Proteostasis-associated aging: lessons from a Drosophila model
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Genes & Genomics https://doi.org/10.1007/s13258-020-01012-9
REVIEW
Proteostasis‑associated aging: lessons from a Drosophila model Garbin Yu1 · Seogang Hyun1 Received: 7 September 2020 / Accepted: 13 October 2020 © The Genetics Society of Korea 2020
Abstract 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. Keywords Proteostasis · Aging · Chaperone · Autophagy · Proteasome · Drosophila
Introduction hroughout the life of a cell, proteins are continuously synthesized and degraded. Since proteins are involved in several important processes as catalysts, structural components, and regulators of the cell cycle, protein homeostasis or proteostasis is essential for maintaining cellular function. Proteostasis refers to a process that maintains optimum protein functioning through coordinated synthesis, folding, conformational changes, and degradation. Many studies have demonstrated a link between proteostasis and aging. The loss of proteostasis is considered a hallmark of aging in C. elegans, D. melanogaster, and mammals, while improving proteostasis using chemical treatments or genetic modifications delays aging and increases lifespan (Ben-Zvi et al. 2009; Folgueras et al. 2018; Jantrapirom et al. 2018; Kaushik and Cuervo 2015; Schinaman et al. 2019). During its lifetime, a cell may experience oxidative, translational, or ER stress, which induces protein misfolding. Such misfolded proteins accumulate to form aggregates that contribute to aging and neurodegenerative diseases (Kaushik and Cuervo 2015a; Moloney * Seogang Hyun [email protected] 1
Department of Life Science, Chung-Ang University, 156‑756 Seoul, South Korea
et al. 2010; Taylor et al. 2002). To avoid proteotoxicity and sustain proteostasis, there are many mechanisms that recognize damaged proteins and repair or destroy those proteins. These mechanisms include chaperones and two major protein degradation systems, the ubiquitin-proteasome system (UPS) and autophagy system (Hipp et al. 2019; Kaushik and Cuervo 2
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