On the Role of Normal Aging Processes in the Onset and Pathogenesis of Diseases Associated with the Abnormal Accumulation of Protein Aggregates

Aging is a prime systemic cause of various age-related diseases, in particular, proteinopathies. In fact, most diseases associated with protein misfolding are sporadic, and their incidence increases with aging. This review examines the process of protein aggregate formation, the toxicity of such agg...

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Bibliographic Details
Published in:Biochemistry (Moscow) 2021-03, Vol.86 (3), p.275-289
Main Authors: Ilyinsky, Nikolay S., Nesterov, Semen V., Shestoperova, Elizaveta I., Fonin, Alexander V., Uversky, Vladimir N., Gordeliy, Valentin I.
Format: Article
Language:English
Subjects:
Age related diseases
Aggregates
Aging
Analysis
Animals
Biochemistry
Biomedical and Life Sciences
Biomedicine
Bioorganic Chemistry
Genomes
Genomics
Humans
Life Sciences
Microbiology
Mitochondria
Mitochondria - metabolism
Mitochondria - pathology
Neurodegenerative Diseases - etiology
Neurodegenerative Diseases - metabolism
Neurodegenerative Diseases - physiopathology
Pathogenesis
Protein Aggregation, Pathological
Protein folding
Proteins
Proteostasis
Proteostasis Deficiencies - etiology
Proteostasis Deficiencies - metabolism
Proteostasis Deficiencies - physiopathology
Review
Signalling systems
Telecommunication systems
Toxicity
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Summary:Aging is a prime systemic cause of various age-related diseases, in particular, proteinopathies. In fact, most diseases associated with protein misfolding are sporadic, and their incidence increases with aging. This review examines the process of protein aggregate formation, the toxicity of such aggregates, the organization of cellular systems involved in proteostasis, and the impact of protein aggregates on important cellular processes leading to proteinopathies. We also analyze how manifestations of aging (mitochondrial dysfunction, dysfunction of signaling systems, changes in the genome and epigenome) facilitate pathogenesis of various proteinopathies either directly, by increasing the propensity of key proteins for aggregation, or indirectly, through dysregulation of stress responses. Such analysis might help in outlining approaches for treating proteinopathies and extending healthy longevity.
ISSN:0006-2979
1608-3040
DOI:10.1134/S0006297921030056