New Breakthrough in Age-Related Inflammation Could Hold Key to Longer Lifespans
Researchers at Kumamoto University in Japan have made a groundbreaking discovery regarding aging and inflammation. As Japan’s population ages at an accelerated pace, the focus has shifted to increasing healthy lifespans rather than just overall longevity. This new research takes a significant step towards realizing that goal.
The study focuses on “cellular senescence,” a process where cells stop dividing and enter a state associated with chronic inflammation and aging. This phenomenon, known as the senescence-associated secretory phenotype (SASP), involves the secretion of inflammatory proteins that accelerate aging and contribute to diseases like dementia, diabetes, and atherosclerosis.
The ACLY-BRD4 Pathway and Inflammation
Through advanced sequencing and bioinformatics analyses on human fibroblasts, the researchers identified ATP-citrate lyase (ACLY), an enzyme involved in converting citrate to acetyl-CoA, as a key player in activating SASP.
This discovery 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 inflammatory responses in aged mice, suggesting the potential of ACLY inhibitors in managing chronic inflammation and promoting healthier aging.
This exciting breakthrough paves the way for potential new therapies targeting ACLY to combat age-related diseases and improve the quality of life for an aging population.
Reference: “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