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DGIST Identifies Mechanism to Recover Aging of Progeria

  • 조회. 832
  • 등록일. 2017.03.30
  • 작성자. Administrator

DGIST Identifies Mechanism to Recover Aging of Progeria






- DGIST’s research teams reveal the mechanism to

recover the function of aging cells in HGPS patients using ROCK inhibitor 



- Propose a new research

direction for studies on the improvement of aging and aging diseases






 



DGIST’s research team has identified a

mechanism that can recover the aging of patients with Hutchinson-Gilford

Progeria Syndrome (HGPS). DGIST announced that the Chair Professor Park SangChul

of New Biology (Head of Well-Aging Research Center) and the research team led

by Professor Lee YoungSam has discovered a drug that can improve the aging of

HGPS patients and identified the mechanism of aging recovery by using the drug.



 



HGPS represents one of premature aging

syndromes. The patients with HGPS experience growth retardation as well as

age-associated symptoms such as skin wrinkles, hair loss, visual impairment,

and cardiovascular diseases. Their average life expectancy is 13 years as they

age 10 times faster than others. When it comes to aging control, improvement of

biological function and solutions for aging of HGPS patients have been big

challenges in academia.








 



This study needs to be highlighted as

the research team has identified the molecular causal relationship between ROCK

protein activation and mitochondrial dysfunction in the progression of cell

senescence for the first time in the world.



 



DGIST’s research team noted that the

level of reactive oxygen species increases when mitochondrial function

diminishes during the progression fibroblasts of the HGPS patients. By

performing high-throughput screening system, the team found ‘Y-27632’ as an

effective agent to control reactive oxygen species and discovered that this

drug is effective in improving mitochondrial function.



 



Mitochondria are intracellular

organelles that play a key role in energy and metabolism in cells. It is known

that mitochondrial dysfunction causes aging of cells as it increases level of

active oxygen and decreases energy production efficiency.



 



The research team found that "Y-27632"

drug inhibits the phosphorylation level of ROCK and increases the oxidative

phosphorylation efficiency of mitochondria. The study also confirms that the

drug recovers mitochondrial function and induces the recovery of aging cells by

reducing nuclear membrane degeneration and genetic damage that are

characteristics of HGPS patient cells. 



 



The Chair Professor Park SangChul stated

“This study is significant as we have newly discovered the means to control

aging. We have also identified the mechanism to recover the function of aging

cell through inhibition and recovery of mitochondrial dysfunction due to

aging.” He added "We will continue to carry out studies that will extend

the healthy lifespan of humans through the verification of the mechanism in

aging animal models as well as progeny animal models.”



 



This study has been published online in

March 19th
 issue of Aging Cell, an international journal of aging

science.
 






Journal Reference



Chemical screening identifies ROCK as a target for recovering mitochondrial function in Hutchinson-Gilford progeria syndrome






Summary



Hutchinson-Gilford progeria syndrome (HGPS) constitutes a genetic disease wherein an aging phenotype manifests in childhood. Recent studies indicate that reactive oxygen species (ROS) play important roles in HGPS phenotype progression. Thus, pharmacological reduction in ROS levels has been proposed as a potentially effective treatment for patient with this disorder. In this study, we performed high-throughput screening to find compounds that could reduce ROS levels in HGPS fibroblasts and identified rho-associated protein kinase (ROCK) inhibitor (Y-27632) as an effective agent. To elucidate the underlying mechanism of ROCK in regulating ROS levels, we performed a yeast two-hybrid screen and discovered that ROCK1 interacts with Rac1b. ROCK activation phosphorylated Rac1b at Ser71 and increased ROS levels by facilitating the interaction between Rac1b and cytochrome c. Conversely, ROCK inactivation with Y-27632 abolished their interaction, concomitant with ROS reduction. Additionally, ROCK activation resulted in mitochondrial dysfunction, whereas ROCK inactivation with Y-27632 induced the recovery of mitochondrial function. Furthermore, a reduction in the frequency of abnormal nuclear morphology and DNA double-strand breaks was observed along with decreased ROS levels. Thus, our study reveals a novel mechanism through which alleviation of the HGPS phenotype is mediated by the recovery of mitochondrial function upon ROCK inactivation.






[DGIST Research News in Media] 










● [The Medical News] Researchers identify mechanism to recover aging of Progeria patients