DHCR24, an endoplasmic reticulum enzyme, protects vascular endothelial cells from DNA damage and senescence by regulating calcium signaling through the ENKUR pathway. Loss of DHCR24 triggers calcium overload, mitochondrial dysfunction, and accelerated aging in blood vessel cells—a mechanism potentially reversible through DHCR24 restoration or calcium pathway modulation.
Key Points
- DHCR24 deficiency causes calcium overload via ENKUR upregulation
- Calcium dysregulation drives ER stress and mitochondrial dysfunction
- DHCR24 restoration suppresses DNA damage response in aging cells
Longevity Analysis
Vascular endothelial health is foundational to circulation and oxygen delivery throughout aging. This research identifies a specific molecular brake on endothelial senescence: when DHCR24 activity declines with age, calcium signaling spirals out of control, triggering the cascade of cellular dysfunction that characterizes vascular aging. The therapeutic implication is direct—restoring DHCR24 function or interrupting the ENKUR-calcium pathway offers a tractable intervention point to slow vascular aging and the cardiovascular decline associated with aging. This mechanism also highlights how a single enzyme coordinates multiple stress responses (ER homeostasis, mitochondrial function, DNA integrity), revealing that age-related diseases may be addressable at their convergence points rather than through single-target approaches.
Original published by Wiley Aging Cell, by Han Li, Zhen Yang, Wukaiyang Liang, Jie Huang, Tianyi Ji, Hao Nie, Zixin Wan, Yuqi Qiu, Yi Huang, Le Zhang, Cuntai Zhang, Jinhua Yan .