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

Document Type

Article

Publication Date

2021

Keywords

proteostasis, protein aggregation, proteinopathy, aging, mitochondrial dysfunction, mutations, epigenetic changes

Digital Object Identifier (DOI)

https://doi.org/10.1134/S0006297921030056

Abstract

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.

Was this content written or created while at USF?

Yes

Citation / Publisher Attribution

Biochemistry (Moscow), v. 86, p. 275-289

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