AGGF1, an endothelial protein that declines with age, regulates blood pressure through a signaling pathway that controls mitochondrial function and nitric oxide production. Loss of AGGF1 accelerates vascular aging and elevates blood pressure in male mice, while restoring AGGF1 expression reverses these changes, identifying a potential intervention target for age-related hypertension.
Key Points
- AGGF1 expression declines with age and correlates inversely with blood pressure
- AGGF1 loss triggers mitochondrial dysfunction and reduces protective eNOS signaling
- AGGF1 restoration reverses vascular aging and suppresses age-elevated blood pressure
Longevity Analysis
This research identifies a specific molecular mechanism linking age-related decline in endothelial function to hypertension—one of the most prevalent drivers of cardiovascular mortality. The AGGF1/SESN2/p-eNOS axis represents a pathway where mitochondrial health directly governs vascular tone regulation. Rather than treating elevated blood pressure as an inevitable consequence of aging, this work suggests the decline is reversible through restoration of a single regulatory protein, shifting the therapeutic frame from symptom management to restoration of age-suppressed signaling. Understanding how mitochondrial dysfunction in endothelial cells translates to systemic pressure elevation also clarifies why interventions that improve cellular energy production and reduce oxidative stress show cardiovascular benefits across multiple populations.
Original published by Wiley Aging Cell, by Weixin Lv, Xiaojuan Zhong, Qiang Yuan, Xueting Gong, Ya Zhao, Shilin Zhang, Andong Wu, Ming Wan, Xueer Li, Yangyi Zheng, Jiankun Liu, Bingbing Zhou, Yuanzheng Zhu, Limin Zhao, Qiquan Wang, Yang Xiang, Xiao‐Li Tian .