Proteasome modulation: A way to delay aging?

Abstract

The ability to maintain a functional proteome, or proteostasis, is challenged as aging progresses. Misfolded and damaged proteins accumulate with age, causing perturbations to cellular and tissue function that hallmarks a multitude of age-related diseases. The proteasome is one of the main cellular protein clearance mechanisms, is a key component of the proteostasis network and has a crucial role in cellular physiology. Proteasome function exhibits an age-related decline that has been correlated with the accumulation of protein aggregates and the progression of proteotoxic disorders. Strategies that may promote proteasome expression, assembly, or activity extend both cellular and organismal lifespan and delay the progression of late-onset pathologies. In this review, we discuss the links between proteasome dysfunction and aging as well as the different approaches that can induce proteasome expression/assembly/activity/function and their potential to decelerate aging and degenerative diseases. © 2019 Elsevier Inc. All rights reserved.