PDHA1 Hyperactivation Orchestrates Metabolic Reprogramming Promoting Endothelial Senescence.

Wen-Jing Zhong, Nan-Shi-Yu Yang, Chen-Yu Zhang, Yu-Biao Liu, Ling Jin, An-Jun Ou, Hui Chen, Juan Li, Yong Zhou, Bai-Mei He, Jia-Xi Duan

Department of Geriatric Respiratory and Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China. · pubmed

Paper

Abstract

While recent studies have established links between metabolic reprogramming and inflammatory senescence, the specific metabolic drivers in vascular aging remain incompletely defined. Here, we systematically characterized senescent phenotypes and targeted metabolomic profiles in primary aging endothelial cells, identifying a pyruvate dehydrogenase E1 component subunit alpha (PDHA1)-dependent metabolic shift as a hallmark of cellular senescence. Using a D-galactose-induced senescence model, we demonstrated that endothelial-specific

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Research summary

The paper identifies PDHA1 hyperactivation as a metabolic driver of endothelial senescence in a D-galactose-induced model. This represents an incremental mechanistic insight into vascular aging pathways rather than a breakthrough in lifespan extension or root-cause intervention.

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