Proteostasis-associated aging: lessons from a Drosophila model

As cells age, they lose their ability to properly fold proteins, maintain protein folding, and eliminate misfolded proteins, which leads to the accumulation of abnormal protein aggregates and loss of protein homeostasis (proteostasis). Loss of proteostasis can accelerate aging and the onset of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. Mechanisms exist to prevent the detrimental effects of abnormal proteins that incorporate chaperones, autophagy, and the ubiquitin-proteasome system. These mechanisms are evolutionarily conserved across various species. Therefore, the effect of impaired proteostasis on aging has been studied using model organisms that are appropriate for aging studies. In this review, we focus on the relationship between proteostasis and aging, and factors that affect proteostasis in Drosophila. The manipulation of proteostasis can alter lifespan, modulate neurotoxicity, and delay the onset of neurodegeneration, indicating that proteostasis may be a novel pharmacological target for the development of treatments for various age-associated diseases.

Automated summary

As cells age, their ability to fold proteins properly declines, leading to the accumulation of abnormal protein aggregates and accelerating aging and neurodegenerative diseases. Mechanisms like chaperones, autophagy, and ubiquitin-proteasome system can prevent the harmful effects of abnormal proteins. Manipulating proteostasis can influence lifespan, neurotoxicity, and delay neurodegeneration, suggesting it as a potential pharmacological target for age-related diseases.