Inhibition Of Adenylyl Cyclase Type 5: Healthful Aging Protection


This grant application is in response to a request from the NIA funding opportunity announcement (FOA),which encourages exploratory/developmental research projects to accelerate the pace of development ofnovel therapeutics involving biologics, pharmacological and non-pharmacological approaches forpreventing and treating key health issues affecting the elderly. The current proposal is based on ourlaboratory's development of the adenylyl cyclase type 5 (AC5) knock out (KO) mouse, which is a model forboth longevity and healthful aging. The AC5 KO mouse lives a third longer than its wild type (WT). Moreimportantly for clinical translation, the AC5 KO is protected against diabetes, obesity and cardiac disease andalso improves exercise performance, all major factors required for healthful aging. It is obvious that clinicaltranslation of this mechanism, AC5 inhibition, would be extremely important for the aging population.Accordingly, the goal of this proposal is to compare the effects of two known AC5 inhibitors, Ara Ade and PMC6, on the parameters of healthful aging noted above that are known to be protected in the AC5 KOmouse. Another key clinically relevant feature of these AC5 inhibitors is that they protect ischemic myocardiumand reduce infarct size, even when administered after coronary artery reperfusion. This is key for clinicaltranslation because when patients with myocardial infarction come to the emergency room, the first priority isto reperfuse the occluded coronary artery, leaving no time to administer a drug. Another aim is to develop anew AC5 inhibitor with minimal side effects that can be administered orally.
Effective start/end date8/1/164/30/18


  • National Institutes of Health (NIH)


Knockout Mice
Coronary Vessels
Myocardial Reperfusion
adenylyl cyclase type V
Organized Financing
Biological Products
Hospital Emergency Service
Heart Diseases
Myocardial Infarction
Pharmaceutical Preparations
Adenylyl Cyclase Inhibitors