ArticleGeroScience2017
A system to identify inhibitors of mTOR signaling using high-resolution growth analysis in Saccharomyces cerevisiae.
Article in GeroScience, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 24 citations in OpenAlex.
- An mTOR inhibitor discovery system using drug-sensitized yeast.GeroScience · 2025Article
- Taurine deficiency as a driver of aging.Science (New York, N.Y.) · 2023Article
- Deficiency of the RNA-binding protein Cth2 extends yeast replicative lifespan by alleviating its repressive effects on mitochondrial function.Cell reports · 2022Article
- Article
- Article
- The potential of rapalogs to enhance resilience against SARS-CoV-2 infection and reduce the severity of COVID-19.The lancet. Healthy longevity · 2021Review
- Review
- Lawsone, a 2-hydroxy-1,4-naphthoquinone from Lawsonia inermis (henna), produces mitochondrial dysfunctions and triggers mitophagy in Saccharomyces cerevisiae.Molecular biology reports · 2020Article
- Microvascular contributions to age-related macular degeneration (AMD): from mechanisms of choriocapillaris aging to novel interventions.GeroScience · 2019Review
- Age-dependent effects of caloric restriction on mTOR and ubiquitin-proteasome pathways in skeletal muscles.GeroScience · 2019Article
- Role of age-related alterations of the cerebral venous circulation in the pathogenesis of vascular cognitive impairment.American journal of physiology. Heart and circulatory physiology · 2019Review
- Running out of developmental program and selfish anti-aging: a new hypothesis explaining the aging process in primates.GeroScience · 2019Review
- Defining the impact of mutation accumulation on replicative lifespan in yeast using cancer-associated mutator phenotypes.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Advances and challenges in geroscience research: An update.Physiology international · 2018Review
- Nrf2 deficiency in aged mice exacerbates cellular senescence promoting cerebrovascular inflammation.GeroScience · 2018Article
- Genetic screen identifies adaptive aneuploidy as a key mediator of ER stress resistance in yeast.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Translational Geroscience: From invertebrate models to companion animal and human interventions.Translational medicine of aging · 2018Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
The mechanistic target of rapamycin (mTOR) is a central regulator of growth and proliferation and mTOR inhibition is a promising therapy for a variety of diseases and disorders. Inhibition of mTOR complex I (mTORC1) with rapamycin delays aging and increases healthy longevity in laboratory animals and is used clinically at high doses to prevent organ transplant rejection and to treat some forms of cancer. Clinical use of rapamycin is associated with several unwanted side effects, however, and several strategies are being taken to identify mTORC1 inhibitors with fewer side effects. We describe here a yeast-based growth assay that can be used to screen for novel inhibitors of mTORC1. By testing compounds using a wild-type strain and isogenic cells lacking either TOR1 or FPR1, we can resolve not only whether a compound is an inhibitor of mTORC1 but also whether the inhibitor acts through a mechanism similar to rapamycin by binding Fpr1. Using this assay, we show that rapamycin derivatives behave similarly to rapamycin, while caffeine and the ATP competitive inhibitors Torin 1 and GSK2126458 are mTORC1 inhibitors in yeast that act independently of Fpr1. Some mTOR inhibitors in mammalian cells do not inhibit mTORC1 in yeast, and several nutraceutical compounds were not found to specifically inhibit mTOR but resulted in a general inhibition of yeast growth. Our screening method holds promise as a means of effectively assaying drug libraries for mTOR-inhibitory molecules in vivo that may be adapted as novel treatments to fight diseases and extend healthy longevity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.