Scientists are investigating a potential anti-aging drug that could protect proteasomes and autophagy systems

Aging is an inevitable phenomenon and is accompanied by several comorbidities. This is why research into the effects of aging has become of utmost importance and scientists are looking for ways to slow down aging and its harmful effects on the human body. While aging ultimately leads to the deterioration of all body systems, disruption of protein homeostasis or proteostasis is one of the main reasons behind this.

Our cells have several mechanisms that help detect and degrade damaged or misfolded proteins. These protein quality control systems prevent faulty proteins from aggregating and accumulating, causing cellular stress and long-term problems.

With age, the function of these systems declines, laying the foundation for many age-related degenerative diseases and chronic conditions. Therefore, preventing the disruption of proteostasis mechanisms could be the key to increasing life expectancy and improving the quality of life of older people.

In this sense, a research team from Korea investigated the relationship between two essential protein quality control systems, namely proteasomes and autophagy. The researchers, led by Professor Seogang Hyun from Chung-Ang University in Korea, identified a drug that can maintain the performance of these systems and exhibits interesting anti-aging effects. This study was published online on August 15, 2024 in the journal Autophagy.

Proteasomes are protein complexes that break down faulty proteins into smaller peptides. Autophagy, on the other hand, is a process by which cells degrade and recycle larger structures, including protein aggregates, through the formation of special vesicles. Both systems work together to maintain proteostasis, but the mechanism of their synergistic activation to mitigate the effects of aging is not yet well understood.

Fortunately, an interesting compound finally caught Prof. Hyun's attention. “A few years ago, I learned at a scientific conference that a certain drug called IU1 can increase proteasome activity, which encouraged our group to test its anti-aging effects,” he explains.

The researchers used an animal model to study the aging process: fruit flies of the genus Drosophila. Since fruit flies have a short lifespan and their age-related muscle loss is very similar to that of humans, Drosophila represents a valuable model for studying the aging process. They treated flies with the drug IU1 and measured various behavioral and proteostasis-related parameters.

The results were promising, as Prof. Hyun notes: “Inhibiting the activity of ubiquitin-specific peptidase 14 (USP14), a component of the proteasome complex, with IU1 not only increased proteasome activity but also increased autophagy activity at the same time. We demonstrated that this synergistic mechanism can improve age-related muscle weakness in fruit flies and extend their lifespan.” Notably, similar results were obtained in human cells.

These findings have important implications, particularly with regard to advances in anti-aging therapy. “Reduced protein homeostasis is a major feature of degenerative diseases such as Alzheimer's and Parkinson's. The results of our study could lay the foundation for the development of treatments for various age-related diseases,” says Prof. Hyun.

Provided by Chung Ang University