TY - JOUR AU - Willmes, Diana M. AU - Daniels, Martin AU - Kurzbach, Anica AU - Lieske, Stefanie AU - Bechmann, Nicole AU - Schumann, Tina AU - Henke, Christine AU - El-Agroudy, Nermeen N. AU - Da Costa Goncalves, Andrey C. AU - Peitzsch, Mirko AU - Hofmann, Anja AU - Kanczkowski, Waldemar AU - Kräker, Kristin AU - Müller, Dominik N. AU - Morawietz, Henning AU - Deussen, Andreas AU - Wagner, Michael AU - El-Armouche, Ali AU - Helfand, Stephen L. AU - Bornstein, Stephan R. AU - de Cabo, Rafael AU - Bernier, Michel AU - Eisenhofer, Graeme AU - Tank, Jens AU - Jordan, Jens AU - Birkenfeld, Andreas L. T1 - The longevity gene mIndy (I’m Not Dead, Yet) affects blood pressure through sympathoadrenal mechanisms PY - 2021/01/25/ AB - Reduced expression of the plasma membrane citrate transporter INDY (acronym I’m Not Dead, Yet) extends life span in lower organisms. Deletion of the mammalian Indy (mIndy) gene in rodents improves metabolism via mechanisms akin to caloric restriction, known to lower blood pressure (BP) by sympathoadrenal inhibition. We hypothesized that mIndy deletion attenuates sympathoadrenal support of BP. Continuous arterial BP and heart rate (HR) were reduced in mINDY-KO mice. Concomitantly, urinary catecholamine content was lower, and the decreases in BP and HR by mIndy deletion were attenuated after autonomic ganglionic blockade. Catecholamine biosynthesis pathways were reduced in mINDY-KO adrenals using unbiased microarray analysis. Citrate, the main mINDY substrate, increased catecholamine content in pheochromocytoma cells, while pharmacological inhibition of citrate uptake blunted the effect. Our data suggest that deletion of mIndy reduces sympathoadrenal support of BP and HR by attenuating catecholamine biosynthesis. Deletion of mIndy recapitulates beneficial cardiovascular and metabolic responses to caloric restriction, making it an attractive therapeutic target. JF - JCI Insight JA - JCI Insight SN - 2379-3708 DO - 10.1172/jci.insight.136083 VL - 6 IS - 2 UR - https://doi.org/10.1172/jci.insight.136083 PB - The American Society for Clinical Investigation ER -