Relationships between protein degradation, cellular senescence, and organismal aging

Abstract

Summary Aging is a major risk factor for many diseases. Recent studies have shown that age-related disruption of proteostasis leads to the accumulation of abnormal proteins and that dysfunction of the two major intracellular proteolytic pathways, the ubiquitin-proteasome pathway, and the autophagy-lysosome pathway, is largely responsible for this process. Conversely, it has been shown that activation of these proteolytic pathways may contribute to lifespan extension and suppression of pathological conditions, making it a promising intervention for anti-aging. This review provides an overview of the important role of intracellular protein degradation in aging and summarizes how the disruption of proteostasis is involved in age-related diseases.

Towards Healthy Longevity: Comprehensive Insights from Molecular Targets and Biomarkers to Biological Clocks

“…The results by Janssens et al [ 79 ] suggest that tanespimycin can be repurposed into a gerotherapeutic, and other inhibitors of Hsp90 like monorden are an attractive avenue of study [ 193 ]. Compounds that stabilize and activate the proteasome by improving substrate entry into the proteasome or allosteric agonists that enhance substrate binding are of particular interest to combat aging [ 194 ]. Candidate compounds for the activation of the proteasome are reviewed by Njomen and Tepe [ 195 ].…”