title: Adenylyl cyclase type 5 disruption prolongs longevity and protects the heart against stress.
abstract: Heart failure remains the leading cause of mortality in the USA, despite major advances in therapy over the past several decades, including angiotensin-converting enzyme or angiotensin II inhibitors, vasodilators, calcium-channel blockers and beta-adrenergic receptor blockers. New therapeutic approaches are clearly required and the conceptual origin of these new techniques will be derived from agents that protect the heart against stress and prolong longevity. The combination of stress protection and longevity has been observed in a variety of organisms, from yeast to worms to mammals, and could be the basis for a novel approach to heart failure therapy. A mouse model has been developed with genetic disruption of adenylyl cyclase type 5, which lives one-third longer than the wild-type and is protected from aging-induced, pressure overload-induced and catecholamine-induced stresses. Accordingly, inhibition of this molecule should be considered as a new therapeutic modality for heart failure.
authors.affiliation: Cardiovascular Research Institute, Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry of New Jersey, New Jersey Medical School Newark, NJ 07103, USA. vatnersf@umdnj.edu
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Vatner
authors.forename: Lin
authors.initials: L
authors.lastname: Yan
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ishikawa
authors.forename: Dorothy E
authors.initials: DE
authors.lastname: Vatner
authors.forename: Junichi
authors.initials: J
authors.lastname: Sadoshima
mesh_terms: D000262:Adenylyl Cyclases / Q000235:genetics / Q000502:physiology*; D000818:Animals; D009202:Cardiomyopathies / Q000503:physiopathology; D004195:Disease Models, Animal; D006321:Heart / Q000502:physiology*; D006333:Heart Failure / Q000503:physiopathology; D007527:Isoenzymes / Q000235:genetics / Q000502:physiology*; D008136:Longevity / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D018384:Oxidative Stress / Q000502:physiology*
chemical_list: D007527:Isoenzymes; D000262:Adenylyl Cyclases; C419510:adenylyl cyclase type V