RNA-binding proteins in aging and age-related diseases: roles, mechanisms, and a large language model analysis

Clinical Snapshot

Key Findings

• P Value: Not reported

• Effect Size: Not applicable — no quantitative effect sizes reported; findings are mechanistic and associative

• Primary Outcome: Narrative synthesis of molecular mechanisms by which six RBPs (HuR, AUF1, TTP, IGF2BP2, QKI, LARP7) regulate post-transcriptional gene expression in the context of aging and age-related diseases, including cardiovascular disease, neurodegeneration, cancer, and metabolic disorders

• Nnt Or Sensitivity: Not applicable — no therapeutic, diagnostic, or prognostic metrics calculated; the text-mining analysis does not report sensitivity, specificity, or predictive values for RBP-disease associations

• Confidence Interval: Not reported

Clinical Application

No clinical interventions are proposed or evaluated. RBP-targeted therapies are not currently in routine clinical use. The mechanistic framework described could inform future drug discovery programmes targeting RBP–RNA interactions, but significant translational work — including preclinical validation and clinical trials — would be required before any clinical implementation. No RBP-targeted therapies are currently listed on the Australian Pharmaceutical Benefits Scheme (PBS) or approved by the Therapeutic Goods Administration (TGA) for aging-related indications. The RACGP does not currently reference RBP biology in clinical guidelines for age-related disease management. The review's findings are relevant to Australian researchers in the National Health and Medical Research Council (NHMRC) funding landscape, particularly programs addressing healthy aging, dementia (consistent with the National Dementia Action Plan), and metabolic disease. Australian geriatric medicine and molecular biology communities may find the mechanistic framework useful for hypothesis generation. No immediate PBS or prescribing implications exist. Broadly applicable to research contexts involving older adults with age-related diseases. Direct clinical application is premature; findings are most relevant to researchers in molecular gerontology, drug target identification, and biomarker discovery. Potential future relevance to patients with neurodegenerative diseases, cardiovascular disease, type 2 diabetes, sarcopenia, and age-related cancers.

Abstract

Aging is a progressive and irreversible biological process that contributes to the pathogenesis of numerous age-related diseases. Elucidating the molecular mechanisms of aging is crucial for promoting healthy aging and extending healthspan. RNA-binding proteins (RBPs) are pivotal regulators of post-transcriptional gene expression and play essential roles in diverse biological processes. RBPs interact with both coding and non-coding RNAs to regulate RNA metabolism, stability, localization, and translation. Dysregulated RBP-RNA interactions have been closely associated with aging and age-related diseases. This review systematically summarizes the structural characteristics of RBPs and the evolution of methods used to study them. We focus on the molecular mechanisms of six key RBPs, namely HuR, AUF1, TTP, IGF2BP2, QKI, and LARP7, in the context of aging and age-related diseases. In addition, we discuss the regulatory functions of post-translational modifications of RBPs. Furthermore, we provide a multidimensional overview of RBP involvement in aging and age-related diseases through large language model (LLM)-based text-mining analysis. Our study provides a foundation for the comprehensive characterization of RBPs in aging and age-related diseases.

References

1. 1.Han, Q., Huang, S., Luo, S., & Yang, D. (2026). RNA-binding proteins in aging and age-related diseases: roles, mechanisms, and a large language model analysis. Biogerontology. https://doi.org/10.1080/07853890.2024.2443046