The longevity gene mIndy (I’m Not Dead, Yet) affects blood pressure through sympathoadrenal mechanisms

Reduced expression of the plasma membrane citrate transporter INDY (acronym I’m Not Dead, Yet) extends life span in lower organisms. Deletion mammalian Indy (mIndy) gene rodents improves metabolism via mechanisms akin to caloric restriction, known blood pressure (BP) by sympathoadrenal inhibition. We hypothesized that mIndy deletion attenuates support BP. Continuous arterial BP and heart rate (HR) were reduced mINDY-KO mice. Concomitantly, urinary catecholamine content was lower, decreases HR attenuated after autonomic ganglionic blockade. Catecholamine biosynthesis pathways adrenals using unbiased microarray analysis. Citrate, main mINDY substrate, increased pheochromocytoma cells, while pharmacological inhibition uptake blunted effect. Our data suggest reduces attenuating biosynthesis. recapitulates beneficial cardiovascular metabolic responses making it an attractive therapeutic target.