Eternygen GmbH Press release
Berlin, January 27, 2021
The longevity gene mINDY (I’m Not Dead, Yet) not only prevents metabolic disease, but also lowers arterial blood pressure and heart rate
Berlin, Germany, January 27, 2021 – Eternygen announces today the publication of Prof. Dr. Andreas Birkenfeld, one of Eternygen’s scientific founders in Journal of Clinical Investigation (JCI) Insight. He presented data showing that the longevity gene mammalian Indy (mINDY) is involved in blood pressure regulation. Reduced expression of mINDY which is known to extend life span in lower organisms and to prevent from diet induced obesity, fatty liver and insulin resistance in mice, has now been shown to lower blood pressure and heart rate in rodents. The authors provided mechanistic insights for the underlying physiological mechanism based on in vivo data in a genetic knock out model as well as microarray and in vitro studies. Furthermore, the hypothesis is supported by confirming critical effects in vitro using a small molecule inhibitor of mINDY. The authors conclude that deletion of mIndy recapitulates beneficial cardiovascular and metabolic responses to caloric restriction, making it an attractive therapeutic target.
Andreas Birkenfeld and colleagues provide a comprehensive study showing that mIndy deletion attenuates sympathoadrenal support of blood pressure and reduced arterial blood pressure and heart rate in a murine knockout model. Blood pressure was assessed invasively using intra-arterial pressure probes over several days. Urinary analysis for catecholamines and metanephrines as well as unbiased transcriptomic analysis of adrenal glands identified the affected biosynthetic pathways. Indeed, catecholamine biosynthesis was attenuated in mINDY-KO adrenals, whereas plasma steroids and steroid hormone synthesis were unaffected.
In vitro studies on an adrenal cell line supported this hypothesis. mIndy codes for a carboxylic acid transporter protein expressed in plasma membrane. Citrate, the main substrate of the mINDY transporter, increased catecholamine content, while pharmacological inhibition of mINDY by a small molecule inhibitor blunted the effect.
The study provided further insights into the physiological mechanisms of the beneficial effects of reducing mINDY activity which is known to protect from diet and aging induced metabolic diseases by mechanisms akin to caloric restriction. Therefore, the data showed a novel mechanism contributing to cardiometabolic cross talk and further supporting mINDY as a promising target for the whole spectrum of metabolic syndrome components, including increased blood pressure.
The study was published from the Institute of Diabetes Research and Metabolic Disorders (IDM) of the Helmholtz Center Munich at the University Tübingen and the Clinic of Diabetes, Endocrinology and Nephrology of the University Hospital Tübingen.
Willmes DM, Daniels MA, Kurzbach A, Lieske S, Bechmann N, Schumann T, Henke C, El-Agroudy N, Da Costa Goncalves AC, Peitzsch M, Hofmann A, Kanczkowski W, Kräker K, Müller DN, Morawietz H, Deussen A, Wagner M, El-Armouche A, Helfand SL, Bornstein SR, de Cabo R, Bernier M, Eisenhofer G, Tank J, Jordan J, Birkenfeld AL. The longevity gene mIndy (I’m Not Dead, Yet) affects blood pressure through sympathoadrenal mechanisms. JCI Insight. 2021, doi.org/ 10.1172/jci.insight.136083
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Eternygen is a Berlin-based Biotech Company founded in June 2012 to focus on the research, development and marketing of NaCT inhibitors for the treatment of dietary-related metabolic diseases. The founding team consists of renowned scientists from leading German universities and academic institutes as well as serial entrepreneurs from the venture and industry community. Eternygen is a virtual company supported by a network of senior industry experts and contract research organizations. Eternygen shareholders include Epidarex Capital, Evotec SE, VC Fonds Technologie, Berlin, Germany managed by IBB Venture, and two renowned family offices. For additional information please go to www.eternygen.com
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