Longevity & AgingBoosting Cellular NADPH in Blood Vessel Cells Slows Vascular Aging
Researchers used a fluorescent NADPH sensor to reveal that cytosolic NADPH rises in senescent endothelial cells, while mitochondrial NADPH stays unchanged. The rate-limiting enzyme G6PD drives this increase, and its activity is boosted when nitric oxide-mediated inhibition (S-nitrosylation at C385) is reduced. Overexpressing G6PD protected against vascular aging by increasing reduced glutathione and suppressing HDAC3 activity. Screening 1,419 FDA-approved drugs, folic acid emerged as a top candidate; it raises NADPH via MTHFD1 and effectively reversed vascular aging markers in both angiotensin II-infused and naturally aged mice. These findings reframe NADPH metabolism as a causal, targetable driver of vascular aging.
