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Impact of genetic background and experimental reproducibility on identifying chemical compounds with robust longevity effects.
- Source :
-
Nature communications [Nat Commun] 2017 Feb 21; Vol. 8, pp. 14256. Date of Electronic Publication: 2017 Feb 21. - Publication Year :
- 2017
-
Abstract
- Limiting the debilitating consequences of ageing is a major medical challenge of our time. Robust pharmacological interventions that promote healthy ageing across diverse genetic backgrounds may engage conserved longevity pathways. Here we report results from the Caenorhabditis Intervention Testing Program in assessing longevity variation across 22 Caenorhabditis strains spanning 3 species, using multiple replicates collected across three independent laboratories. Reproducibility between test sites is high, whereas individual trial reproducibility is relatively low. Of ten pro-longevity chemicals tested, six significantly extend lifespan in at least one strain. Three reported dietary restriction mimetics are mainly effective across C. elegans strains, indicating species and strain-specific responses. In contrast, the amyloid dye ThioflavinT is both potent and robust across the strains. Our results highlight promising pharmacological leads and demonstrate the importance of assessing lifespans of discrete cohorts across repeat studies to capture biological variation in the search for reproducible ageing interventions.
- Subjects :
- Animals
Benzothiazoles
Caenorhabditis classification
Caenorhabditis genetics
Caenorhabditis elegans drug effects
Caenorhabditis elegans genetics
Dose-Response Relationship, Drug
Fertility drug effects
Fertility genetics
Longevity genetics
Reproducibility of Results
Species Specificity
Thiazoles pharmacology
Caenorhabditis drug effects
Genetic Background
Longevity drug effects
Organic Chemicals pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 8
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 28220799
- Full Text :
- https://doi.org/10.1038/ncomms14256