Matches in SemOpenAlex for { <https://semopenalex.org/work/W3124725380> ?p ?o ?g. }
- W3124725380 abstract "Abstract The identification and validation of drugs that promote health during aging (‘geroprotectors’) is key to the retardation or prevention of chronic age-related diseases. Here we found that most of the established pro-longevity compounds shown to extend lifespan in model organisms also alter extracellular matrix gene expression ( i.e., matrisome) in human cell lines. To harness this novel observation, we used age-stratified human transcriptomes to define the age-related matreotype, which represents the matrisome gene expression pattern associated with age. Using a ‘youthful’ matreotype, we screened in silico for geroprotective drug candidates. To validate drug candidates, we developed a novel tool using prolonged collagen expression as a non-invasive and in-vivo surrogate marker for C. elegans longevity. With this reporter, we were able to eliminate false positive drug candidates and determine the appropriate dose for extending the lifespan of C. elegans . We improved drug uptake for one of our predicted compounds, genistein, and reconciled previous contradictory reports of its effects on longevity. We identified and validated new compounds, tretinoin, chondroitin sulfate, and hyaluronic acid, for their ability to restore age-related decline of collagen homeostasis and increase lifespan. Thus, our innovative drug screening approach - employing extracellular matrix homeostasis - facilitates the discovery of pharmacological interventions promoting healthy aging. Highlights Many geroprotective drugs alter extracellular matrix gene expression Defined young and old human matreotype signatures can identify novel potential geroprotective compounds Prolonged collagen homeostasis as a surrogate marker for longevity" @default.
- W3124725380 created "2021-02-01" @default.
- W3124725380 creator A5009762865 @default.
- W3124725380 creator A5013725273 @default.
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- W3124725380 creator A5038692003 @default.
- W3124725380 creator A5041121259 @default.
- W3124725380 creator A5052679723 @default.
- W3124725380 creator A5080253914 @default.
- W3124725380 date "2021-01-27" @default.
- W3124725380 modified "2023-10-14" @default.
- W3124725380 title "Youthful and age-related matreotypes predict drugs promoting longevity" @default.
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- W3124725380 doi "https://doi.org/10.1101/2021.01.26.428242" @default.