Descrizione del progetto
Una piattaforma per la valutazione di farmaci anti-invecchiamento basati su cellule
L’invecchiamento della popolazione, insieme alle malattie legate all’età, rende sempre più importante la ricerca sull’invecchiamento. In precedenza, il gruppo di ricerca di questo progetto ha realizzato l’orologio epigenetico CellAge, basato sulla metilazione del DNA e in grado di rilevare con precisione impercettibili cambiamenti legati all’invecchiamento nelle cellule primarie in vitro degli esseri umani in seguito a una breve terapia farmacologica anti-invecchiamento a base di rapamicina e trametinib. Il progetto AgePhagy, finanziato dall’UE, provvederà ora a collegare l’orologio CellAge alla propria banca dati di farmaci per l’autofagia, allo scopo di testare la fattibilità commerciale di questa piattaforma per la valutazione dei farmaci anti-invecchiamento. Ai fini di un’ulteriore convalida dell’orologio quale biomarcatore attendibile dell’invecchiamento umano, il team combinerà i suoi risultati con test di longevità in vivo nella Drosophila. L’esito finale sarà un’innovativa piattaforma accelerata per la scoperta di farmaci anti-invecchiamento.
Obiettivo
The steeply increasing ageing population, and accompanying rise of age-related diseases will soon have profound societal and economic effects, making ageing research increasingly important and outcome of this grant impactful. Our most promising way to improve health in the elderly is by replicating decades of genetic finding in model organisms of healthy long-lived mutants to pharmacological approaches. This will enable transition of these findings to clinical trials. In the CancerPhagy project, we showed that genetic upregulation of autophagy, major cellular degradation pathway, increased lifespan, which we aim to mimic by pharmacological treatment. To this end, we developed the CellAge epigenetic clock, which is based on DNA methylation and which is the first clock that accurately detects subtle ageing changes in human primary cells in vitro upon a short anti-ageing drugs treatment, as shown using rapamycin and trametinib. This differentiates our clock from other available epigenetic clocks which are designed to accurately determine human age in years. By connecting the CellAge clock to autophagy drug library we will test the commercial viability of our anti-ageing drug assessment platform. To further validate our CellAge clock as a robust human ageing biomarker, we will combine its outputs with longevity assays in vivo in Drosophila. The final outcome will be an innovative and accelerated discovery platform for sought after anti-ageing/geroprotector drugs, which we will in this first instance test autophagy modifier drugs. Throughout the project we will closely collaborate with our industrial collaborator, GSK and UCL Business, which will assure we maximise the potential of our platform. Our ultimate goal is to uncover novel autophagy modifiers with anti-ageing properties and to launch the CellAge clock as the most advanced platform for expedited discovery of anti-ageing compounds.
Campo scientifico
Programma(i)
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Meccanismo di finanziamento
ERC-POC - Proof of Concept GrantIstituzione ospitante
WC1E 6BT London
Regno Unito