image: Using fruit flies as an animal model, researchers shed light on the synergistic effects of two different mechanisms by which cells destroy faulty proteins that lead to aging. Moreover, by administering a modern drug, IU1, they could prevent age-related decline, leading to longer and healthier lifespans in fruit flies. These findings could be key to developing anti-aging medicine and treatments for challenging diseases that are more common in old age.
Credit: "The Beauty of Old Age" by VinothChandar. Image source: https://openverse.org/image/f0f547af-a803-495f-b55d-bcb2f6e05435?q=old+age
Aging is an inevitable phenomenon and is accompanied by several comorbidities. To this end, research into the effects of aging has become paramount, and scientists are looking for ways to slow down aging and its detrimental impact on the human body. While aging ultimately causes deterioration in all body systems, the disruption of protein homeostasis or ‘proteostasis’ is one of the major underlying reasons.
Our cells have several mechanisms that help detect damaged or misfolded proteins and break them down. These ‘protein quality control’ systems prevent faulty proteins from aggregating and accumulating, causing cellular stress and long-lasting issues. As a person ages, these systems decline in function, which sets the stage for many age-related degenerative diseases and chronic conditions. Thus, preventing the disruption of proteostasis mechanisms could be the key to increasing longevity and improving the quality of life among older adults.
In this vein, a research team from Korea set out to investigate the relationship between two essential protein quality control systems, namely proteasomes and autophagy. The researchers led by Professor Seogang Hyun from Chung-Ang University, Korea, identified a drug that could preserve the performance of these systems, demonstrating interesting anti-aging effects. This study made available online on August 15, 2024 in the journal Autophagy.
Proteasomes are protein complexes that break down faulty proteins into smaller peptides. On the other hand, autophagy is a process by which cells degrade and recycle larger structures, including protein aggregates, through the formation of specialized vesicles. Both systems work in concert to maintain proteostasis, but the mechanism of their synergistic activation to mitigate the effects of aging is not well understood.
Fortunately, an interesting compound ended up catching Prof. Hyun’s attention. “A few years ago, I learned from an academic conference that a certain drug called IU1 can enhance proteasomal activity, which encouraged our group to test its anti-aging effects,” he explains.
The researchers employed an animal model for studying the aging process: fruit flies from the genus Drosophila. Since fruit flies have a short lifespan and their age-related muscle deterioration is quite similar to that in humans, Drosophila constitutes a valuable model for studying aging. They treated flies with the drug IU1 and measured various behavioral- and proteostasis-related parameters. The results were quite promising, as Prof. Hyun remarks: “Inhibiting the activity of ubiquitin specific peptidase 14 (USP14), a component of the proteasome complex, with IU1 enhanced not only proteasome activity but also autophagy activity simultaneously. We demonstrated that this synergistic mechanism could improve age-related muscle weakness in fruit flies and extend their lifespan.” Worth noting that similar results were obtained in human cells.
These findings have important ramifications, especially regarding advances in anti-aging therapy. “Reduced protein homeostasis is a major characteristic of degenerative diseases such as Alzheimer's and Parkinson's disease. The results of our study might lay the groundwork for the development of treatments for various age-related diseases,” highlights Prof. Hyun.
We hope that these newfound insights pave the way for therapeutics that improve quality of life and extend lifespans.
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Reference
DOI: 10.1080/15548627.2024.2389607
Authors: Jin Ju Lima, Sujin Noha, Woojun Kangb, Bom Hyuna, Byung-Hoon Leeb, and Seogang Hyuna
Affiliations
aDepartment of Life Science, Chung-Ang University
bDepartment of New Biology, Daegu-Gyeongbuk Institute of Science & Technology (DGIST)
About Chung-Ang University
Chung-Ang University is a private comprehensive research university located in Seoul, South Korea. It was started as a kindergarten in 1916 and attained university status in 1953. It is fully accredited by the Ministry of Education of Korea. Chung-Ang University conducts research activities under the slogan of “Justice and Truth.” Its new vision for completing 100 years is “The Global Creative Leader.” Chung-Ang University offers undergraduate, postgraduate, and doctoral programs, which encompass a law school, management program, and medical school; it has 16 undergraduate and graduate schools each. Chung-Ang University’s culture and arts programs are considered the best in Korea.
Website: https://neweng.cau.ac.kr/index.do
About Professor Seogang Hyun
Dr. Seogang Hyun is a full Professor at the Department of Life Science of Chung-Ang University. His group has been studying nutritional metabolism, developmental genetics, and aging mechanisms using various model systems, including Drosophila, since 2010. He received his doctoral degree from the Korea Advanced Institute of Science & Technology, Korea. Prof. Hyun has nearly 240 publications to his credit, with an impressive h-index of 20.
Website: https://scholarworks.bwise.kr/cau/researcher-profile?ep=800
Journal
Autophagy
Method of Research
Experimental study
Subject of Research
Animals
Article Title
Pharmacological inhibition of USP14 delays proteostasis-associated aging in a proteasome-dependent but foxo-independent manner
Article Publication Date
15-Aug-2024
COI Statement
No potential conflicts of interest were reported by the author(s).