Hallym University Research Team Led by Jaeyong Lee
Identifies FOXO3a Transcription Factor's Role in Enhancing DNA Repair Activity
Provides Protection Against Radiation Damage and Extends Lifespan
The research team led by Research Professor Jaeyong Lee at the Institute for Cellular Differentiation and Aging, College of Medicine, Hallym University (President Choi Yanghee), has identified that the FOXO3a transcription factor broadly enhances cellular DNA repair activity, providing protective effects against radiation damage and extending lifespan. The results of this study were published in the international journal Biogerontology (SCIE, Impact Factor 4.1, JCR Top 25%).
From the left, Dr. Goezde Inci, Researcher Shende Madhuri Rameshwar, Research Professor Jaeyong Lee. Courtesy of Hallym University
This research was conducted in collaboration with Researcher Shende Madhuri Rameshwar at Hallym University, Professor Kim Sungchan from the Department of Biochemistry, Dr. Goezde Inci, Professor Lim Sunseong from the Department of Food and Nutrition, Park Sangjae, CEO of Medience Co., Ltd., and Kim Byunghak, Director of the Research Institute. The team created genetically modified mice that overexpress the FOXO3a transcription factor upon tetracycline administration, allowing for precise analysis of FOXO3a function.
The results showed that FOXO3a is involved in various physiological activities, including reactive oxygen species elimination, regulation of apoptosis, stem cell activation, and autophagy. The study confirmed that decreased expression of FOXO3a during aging leads to reduced DNA repair activity. By injecting the tetracycline promoter-FOXO3a gene into mouse embryos, the team established genetically modified mice in which FOXO3a is systemically overexpressed upon tetracycline intake.
In particular, using this model, the researchers demonstrated that most DNA repair pathways-including non-homologous end joining, nucleotide excision repair, base excision repair, mismatch repair, and homologous recombination repair-are transcriptionally activated when FOXO3a is overexpressed.
The team evaluated FOXO3a function by exposing these mice to a high dose of 10 Gy gamma radiation. As a result, all wild-type mice that did not overexpress FOXO3a died within 10 days, with destruction of intestinal villi and occurrence of apoptosis. In contrast, mice overexpressing FOXO3a survived for more than 20 days, maintained organ structure, and showed minimal apoptosis. Additionally, FOXO3a-overexpressing mice exhibited an increase of more than 30% in both average and maximum lifespan without side effects, confirming that FOXO3a contributes to enhanced DNA repair activity and lifespan extension.
Research Professor Jaeyong Lee stated, "Based on this study, we have identified new compounds that activate FOXO3a and demonstrated their remarkable therapeutic effects in animal models of dementia and cancer. These compounds have now entered the drug development stage, and we plan to continue research on mechanisms of lifespan extension and therapeutic applications for age-related diseases."
This research was supported by the Basic Science Research Program of the National Research Foundation of Korea and research funding from Medience Co., Ltd.
© The Asia Business Daily(www.asiae.co.kr). All rights reserved.
