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SEMINAR: School of Human Sciences Seminar Series

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Today's date is Thursday, October 01, 2020
School of Human Sciences Seminar Series : Age-related pathway signatures relevance for treating ageing disorders Other events...
Abstract: Ageing occurs in a regulated manner and the associated gene expression changes could contribute to the onset of many diseases, either by creating a permissive environment for pathology, or by directly inducing these conditions. We identified an Age-related Gene Expression Signature (AGES) in rats, by studying a time course of gene expression throughout the lifespan of the animal. Examining multiple tissues in rats aged 6, 9, 12, 18, 21, 24 and 27 months, we demonstrated tissue-specific and common gene pathway changes. Since AGES were shared by multiple tissues, it is plausible that perturbation of a discrete cell signalling pathway can extend life span and delay age-related diseases. We next asked, what is the impact of clinically-relevant low doses of rapalog on age-related pathway changes? Rapamycin or rapalogs (e.g. RAD001) that are inhibitors of mTORC1 (mammalian target of rapamycin complex 1), have been shown to increase lifespan and forestall age-related phenotypes in multiple species, including humans. Interestingly, the effect of RAD001 on age-related gene pathways was more pronounced in kidneys compared with other examined tissues (liver, skeletal muscle and hippocampus). The majority of the age-related pathways in the kidney were counter-regulated by a low dose of RAD001, and this was accompanied by reduction of age-related renal histopathology. We also examined the impact of RAD001 on molecular pathways implicated in skeletal muscle ageing (sarcopenia). This partial inhibition of the mTORC1 pathway counteracted age-related changes in expression of several genes related to senescence, muscle atrophy and deterioration of neuromuscular junctions, plus prevented loss of muscle mass for select muscles. These studies emphasise the potential benefit of drugs that target global signalling pathways as a successful strategy to reduce the adverse consequences of ageing.
Speaker(s) Dr Tea Shavlakadze is an Investigator at Novartis (Cambridge, USA), where she leads a drug discovery program aimed at targeting pathways that create a permissive environment for age-related diseases, or directly induce these conditions. Discovery and perturbation of age-related signalling pathways to treat age-related diseases is the focus of her research.
Location Seminar Room 1.81, School of Human Science, Anatomy Building
Contact Christine Page <[email protected]> : 6488 7126
URL https://www.uwa.edu.au/science/schools/school-of-human-sciences
Start Tue, 03 Sep 2019 13:00
End Tue, 03 Sep 2019 14:00
Submitted by Christine Page <[email protected]>
Last Updated Tue, 27 Aug 2019 15:11
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