Abstract
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.
Highlights
Ageing is a complex and multi-factorial biological process driven by genetic, environmental and stochastic factors that lead to cellular degeneration and the progressive decline of multiple physiological functions
Deletion of SNF1 results in shortening of chronological lifespan (CLS) [44], a phenotype that was hypothesized to be related to the role of Snf1 in promoting respiration and autophagy [45, 46]. These findings suggest that in contrast to its detrimental effect in replicative lifespan (RLS), Snf1 could be necessary for fitness during CLS, which is a phenotype resembling the promoting effects of AMPK activation under caloric restriction (CR) in metazoans [47,48,49]
Our previous studies have shown that in CLS measurements made under conditions of proteotoxic stress, Sir2 is an important regulator of the transcription of ATG32 encoding a mitochondrial protein that confers selectivity during mitophagy [57]
Summary
Ageing is a complex and multi-factorial biological process driven by genetic, environmental and stochastic factors that lead to cellular degeneration and the progressive decline of multiple physiological functions. 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. A reduction in the activity of two nutrient-sensing pathways, the target of rapamycin (TOR)/the serine-threonine kinase Sch9 [5, 6] and the Ras/protein kinase A (PKA) [7, 8], can extend the two types of yeast lifespans.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
