Reduced Oxidative Stress as a Mechanism for Increased Longevity, Exercise and Heart Failure Protection with Adenylyl Cyclase Type 5 Inhibition

  • Stephen F. VatnerEmail author
  • Jie Zhang
  • Dorothy E. Vatner
Part of the Advances in Biochemistry in Health and Disease book series (ABHD, volume 16)


One common mechanism mediating longevity and healthful aging is the protection against oxidative stress. Most serious diseases that limit aging, in general, and healthful aging, in particular, are linked to increased oxidative stress and increased sympathetic stimulation. Conversely, inhibition of sympathetic tone at any level in the β-adrenergic receptor/adenylyl cyclase/G-protein signaling pathway is a major mechanism protecting against oxidative stress. Disruption of adenylyl cyclase type 5 (AC5), one of the two major isoforms of AC in the heart, protects against oxidative stress resulting in enhanced longevity and more importantly healthful aging as exemplified by increased exercise performance, and protection against diabetes, obesity, cardiomyopathy and cancer, all related to oxidative stress. Despite the overwhelming evidence in animal models that increased oxidative stress is a major mechanism in limiting healthful aging, disappointing clinical trials have impaired the translation to patients. Inhibition of AC5 is a potential novel therapeutic modality, since it extends longevity and protects against diabetes, obesity, cardiomyopathy and cancer, while improving exercise tolerance, with all having an oxidative stress component.


Oxidative stress Human longevity Healthful human aging Cardiomyopathy Sympathetic tone Adenylyl cyclase type 5 


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Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Stephen F. Vatner
    • 1
    Email author
  • Jie Zhang
    • 1
  • Dorothy E. Vatner
    • 1
  1. 1.Department of Cell Biology and Molecular MedicineRutgers, New Jersey Medical SchoolNewarkUSA

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