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RNA Polymerase III in healthy ageing: Consolidating the mechanisms of longevity from worms and flies to mice.


The proportion of older individuals is steadily increasing in our societies. Since age is the main risk factor for a number of debilitating, chronic diseases and comorbidities, this demographic change is resulting in ever-increasing human and socioeconomic costs. Understanding the biology of ageing is a key research priority because it has the potential to provide us with means to maintain health into old age. Research in biogerontology has firmly shown that animal ageing is modifiable by identifying a suite of nutritional, genetic and pharmacological interventions capable of extending lifespan and improving health in older ages. The beneficial effects of these interventions are strongly conserved between animal species. Down-regulation of nutrient sensing signalling pathways, such as those governed by the Target of Rapamycin kinase Complex 1 (TORC1) either by genetic or pharmacological means, is an excellent example of this: its health and survival benefits can be observed in species ranging from worms to mice. However, we still do not have a full understanding of the processes that drive ageing, and this knowledge is necessary if we are to design treatments capable of improving late-life health and wellbeing in humans. We have recently shown that partially inhibiting the evolutionarily conserved enzyme, RNA polymerase III (Pol III), can extend lifespan in yeast, worms and flies. Importantly, Pol III inhibition can recapitulate the effect of systemic TORC1 inhibition on lifespan, revealing Pol III as a key mechanism driving ageing downstream of TORC1. Pol III is one of three RNA polymerases functioning in the eukaryotic nucleus. Historical focus on protein coding genes, solely transcribed by Pol II, has left the roles of Pol III relatively unexplored despite its fundamental cellular function. Here, we propose to pursue our efforts to understand the role of this understudied enzyme in the biology of ageing.

Project completion date : 2023-06-30 12:00:00

Major organization : UNIVERSITY OF KENT

Address : Giles Ln, Canterbury CT2 7NZ

Country :United Kingdom

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Publication:Mena Report
Date:Jul 3, 2019
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