RNA dysregulation as a determinant of aging and neurodegenerative vulnerability.

Sawyer Randles, Gene W Yeo

Biological Sciences Graduate Program, University of California San Diego, La Jolla, CA, USA; Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA; Sanford Laboratories for Innovative Medicines, San Diego, CA, USA.Biological Sciences Graduate Program, University of California San Diego, La Jolla, CA, USA; Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA; Sanford Laboratories for Innovative Medicines, San Diego, CA, USA. · pubmed

Paper

Abstract

In the nervous system, aging causes deterioration of cellular and molecular processes that are associated with declines in cognition, sensory perception, and motor coordination. Aging is also the strongest risk factor for neurodegenerative disease, yet the mechanisms by which aging predisposes neurons to dysfunction remain incompletely understood. While genomic instability, proteostasis decline, mitochondrial dysfunction, and chronic inflammation have dominated prevailing models, recent evidence highlights RNA dysregulation as a central component of age-associated decline. In this review, we summarize recent findings suggesting that aging progressively erodes RNA regulatory fidelity through alterations in RNA-binding protein abundance, localization, biophysical behavior, and RNA interactions. We argue that age-dependent RNA dysregulation represents an important mechanism that converges with genetic risk to drive neuronal vulnerability and neurodegeneration.

The following analysis is generated by AI and may contain errors. It is separate from the authors’ abstract and is not peer review.

Research summary

The paper posits that age-dependent erosion of RNA regulatory fidelity is a central mechanism driving neuronal vulnerability and neurodegeneration. This is relevant because it identifies a specific molecular pathway (RNA dysregulation) as a potential root cause of aging-related decline, rather than merely describing symptoms or downstream effects like inflammation or proteostasis failure.

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