Dietary Citrate Reverses Vascular Aging and Reduces Atherosclerosis in Mice

This groundbreaking study reveals that citrate, a common food additive and cellular energy source, can significantly reverse age-related vascular dysfunction and extend healthspan in mice. The research addresses a critical gap in longevity science by demonstrating how a simple dietary intervention can combat vascular aging, the primary driver of cardiovascular disease.

Researchers supplemented 18-month-old mice with 1% citrate in drinking water for 6 months and found remarkable improvements across multiple health parameters. Citrate extended both median and maximum lifespan while reducing frailty index scores. Vascular benefits included restored elastic fiber integrity (p<0.05), improved endothelium-dependent relaxation responses to acetylcholine, and reduced expression of aging marker p21. In atherosclerosis-prone ApoE knockout mice fed high-fat diets, citrate reduced atherosclerotic plaque size and necrotic core area.

Physical performance improvements were substantial: citrate increased bone mineral density, maximal grip strength, and balance speed in both aged and atherosclerotic mice. The intervention also elevated HDL cholesterol levels and reduced inflammatory markers like C-reactive protein. Mechanistic studies using human umbilical vein endothelial cells revealed citrate delayed cellular senescence by activating AMPK signaling pathways, improving mitochondrial respiration, ATP production, and reducing reactive oxygen species production.

The clinical implications are significant given citrate's safety profile as an FDA-approved food additive. The study suggests citrate supplementation could offer a practical intervention for age-related cardiovascular diseases, though human trials are needed to confirm these promising preclinical findings.