A High-Throughput Screen for Yeast Replicative Lifespan Identifies Lifespan-Extending Compounds

Progress in aging research is constrained by the time requirement of measuring lifespans. Even the most rapid model for eukaryotic aging, the replicative lifespan of Saccharomyces cerevisiae, is technically limited to only several lifespan measurements each day. Here we report a 384-well plate-based...

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Main Authors: Ethan A. Sarnoski, Ping Liu, Murat Acar
Format: Article
Language:English
Published: Elsevier 2017-11-01
Series:Cell Reports
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124717316054
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author Ethan A. Sarnoski
Ping Liu
Murat Acar
author_facet Ethan A. Sarnoski
Ping Liu
Murat Acar
author_sort Ethan A. Sarnoski
collection DOAJ
description Progress in aging research is constrained by the time requirement of measuring lifespans. Even the most rapid model for eukaryotic aging, the replicative lifespan of Saccharomyces cerevisiae, is technically limited to only several lifespan measurements each day. Here we report a 384-well plate-based technique to measure replicative lifespan, termed High-Life. Using the High-Life technique, a single researcher can compare lifespan for more than 1,000 conditions per day. We validated the technique with long-lived mutant strains and the lifespan-extending compound ibuprofen. We also applied this technique to screen a small compound library for lifespan extension. Two hits, terreic acid and mycophenolic acid, were validated on our single-cell replicator device and found to extend mean replicative lifespan by 15% and 20%, respectively. Together, we report a technique for high-throughput lifespan measurement, and we identify two lifespan-extending compounds. Our technique could be used to efficiently drive early-stage discovery of pro-longevity therapeutics.
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spelling doaj.art-d4aa2849936349cc8368e26d19c617e22022-12-21T17:57:00ZengElsevierCell Reports2211-12472017-11-012192639264610.1016/j.celrep.2017.11.002A High-Throughput Screen for Yeast Replicative Lifespan Identifies Lifespan-Extending CompoundsEthan A. Sarnoski0Ping Liu1Murat Acar2Department of Molecular Cellular and Developmental Biology, Yale University, 219 Prospect Street, New Haven, CT 06511, USADepartment of Molecular Cellular and Developmental Biology, Yale University, 219 Prospect Street, New Haven, CT 06511, USADepartment of Molecular Cellular and Developmental Biology, Yale University, 219 Prospect Street, New Haven, CT 06511, USAProgress in aging research is constrained by the time requirement of measuring lifespans. Even the most rapid model for eukaryotic aging, the replicative lifespan of Saccharomyces cerevisiae, is technically limited to only several lifespan measurements each day. Here we report a 384-well plate-based technique to measure replicative lifespan, termed High-Life. Using the High-Life technique, a single researcher can compare lifespan for more than 1,000 conditions per day. We validated the technique with long-lived mutant strains and the lifespan-extending compound ibuprofen. We also applied this technique to screen a small compound library for lifespan extension. Two hits, terreic acid and mycophenolic acid, were validated on our single-cell replicator device and found to extend mean replicative lifespan by 15% and 20%, respectively. Together, we report a technique for high-throughput lifespan measurement, and we identify two lifespan-extending compounds. Our technique could be used to efficiently drive early-stage discovery of pro-longevity therapeutics.http://www.sciencedirect.com/science/article/pii/S2211124717316054agingreplicative lifespanSaccharomyces cerevisiaehigh-throughputcompound delivery
spellingShingle Ethan A. Sarnoski
Ping Liu
Murat Acar
A High-Throughput Screen for Yeast Replicative Lifespan Identifies Lifespan-Extending Compounds
Cell Reports
aging
replicative lifespan
Saccharomyces cerevisiae
high-throughput
compound delivery
title A High-Throughput Screen for Yeast Replicative Lifespan Identifies Lifespan-Extending Compounds
title_full A High-Throughput Screen for Yeast Replicative Lifespan Identifies Lifespan-Extending Compounds
title_fullStr A High-Throughput Screen for Yeast Replicative Lifespan Identifies Lifespan-Extending Compounds
title_full_unstemmed A High-Throughput Screen for Yeast Replicative Lifespan Identifies Lifespan-Extending Compounds
title_short A High-Throughput Screen for Yeast Replicative Lifespan Identifies Lifespan-Extending Compounds
title_sort high throughput screen for yeast replicative lifespan identifies lifespan extending compounds
topic aging
replicative lifespan
Saccharomyces cerevisiae
high-throughput
compound delivery
url http://www.sciencedirect.com/science/article/pii/S2211124717316054
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