A Landmark Discovery by Kumamoto University Scientists
A team of scientists at Kumamoto University has made a landmark discovery in the quest to tackle illnesses tied to aging, such as dementia and atherosclerosis. Published by Neuroscience News, their study shines a light on the enzyme ATP-citrate lyase (ACLY) as a pivotal factor contributing to inflammation within aging cells.
This enzyme is critical to the development of the senescence-associated secretory phenotype (SASP), a condition associated with persistent inflammation and the aging process. Utilizing cutting-edge sequencing and bioinformatics, the Japanese research team pinpointed the significant influence of ACLY in this inflammatory cascade.
Innovative Directions in Treatment Possibilities
The revelation of the essential function of ACLY in activating genes linked to inflammation opens up the door to novel therapeutic approaches. The team demonstrated that by hindering ACLY, there is a notable decline in inflammation gene activation. This reduction of chronic inflammation was observed in elderly mice when the activity of ACLY was impeded, unveiling prospective treatments aimed at mitigating the detrimental effects of aging.
Researcher Nuo Li from the university highlighted that “By hindering the activity of ACLY, either through genetic means or using inhibitors, the activation of genes associated with inflammation in older cells was considerably lessened.” This underscores ACLY’s central role in maintaining an inflammation-prone environment within older tissues, offering an auspicious avenue for handling issues of aging and related diseases.
Moreover, the team discovered the crucial role acetyl-CoA plays in altering histones, which are fundamental to the DNA structure. This process permits the chromatin reader BRD4 to prompt the activation of inflammatory genes. Aiming at the ACLY-BRD4 pathway presents a promising therapeutic target to control SASP-driven chronic inflammation.
As Japan navigates a surge in its elderly population, finding ways to enhance healthy lifespans becomes increasingly pivotal. The findings of this research lay the groundwork for therapeutic strategies to manage cellular senescence, which may contribute to more prolonged and healthier human lives.
A detailed account of this groundbreaking research, titled “Citrate metabolism controls the senescent microenvironment via the remodeling of pro-inflammatory enhancers” by Kan Etoh and colleagues, is featured in Cell Reports. It underscores the effectiveness of targeting ACLY-dependent citrate metabolism for managing SASP and advancing healthy aging. This study provides promising new pathways to enhance life quality in the elderly while addressing the challenges of age-associated health deterioration.
