A groundbreaking discovery has been made by a team at Kumamoto University in the field of aging and inflammation, shedding light on new possibilities for extending healthy lifespans amidst Japan’s rapidly aging population. The research focuses on the process of “cellular senescence,” where cells cease dividing and enter a state associated with chronic inflammation and aging. This cellular state, known as the senescence-associated secretory phenotype (SASP), is characterized by the secretion of inflammatory proteins that accelerate the aging process and contribute to various age-related diseases such as dementia, diabetes, and atherosclerosis.
Through advanced sequencing and bioinformatics analyses on human fibroblasts, the researchers discovered the crucial role of ATP-citrate lyase (ACLY) in activating SASP. ACLY is an enzyme that plays a key role in converting citrate to acetyl-CoA. By blocking ACLY activity, either genetically or through the use of inhibitors, the expression of inflammation-related genes in aging cells was significantly reduced. This finding suggests that ACLY is essential for maintaining the pro-inflammatory environment in aged tissues.
Moreover, the study unveiled that ACLY-derived acetyl-CoA modifies histones, proteins around which DNA wraps, enabling 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, demonstrating the potential of ACLY inhibitors in controlling chronic inflammation while promoting healthy aging.
This groundbreaking discovery paves the way for the development of treatments that specifically target the harmful aspects of aging cells without eliminating them, presenting a promising strategy for managing aging and age-related diseases. This research represents a significant step towards therapies that can regulate cellular aging, ultimately fostering longer and healthier lives.
