Intrinsically aggregation-prone proteins form amyloid-like aggregates and contribute to tissue aging in C. elegans

Abstract

Reduced protein homeostasis and increased protein instability is a common feature of aging. Yet it remains unclear whether protein instability is a cause of aging. In neurodegenerative diseases and amyloidoses, specific proteins self-assemble into amyloid fibrils and accumulate as pathological solid aggregates in a variety of tissues. More recently, widespread protein aggregation has been described during normal aging, in the absence of disease processes. Until now, an extensive characterization of the nature of agedependent protein aggregation and its consequences for aging has been lacking. Here, we show that agedependent aggregates are rapidly formed by newly synthesized proteins and contain amyloid-like structures similar to disease-associated protein aggregates. Moreover, we demonstrate that agedependent protein aggregation accelerates the functional decline of different tissues in C. elegans. Together, these finding reveal that the formation of amyloid aggregates is a generic problem of aging and likely to be an important target for strategies designed to maintain physiological functions in later stages of life.2 Introduction:

Age‐related neurodegenerative diseases

“…Intercellular conditions commonly associated with aging include elevated oxidative stress as well as increased concentrations of aggregate‐prone polypeptides (Finkel & Holbrook, ; Huang et al, ). A cellular component that is especially susceptible to such factors is stress granules (SGs; Alberti, Mateju, Mediani, & Carra, ; Lechler et al, ).…”

αS1-Casein-Loaded Proteo-liposomes as Potential Inhibitors in Amyloid Fibrillogenesis: In Vivo Effects on a C. elegans Model of Alzheimer’s Disease

“…SML1954), in 10 mM Tris-HCl buffer pH 8.0 for 2h at RT followed by 16 h destaining. 62 For microscopy analysis, animals were immobilized with 0.01% tetramisole hydrochloride, Sigma-Aldrich Inc. (cat. T1512), on 4% agar pads.…”

Pathologic polyglutamine aggregation begins with a self-poisoning polymer crystal

“…Amyloids are highly ordered protein aggregates with self-templating activity. This activity drives the progression of multiple incurable diseases of aging, such as Alzheimer's (Chiti and Dobson, 2017 ;Huang et al, 2019 ). Understanding how amyloids start, or nucleate, is therefore fundamental to preventing these diseases.…”