Kumamoto University makes groundbreaking discovery in aging and inflammation

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 critical to extend healthy lifespans rather than just longevity. 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 the 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 converting citrate into acetyl-CoA, plays a crucial role in activating SASP. This discovery was made using advanced sequencing and bioinformatics analyzes 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 aging cells. This suggests that ACLY is a crucial factor in maintaining the pro-inflammatory environment in aged tissues.

Furthermore, the study revealed that ACLY-derived acetyl-CoA modifies histones, proteins around which DNA wraps, allowing the chromatin reader BRD4 to activate inflammatory genes. By targeting the ACLY-BRD4 pathway, the researchers were able to suppress inflammatory responses in old mice, highlighting the potential of ACLY inhibitors in controlling chronic inflammation while maintaining healthy aging.

This discovery opens new possibilities 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 to therapies that can control cellular aging and promote a longer, healthier life.