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A Genetic Change for Achieving a Long and Healthy Life
Researchers identified a single amino acid change in the tumor suppressor protein in PTEN that extends healthy periods while maintaining longevity
Living a long, healthy life is everyone’s wish, but it is not an easy one to achieve. Many aging studies are developing strategies to increase health spans, the period of life spent with good health, without chronic diseases and disabilities. Researchers at KAIST presented new insights for improving the health span by just regulating the activity of a protein.
A research group under Professor Seung-Jae V. Lee from the Department of Biological Sciences identified a single amino acid change in the tumor suppressor protein phosphatase and tensin homolog (PTEN) that dramatically extends healthy periods while maintaining longevity. This study highlights the importance of the well-conserved tumor suppressor protein PTEN in health span regulation, which can be targeted to develop therapies for promoting healthy longevity in humans. The research was published in Nature Communications on September 24, 2021.
Insulin and insulin-like growth factor-1 (IGF-1) signaling (IIS) is one of the evolutionarily conserved aging-modulatory pathways present in life forms ranging from tiny roundworms to humans. The proper reduction of IIS leads to longevity in animals but often causes defects in multiple health parameters including impaired motility, reproduction, and growth.
The research team found that a specific amino acid change in the PTEN protein improves health status while retaining the longevity conferred by reduced IIS. They used the roundworm C. elegans, an excellent model animal that has been widely used for aging research, mainly because of its very short normal lifespan of about two to three weeks. The PTEN protein is a phosphatase that removes phosphate from lipids as well as proteins. Interestingly, the newly identified amino acid change delicately recalibrated the IIS by partially maintaining protein phosphatase activity while reducing lipid phosphatase activity.
As a result, the amino acid change in the PTEN protein maintained the activity of the longevity-promoting transcription factor Forkhead Box O (FOXO) protein while restricting the detrimental upregulation of another transcription factor, NRF2, leading to long and healthy life in animals with reduced IIS.
Professor Lee said, “Our study raises the exciting possibility of simultaneously promoting longevity and health in humans by slightly tweaking the activity of one protein, PTEN.”
This work was supported by the MInistry of Science and ICT through the National Research Foundation of Korea.
-Publication:Hae-Eun H. Park, Wooseon Hwang, Seokjin Ham, Eunah Kim, Ozlem Altintas, Sangsoon Park, Heehwa G. Son, Yujin Lee, Dongyeop Lee, Won Do Heo, and Seung-Jae V. Lee. 2021. “A PTEN variant uncouples longevity from impaired fitness in Caenorhabditis elegans with reduced insulin/IGF-1 signaling,” Nature Communications, 12(1), 5631. (https://doi.org/10.1038/s41467-021-25920-w)
-ProfileProfessor Seung-Jae V. LeeMolecular Genetics of Aging LaboratoryDepartment of Biological Sciences KAIST
2021.11.19 View 6883 -
KAISTian of the Year 2016: Professor Hee-Sung Park
Professor Hee-Sung Park of the Department of Chemistry has been named the KAISTian of 2016. President Sung-Mo Kang awarded him at the New Year ceremony on January 2, 2017.
The KAISTian of the Year recognizes the most outstanding professor whose research and scholarship made significant achievements for the year. The Selection Committee announced that Professor Park was chosen as the 16th awardee in recognition of his developing new methods to incorporate unnatural amino acids into proteins.
Earning his Ph.D. in chemical engineering at KAIST in 2000, Professor Park has been a professor at KAIST since 2009. His research focuses on the production of synthetic proteins and the generation of diverse protein functions as well as the designing and engineering of new translation machinery for genetic code expansion, and the application of synthetic biology techniques for basic cell biology and applied medical science.
He developed a tool to engineer designer proteins via diverse chemical modifications, providing a novel platform for investigating numerous diseases such as cancer and dementia. Post-translational modifications (PTMs) are constantly taking place during or after protein biosynthesis. PTMs play a vital role in expanding protein functional diversity and, as a result, critically affect numerous biological processes. Abnormal PTMs have been known to trigger various diseases including cancer and dementia. Therefore, this technology, that enables proteins to reproduce with specific modifications at selected residues, will significantly help establish experimental strategies to investigate fundamental biological mechanisms including the development of targeted cancer therapies.
Professor Park’s research results appeared in the September 28, 2016 edition of Science. For more on Professor Park's research, please visit:
http://kaistcompass.kaist.ac.kr/?issues=fall-2016&magazine=a-chemical-biology-route-to-site-specific-authentic-protein-modifications
http://science.sciencemag.org/content/early/2016/09/28/science.aah4428
http://www.kaist.ac.kr/html/en/news/podcast.html (Podcast: Season 6 Episode 7: When good proteins go bad )
2017.01.10 View 7373 -
Maximum Yield Amino Acid-Producing Microorganism Developed with use of System Biotechnology
Maximum Yield Amino Acid-Producing Microorganism Developed with use of System Biotechnology
A team led by Sang-Yup Lee, a distinguished professor of Chemical and Biomolecular Engineering and chair professor of LG Chemical, has succeeded in developing maximum yield L-valine-producing microorganism by using System Biotechnology methods. The research results will be published at the April fourth week (April 23 - 27) edition of the Proceedings of the National Academy of Sciences (PNAS) of the USA.
Prof. Lee’s team has developed maximum yield amino acid-producing microorganism (target substance of L-valine, an essential amino-acid) by using microorganism E cell system and simulation methods.
His team produced initial producing microorganism by selectively operating necessary parts in colon bacillus genome and excavated preliminary target gene which is to newly be operated through transcriptome analysis using DNA chips. Then they performed a great amount of gene deletion experiment on computer by using MBEL979, E-cells of colon bacillus, and excavated secondary engineering targets. And they finally succeeded in developing maximum yield valine-producing microorganism that can extract 37.8 grams of valine from 100 grams of glucose by applying experiment results to the actual development of microorganism so as to achieve the optimization of metabolic flux in cells,
Prof. Lee said, “Since successfully used for the development of microorganism on a systematic system level, system biotechnology methods are expected to significantly contribute to the development of all biotechnology-relevant industries. At the beginning, we had huge obstacles in fusing IT and BT, but my team mates cleverly overcame such obstacles, hence I’m very proud of them.” The producing microorganism and its developing methods are pending international applications (PCT).
2007.04.26 View 13577