Aging and protein homeostasis

Published on June 30, 2016 Reviewed on June 13, 2023   47 min

Other Talks in the Series: Autophagy and Lysosomal Storage Diseases

Other Talks in the Series: Aging

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My name is Ana Maria Cuervo, and I am a professor at the Albert Einstein College of Medicine and Co-Director of the Aging Center. I will be talking today about Protein Homeostasis and its importance in aging.
As all of you know, all proteins in the cells are continuously exposed to damaging agents that can modify their protein confirmation. So when a protein is damaged, it exposes regions that are going to be particularly hydrophobic or sticky, and can abnormally interact with other proteins in the cell. To avoid that, cells count on systems that take care of protein misfolding. The first ones are chaperones that if possible will refold these proteins to return to their normal conformation. And the second system are the proteases, where chaperones deliver the unfolded protein to undergo degradation. This is actually a very conservative system because when proteins breakdown into amino acids, they can be reutilized to sustain protein synthesis. So this quality control mechanisms, chaperones and proteases are in place and functioning in all the cells when we are young. However, as we get old and in particular diseases, these systems do not work properly and result in protein toxicity or accumulation of protein damage. For example, if chaperones cannot identify, they unfold the protein or if the proteolytic systems are not ready to receive this unfolded proteins, they will accumulate inside the cell and they will organize in higher molecular weight as structures in the form of protein aggregates or oligomers that are toxic for the cell. So in this lecture, I will give you some examples of what is known about chaperone and proteolytic systems malfunctioning during aging and how can they contribute to some of the characteristics of the phenotype of ageing.