked ubiquitin polymers, indicating broader effects on ubiquitination.
Conclusions:
- Ubiquitination of amino acid transporters plays a novel role in promoting longevity in myriocin-treated yeast.
- UBI4 and specific ubiquitination patterns are critical for the lifespan-extending effects of myriocin.
- Targeting ubiquitination and deubiquitination pathways may offer new strategies for promoting healthy aging.
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