The involvement of stress granules in aging and aging‐associated diseases

Abstract

Stress granules (SGs) are nonmembrane assemblies formed in cells in response to stress conditions. SGs mainly contain untranslated mRNA and a variety of proteins. RNAs and scaffold proteins with intrinsically disordered regions or RNA‐binding domains are essential for the assembly of SGs, and multivalent macromolecular interactions among these components are thought to be the driving forces for SG assembly. The SG assembly process includes regulation through post‐translational modification and involvement of the cytoskeletal system. During aging, many intracellular bioprocesses become disrupted by factors such as cellular environmental changes, mitochondrial dysfunction, and decline in the protein quality control system. Such changes could lead to the formation of aberrant SGs, as well as alterations in their maintenance, disassembly, and clearance. These aberrant SGs might in turn promote aging and aging‐associated diseases. In this paper, we first review the latest progress on the molecular mechanisms underlying SG assembly and SG functioning under stress conditions. Then, we provide a detailed discussion of the relevance of SGs to aging and aging‐associated diseases.

Targeting stress granules: A novel therapeutic strategy for human diseases

“…2 ), including cancers, neurodegenerative diseases, viral infections and autoimmune disease, well-documented by elegant reviews [ [33] , [34] , [35] , [36] , [37] ]. SGs affect multiple pathways by intercepting and sequestering signalling components, such as RACK1 (p38/JNK signalling), TRAF2 (NF-κB signalling), Raptor (mTOR signalling) and RhoA/ROCK1 (Wnt signalling) [ [33] , [34] , [35] , [36] , [37] ]. When exposed to stress environments, cells may arrest the cell cycle and repair stress-induced damage, or proceed to apoptosis.…”

“…Aging is accompanied by many intracellular processes such as cellular metabolic change, mitochondrial dysfunction and abnormal protein quality control, which could result in disrupted protein homeostasis and the abnormal formation, maintenance, disassembly and clearance of SGs, consequently leading to chronic or pathological SGs [ 35 ]. These aberrant SGs may accelerate the aging process and aging-associated diseases.…”

Amyotrophic Lateral Sclerosis: Proteins, Proteostasis, Prions, and Promises

“…The authors conclude that mutated FUS is likely to be pathogenic through a gain-of-function effect, rather than through titrating WT-FUS from the nucleus. In future work, it would be interesting to assess whether the colocalization of FUS with stress granules can be initiated by stressors other than acute heat stress (Huelgas-Morales et al, 2016 ), such as oxidative stress (Vance et al, 2013 ) or in the context of aging (Cao et al, 2020 ). C elegans is an ideal model system to explore the biology of stress signaling during aging due to its short lifespan and ease of growth/maintenance (Olsen, 2006 ).…”

Voice perturbations under the stress overload in young individuals: phenotyping and suboptimal health as predictors for cascading pathologies

“…Stress overload, disturbed microcirculation, and accelerated ageing Individuals extensively exposed to imbalanced stress are strongly predisposed to accelerated ageingcorresponding mechanisms have been described [76][77][78]. Consequently, affected systems are hormonal regulation and immune system-both involved in longevity versus ageing with cascading related pathologies [79][80][81].…”