What did the research discover?
This study explored how amyloid beta (Aβ), a protein linked to Alzheimer’s disease (AD), accelerates the process of protein insolubility that naturally occurs with aging. Protein insolubility happens when proteins clump together and lose their normal function, a hallmark of neurodegenerative diseases like Alzheimer’s, Parkinson’s, and Huntington’s disease.
Using a C. elegans model, researchers found that Aβ expression causes widespread protein insolubility, similar to what happens naturally during aging. They identified a Core Insoluble Proteome (CIP)—a set of proteins that are particularly vulnerable to becoming insoluble under stress conditions. Notably:
- 66% of proteins that become insoluble during normal aging also became insoluble due to Aβ expression, suggesting that Aβ may accelerate age-related protein aggregation.
- Many of these proteins are involved in biological processes linked to chronic age-related diseases (CARDs), including neurodegenerative diseases, cardiovascular disease, metabolic disorders, and cancer.
- The mitochondrial proteins responsible for energy production were particularly affected, leading to disruptions in protein homeostasis and cellular health.
- The gut-derived compound Urolithin A, known to support mitochondrial function, was able to reduce Aβ toxicity, suggesting potential for future treatment strategies.
How can I apply this information?
This study suggests that protein insolubility is not just a feature of Alzheimer’s disease but may be a key factor in many age-related diseases. The findings highlight the importance of mitochondrial health and protein stability in aging and neurodegeneration.
While Urolithin A and other treatments targeting protein homeostasis are still in research stages, this study supports their potential as therapies for Alzheimer’s and other neurodegenerative diseases. Understanding how aging and Aβ contribute to protein aggregation could help develop new strategies to slow or prevent age-related diseases.
Because this is research, more studies are needed to confirm whether targeting protein insolubility can reduce the risk of Alzheimer’s and other age-related diseases in humans. However, the study reinforces the idea that maintaining protein and mitochondrial health may be essential for healthy aging.
Source:
Anderton E, Chamoli M, Bhaumik D, King CD, Xie X, Foulger A, Andersen JK, Schilling B, Lithgow GJ. Amyloid β accelerates age-related proteome-wide protein insolubility. GeroScience. 2024 Oct;46(5):4585-602. https://pubmed.ncbi.nlm.nih.gov/37503138/
