Guest: Dr. Gabriel Bever, Ph.D. - Dr. Qinchuan Wang, PH.D. - Linda Brent Ph.D.
Antagonistic pleiotropy is a foundational theory that predicts aging-related diseases are the result of evolved genetic traits conferring advantages early in life. Here we examine CaMKII, a pluripotent signaling molecule that contributes to common aging-related diseases, and find that its activation by reactive oxygen species (ROS) was acquired more than half-a-billion years ago along the vertebrate stem lineage. Functional experiments using genetically engineered mice and flies reveal ancestral vertebrates were poised to benefit from the union of ROS and CaMKII, which conferred physiological advantage by allowing ROS to increase intracellular Ca 2+and activate transcriptional programs important for exercise and Immunity. Enhanced sensitivity to the adverse effects of ROS in diseases and aging is thus a trade-off for positive traits that facilitated the early and continued evolutionary success of vertebrates.
PLUS
The practice of castration and ovariectomization is commonplace among veterinarians today. Dogs are spayed and neutered at very young ages removing all sex hormones which have important roles in the health and immune systems of dogs. We look at castrated male dogs who received testosterone replacement after being neutered to identify is any health advantages were conferred.
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Show Notes:
Muscle Protein That Makes Vertebrates Fit Linked to Limiting Lifespan + HRT For Dogs Improves Health
[4:25] Inspiration for this study.
- The concept of senescence.
- Statistically speaking, if senescence stopped after your 18th birthday, you would have a 50% chance of living to 700.
[8:00] Activation of kinase lead to inflammatory programs.
- Transient inflammation is important, but chronic inflammation takes a toll on the body.
[12:25] Antagonistic pleiotropy.
- A single gene may have more than one trait, providing a positive effect early in life but showing negative effects later in life.
[16:15] What about the buildup of bio debris?
[19:30] Do neo-natal genes play a role?
[23:45] CaMK2
- Can be activated by reactive oxygen species.
- Its oxidation can be involved in heart attacks, cancer, and atrial fibrillation.
- Why would nature keep it then?
- There must be a positive effect as well.
- Qinchuan found that it has endurance and output benefits.
- Does not exist in invertebrates.
[38:59] Hormesis
[42:56] If one is going to use antioxidants, when should they be used?
[1:00:05] What should clinicians and laypeople take from this study?
- An evolutionary Lense is a valuable tool.
[1:08:08] Neutered dogs should have a replacement hormone protocol.
[1:13:07] The veterinary field is relatively slow to change.
[1:15:03] The purpose of neutering a dog.
[1:20:53] How this ties into cancer in dogs.
[1:25:45] Neutered dogs are more aggressive than non-neutered dogs.
[1:28:20] The pharmakinetics of testosterone injections.
