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Longevity pathways and maintenance of the proteome: the role of autophagy and mitophagy during yeast ageing

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Resumo:Ageing is a complex and multi-factorial process that results in the progressive accumulation of molecular alterations that disrupt different cellular functions. The budding yeast Saccharomyces cerevisiae is an important model organism that has significantly contributed to the identification of conserved molecular and cellular determinants of ageing. The nutrient-sensing pathways are well-recognized modulators of longevity from yeast to mammals, but their downstream effectors and outcomes on different features of ageing process are still poorly understood. A hypothesis that is attracting increased interest is that one of the major functions of these “longevity pathways” is to contribute to the maintenance of the proteome during ageing. In support of this hypothesis, evidence shows that TOR/Sch9 and Ras/PKA pathways are important regulators of autophagy that in turn are essential for healthy cellular ageing. It is also well known that mitochondria homeostasis and function regulate lifespan, but how mitochondrial dynamics, mitophagy and biogenesis are regulated during ageing remains to be elucidated. This review describes recent findings that shed light on how longevity pathways and metabolic status impact maintenance of the proteome in both yeast ageing paradigms. These findings demonstrate that yeast remain a powerful model system for elucidating these relationships and their influence on ageing regulation.
Autores principais:Marques, Belém Sampaio
Outros Autores:Ludovico, Paula; Burhans, William C.
Assunto:Nutrient-sensing pathways Autophagy Mitophagy Chronological lifespan Replicative lifespan Ageing Yeast replicative lifespan ageing
Ano:2014
País:Portugal
Tipo de documento:artigo
Tipo de acesso:acesso restrito
Instituição associada:Universidade do Minho
Idioma:inglês
Origem:RepositóriUM - Universidade do Minho
Descrição
Resumo:Ageing is a complex and multi-factorial process that results in the progressive accumulation of molecular alterations that disrupt different cellular functions. The budding yeast Saccharomyces cerevisiae is an important model organism that has significantly contributed to the identification of conserved molecular and cellular determinants of ageing. The nutrient-sensing pathways are well-recognized modulators of longevity from yeast to mammals, but their downstream effectors and outcomes on different features of ageing process are still poorly understood. A hypothesis that is attracting increased interest is that one of the major functions of these “longevity pathways” is to contribute to the maintenance of the proteome during ageing. In support of this hypothesis, evidence shows that TOR/Sch9 and Ras/PKA pathways are important regulators of autophagy that in turn are essential for healthy cellular ageing. It is also well known that mitochondria homeostasis and function regulate lifespan, but how mitochondrial dynamics, mitophagy and biogenesis are regulated during ageing remains to be elucidated. This review describes recent findings that shed light on how longevity pathways and metabolic status impact maintenance of the proteome in both yeast ageing paradigms. These findings demonstrate that yeast remain a powerful model system for elucidating these relationships and their influence on ageing regulation.