A team from Kumamoto University has made a groundbreaking discovery in the field of aging and inflammation. Japan’s aging population is growing at an unprecedented rate, making it crucial to extend healthy life expectancy rather than just life expectancy. The research focuses on “cellular senescence,” a process in which cells stop dividing and enter a state associated with chronic inflammation and aging. This cellular state, known as senescence-associated secretory phenotype (SASP), involves the secretion of inflammatory proteins that accelerate aging and diseases, such as dementia, diabetes, and atherosclerosis.
The researchers discovered that ATP-citrate lyase (ACLY), an enzyme involved in the conversion of citrate to acetyl-CoA, plays a critical role in the activation of SASP. This discovery was made through advanced sequencing and bioinformatics analysis of human fibroblasts, a type of cell found throughout the body. They showed that blocking ACLY activity, either genetically or with inhibitors, significantly reduced the expression of inflammation-related genes in aged cells. This suggests that ACLY is a crucial factor in maintaining the pro-inflammatory environment in aged tissues.
Additionally, the study revealed that ACLY-derived acetyl-CoA modifies histones, proteins that wrap around DNA, 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, highlighting the potential of ACLY inhibitors to control chronic inflammation while maintaining healthy aging.
This discovery opens new avenues for developing treatments that specifically target the damaging aspects of aging cells without eliminating them, offering a promising strategy to control aging and age-related diseases. The research provides a stepping stone toward therapies that can control cellular aging, promoting longer, healthier lives.