Protein homeostasis and aging

This chapter elaborates on the need for precise mechanisms to maintain protein homeostasis and reviews the main components of the quality control systems-chaperones and proteases-and how they change with age. Protein quality control and maintenance of proteome homeostasis are tightly interconnected to the cellular response to stress. Alterations in protein homeostasis underlie the basis of severe human diseases of very different characteristics for which aging is an aggravating factor. All these age-related diseases have in common the presence of deposits of toxic protein products in the respective affected tissue. There has been growing interest in trying to enhance the mechanisms that contribute to protein quality control as a possible antiaging intervention and as treatment for these age-related disorders. The potential of this intervention resides in its universal nature, because independent of the harmful agent or misbehaving protein all cells count on common mechanisms to respond to cellular stress and proteotoxicity. Keys to this protection are the components of the protein quality control-chaperones and the proteolytic systems. Better molecular characterization of each of these pathways and extensive genetic evidence supporting the idea that manipulations in essential components of these pathways result in changes in longevity and life span further support the applicability of modifications in the activity of these pathways to regulate aging. One of the most exciting outcomes of the various manipulations aimed at enhancing the activity of the quality control system is the fact that changes in the activity of only one of these mechanisms have a beneficial effect beyond that expected by correcting a single arm of this antistress response.