summary: Researchers have discovered that the enzyme ATP-citrate lyase (ACLY) plays a critical role in stimulating the inflammatory process associated with aging, known as the senescence-associated secretory phenotype (SASP). The study shows that blocking ACLY can reduce the expression of genes associated with inflammation in aging cells, opening the door to potential treatments to combat age-related diseases such as dementia and atherosclerosis.
By inhibiting ACLY, the researchers were able to suppress chronic inflammation in elderly mice, providing a promising new strategy for extending healthy lifespan. This breakthrough could lead to treatments that specifically target the harmful aspects of aging without eliminating aging cells.
Key facts:
- ACLY stimulates inflammation in aging cells by activating inflammatory genes.
- Inhibiting ACLY reduces inflammation-related gene expression in aged mice.
- Targeting the ACLY-BRD4 pathway may promote healthy aging by controlling inflammation.
source: Kumamoto University
A team from Kumamoto University has made a groundbreaking discovery in the field of aging and inflammation. The number of elderly people in Japan is increasing at an unprecedented rate, making it necessary 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 the senescence-associated secretory phenotype (SASP), involves the secretion of inflammatory proteins that accelerate aging and disease, such as dementia, diabetes, and atherosclerosis.
The researchers found that ATP-citrate lyase (ACLY), an enzyme involved in converting citrate to acetyl-CoA, plays a crucial role in activating SASP. The discovery was made using advanced sequencing and bioinformatics analyzes on human fibroblasts, a type of cell found throughout the body.
They demonstrated that blocking ACLY activity, either genetically or using inhibitors, significantly reduced the expression of inflammation-related genes in aging cells. This suggests that ACLY is a critical factor in maintaining the pro-inflammatory environment in old tissue.
Furthermore, the study revealed that acetyl-CoA derived from ACLY modifies histones, the proteins around which DNA is wrapped, allowing the chromatin reader BRD4 to activate inflammatory genes.
By targeting the ACLY-BRD4 pathway, researchers were able to suppress inflammatory responses in aged mice, highlighting the potential of ACLY inhibitors in controlling chronic inflammation while maintaining healthy aging.
This discovery opens new horizons for developing therapies that specifically target the harmful aspects of senescent cells without removing them, providing a promising strategy for managing aging and age-related diseases.
This research provides a starting point toward treatments that can control cell aging and promote longer, healthier lives.
About Inflammation and Aging Research News
author: No me
source: Kumamoto University
communication: No Li – Kumamoto University
image: Image credited to Neuroscience News
Original search: Open access.
“Citrate metabolism controls the aging microenvironment through remodeling of pro-inflammatory promoters“By Kan Itoh et al. Cell reports
a summary
Citrate metabolism controls the aging microenvironment through remodeling of pro-inflammatory promoters
The senescent microenvironment and aged cells themselves contribute to tissue remodeling, chronic inflammation, and age-related dysfunction. However, the metabolic and genomic bases of the senescence-associated secretory phenotype (SASP) remain largely unknown.
Here, we show that ATP-citrate lyase (ACLY), a key enzyme in acetyl coenzyme A (CoA) synthesis, is essential for pro-inflammatory SASP, independent of sustained growth arrest in senescent cells.
Citrate-derived acetyl-CoA facilitates the action of SASP gene enhancers. ACLY based new Enhancers increase recruitment of the chromatin reader BRD4, which causes SASP activation.
Consistently, specific inhibitors of the ACLY-BRD4 axis suppress STAT1-mediated interferon response, creating a pro-inflammatory microenvironment in senescent cells and tissues.
Our results demonstrate that ACLY-dependent citrate metabolism represents a selective target for SASP control designed to promote healthy aging.
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