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Protein Homeostasis and Ageing in C. elegans

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Ageing: Lessons from C. elegans

Part of the book series: Healthy Ageing and Longevity ((HAL))

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Abstract

Understanding the molecular mechanism underlying ageing and age-related diseases is the best strategy to design therapies and interventions to effectively decrease ageing and age-related morbidity and mortality. A decline in proteome quality results in the accumulation of misfolded proteins that tend to aggregate in soluble or insoluble entities and has a negative impact on cell physiology. Protein aggregation has been considered a common hallmark of several neurodegenerative diseases and is also associated with normal ageing. Although it is still not clear how and why protein aggregation occurs, it seems that altered protein synthesis, folding, repair and degradation, commonly referred as protein homeostasis, play a central role in this process. As a consequence, modified proteins tend to form insoluble high molecular weight aggregates that actively influence cell metabolism, proteasomal activity and protein turnover. In some cases, protein aggregation may be beneficial by reducing proteotoxic effects of protein complexes. However, whether protein aggregates play a causal role in ageing phenotypes and lifespan remains to be determined, and this is one of the key goals of biomedical ageing research. C. elegans is proving to be a very useful model for studying the aggregation of human disease proteins. Although the significance of human protein aggregation in C. elegans as a model for protein homeostasis and disease is debatable, several potentially important models of proteotoxicity have been developed. In this chapter, I will describe the importance of studying normal C. elegans protein aggregation, and the relevance of worm models of conformational diseases to ageing and age-related disease research.

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Acknowledgements

I would like to thank Dr. Regina Brunauer for helpful reading and discussion. SA was supported by PROMEP UAM-PTC483.

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Authors and Affiliations

  1. Health Sciences Department, Metropolitan Autonomous University, Lerma, Estado de México, Mexico

    Silvestre Alavez

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  1. Silvestre Alavez
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Correspondence to Silvestre Alavez .

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  1. Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark

    Anders Olsen

  2. Department of Metabolics & Aging, The Scripps Research Institute - Scripps Florida, Jupiter, Florida, USA

    Matthew S. Gill

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Alavez, S. (2017). Protein Homeostasis and Ageing in C. elegans . In: Olsen, A., Gill, M. (eds) Ageing: Lessons from C. elegans. Healthy Ageing and Longevity. Springer, Cham. https://doi.org/10.1007/978-3-319-44703-2_12

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