The frequency of yeast [PSI+] prion formation is increased during chronological ageing

Abstract

Ageing involves a time-dependent decline in a variety of intracellular mechanisms and is associated with cellular senescence. This can be exacerbated by prion diseases which can occur in a sporadic manner, predominantly during the later stages of life. Prions are infectious, self-templating proteins responsible for several neurodegenerative diseases in mammals and several prion-forming proteins have been found in yeast. We show here that the frequency of formation of the yeast [PSI+] prion, which is the altered form of the Sup35 translation termination factor, is increased during chronological ageing. This increase is exacerbated in an atg1 mutant suggesting that autophagy normally acts to suppress age-related prion formation. We further show that cells which have switched to [PSI+] have improved viability during chronological ageing which requires active autophagy. [PSI+] stains show increased autophagic flux which correlates with increased viability and decreased levels of cellular protein aggregation. Taken together, our data indicate that the frequency of [PSI+] prion formation increases during yeast chronological ageing, and switching to the [PSI+] form can exert beneficial effects via the promotion of autophagic flux.

Keywords

• prion
• yeast
• chronological ageing
• autophagy