Kumamoto University researchers identified ATP-citrate lyase (ACLY) as a key enzyme in driving chronic inflammation in aging cells. Blocking ACLY reduces inflammation-related genes and offers a new strategy for treating aging-related diseases and promoting healthy aging.
A research team at Kumamoto University has made a significant breakthrough in the study of aging and inflammation. With Japan’s population aging at an unprecedented pace, the focus has shifted to extending healthy lifespans, not just overall lifespans.
The research focuses on “cellular senescence,” a process where cells stop dividing and enter a state associated with chronic inflammation and aging. This cellular state, known as the senescence-associated secretory phenotype (SASP), involves the secretion of inflammatory proteins that accelerate aging and disease, such as dementia, diabetes, and atherosclerosis.
The researchers found that ATP-citrate lyase (ACLY), an enzyme involved in converting citrate to acetyl-CoA, plays a critical role in activating SASP. This discovery was made using advanced sequencing and bioinformatics analyses on human fibroblasts, a type of cell found throughout the body.
They demonstrated that blocking ACLY activity, either genetically or with inhibitors, significantly reduced the expression of inflammation-related genes in aging cells. This suggests that ACLY is a crucial factor in maintaining the pro-inflammatory environment in aged tissues.
The ACLY-BRD4 Pathway and Inflammation
Furthermore, the study revealed that ACLY-derived acetyl-CoA modifies histones, proteins that DNA wraps around, allowing the chromatin reader BRD4 to activate inflammatory genes. By targeting the ACLY-BRD4 pathway, the researchers were able to suppress inflammation responses in aged mice, highlighting the potential of ACLY inhibitors in controlling chronic inflammation while maintaining healthy aging.
This discovery opens new avenues for developing treatments that specifically target the harmful aspects of aging cells without removing them, offering a promising strategy for managing aging and age-related diseases. The research provides a stepping stone toward therapies that can control cellular aging, promoting longer, healthier lives.
Reference: “Citrate metabolism controls the senescent microenvironment via the remodeling of pro-inflammatory enhancers” by Kan Etoh, Hirotaka Araki, Tomoaki Koga, Yuko Hino, Kanji Kuribayashi, Shinjiro Hino and Mitsuyoshi Nakao, 22 July 2024, Cell Reports.
DOI: 10.1016/j.celrep.2024.114496
Funding: Japan Society for the Promotion of Science, Coalition of Universities for Research Excellence Program (CURE), Murakami Farm Co., Ltd., Inter-University Research Network for High Depth Omics of Institue of Molecular Embryology and Genetics (IMEG), Kumamoto University
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2 Comments
26/10/24. Nice Research. Thanks to those Scientists and researchers. I have an immediate Problem. About few Millions years ago after the departure of the Dinosaur. The Planet was cool down from the Ice. The heat from the Earth Core and heat from the Sun has turned the Ice into Water. Wright size amount of water. But before that time I have did some Experiment on Mars. How Mars, Earth and some others liveable Planet’s can support Liquid water. From my experiment on Mars and some others planet. I know how much Ice I needed to cool down this Planet. But then there’s a problems. 1. No Planet or Planet’s can naturally supported liquid water. They can only support ICE. Mars did not maintain or Sustains her water for long. Some water on Mars Evaporates by the our Sun while the remaining water on Mars Disappear. I called that LOST WATER. 2. The Weight of the ice toun into Water and the movement of the water up and down will break the planet Apart. So I have that Knowledge and I know how to use that Knowledge to help my self and the Planet. So on Earth Thousands or Millions years ago I made and produce Cables. Am not sure if before or after the departures of the Dinosaur. Anyway I made and produce the cables. I used the cables to Hold the Planet Together as one. The way Humans using Belts to hold there body’s together. And it work’s. The Weight of the water and the water movement up and down did not break the planet Apart. The Planet was hold together for long. When human came along I didn’t say anything because nothing to be said. I worked day and night for years to make the Cables and to be able to Fixed the cables. I fixed the cables round the world only me no body else. Although I had some help from what I called. Anyway about 13 to 15 years ago. I was watching Television when I saw some people or a company from either Spain or French company saw my cables that I used to hold the planet together without any warning they cut my cables. CNN was there to cover the News of the incident. The cables those people cut was inbetween Morroko in Africa and Spain and France. Now before is too late. The same people or the same company that cut the cables should go back and find those cables and joined both sides together. If nobody remember that incident CNN will provide the voltage of the News. Please don’t make me remind you people. As today I can not guarantee how long this Planet will hold together without that cables. Because of the weight of the water and the water movement up and down. So for my sake, for your sake, for the past and for your Future’s sake go and fixed my cables back. I know the water Current will have carried those cables to thousands of kilometres away from were those people cut the cables. I once again used the cables to Hold the Planet Together the way people using their belts to hold themselves together. I will also want CNN to cover the incident. And you have to do this within few Months not years. That is if any of you want to live. If the Planet break into two there will be nothing I can do as that time. So before that will happen fix my cables back. As a Human. If you see what you know its didn’t belongs to human why can’t you let it go? And something that don’t disturb you. They said Curiosity kills the cat. Don’t let’s curiosity kills you. Hun. Thanks. To be continued. M. Luke.
hello can you scientist help problem in DNA.. SCA12+ problem
body imbalance + Brain stroke
kindly help