A research team at Kumamoto University has made a significant advancement in understanding aging and inflammation. With Japan’s elderly population increasing rapidly, it is essential to focus on extending the duration of healthy living instead of merely increasing the number of years lived. The study examines a phenomenon referred to as “cellular senescence,” where cells cease to divide and enter a stage linked to ongoing inflammation and aging. This particular condition is identified as the senescence-associated secretory phenotype (SASP), which entails the release of inflammatory proteins that contribute to accelerated aging and various diseases, including dementia, diabetes, and atherosclerosis.
The research team discovered that an enzyme called ATP-citrate lyase (ACLY), which plays a vital role in converting citrate into acetyl-CoA, is key to initiating SASP. This finding emerged from cutting-edge sequencing and bioinformatics analyses conducted on human fibroblasts, a common type of cell in the body. They showed that inhibiting ACLY’s function, either through genetic alterations or using specific inhibitors, significantly lowered the expression of genes related to inflammation in aging cells. This indicates that ACLY is essential for sustaining the pro-inflammatory environment found in aged tissues.
Additionally, the study uncovered that acetyl-CoA derived from ACLY modifies histones, which are proteins that DNA coils around. This modification enables the chromatin reader BRD4 to activate inflammatory genes. By targeting the ACLY-BRD4 pathway, the researchers successfully reduced inflammation responses in older mice, demonstrating the promising potential of ACLY inhibitors in managing chronic inflammation while supporting healthy aging.
This breakthrough paves the way for new treatment options that specifically address the detrimental aspects of aging cells without eliminating them, offering a hopeful approach to tackling aging and age-related conditions. The research serves as a foundation for developing therapies aimed at controlling cellular aging, ultimately fostering longer and healthier lifespans.
