This is the sixth in a series of posts designed to help you understand how you can extend your healthspan and youthspan. It is part of an effort to help you understand your chronic diseases, what you can do about them, and why it is worth your time. In the last post, I wrote about the way overeating generates oxidants, activates growth factor signaling, and switches on mTOR and switches off AMPK in real time. There is another way that poor diet makes you age and get sick faster.
Abdominal fat makes hormones that increase oxidant production to activate growth factor signaling (the epidermal growth factor receptor) that switches on mTOR and switches off AMPK just like cigarette smoke does. That makes us age faster and get sick sooner.
There are two hormones that are part of the same system. (the renin angiotensin aldosterone system). These hormones (angiotensin II and aldosterone) are proteins made by genes that are essential for fetal development. They are normal and essential genes, but when they are increased by abdominal fat, they cause increases in oxidant production and as with everything else we have discussed, that makes us age and get sick faster.
Research scientists have discovered exactly how these two hormones work. In the fetus they are critical in the formation of the urinary system. In children and healthy young adults, they help us retain water so we survive when we are in a desert and can’t find water. They help maintain the blood pressure if there is injury and blood loss. These genes are important for the survival of young healthy people.
If you eat fast food and processed food, and gain weight as belly fat, these vital, necessary genes make us sick and often kill us. Understanding how they work can help you live a longer healthier life. I have helped you understand that hormones like insulin work like a baseball in a catcher’s mitt. Actually it is more like a key in a lock. The hormone is the key and the catcher’s mitt is a lock. The hormone protein fits precisely into the lock protein and that activates signals like dominoes down stream to increase oxidant production. Angiotensin II activates the AT1receptor which increases oxidant production to activate the EGFR receptor and then mTOR. Aldosterone activates the MR receptor to produce more oxidants and EGFR activation also. EGFR is the funnel through which most upstream signaling occurs. Other growth factors like insulin can be substituted in the growth factor position.
When abdominal fat increases these hormones, it also increases inflammation and so we can explain the link between oxidants, inflammation, aging, chronic diseases and ultimately death. Now here is the best news of all. We have known for a long time that angiotensin II causes high blood pressure. Losartan is a medication that was developed to treat hypertension by fitting into the lock well enough to block angiotensin II access, but not so well that it increased oxidant production and the downstream signaling. Losartan blocks the bad effects of angiotensin II very precisely. It is a precision medicine. That is exactly why it protects every cell and organ in the body more than it lowers the blood pressure. Losartan precisely blocks a root cause of cardiovascular disease and related conditions. Blocking the AT1 receptor decreases oxidant production, EGFR activation, and switching on mTOR to inhibit esophageal cancer growth. Eplerenone blocks the aldosterone receptor in the same way to abort oxidant production, EGFR activation, and downstream mTOR activation. mTOR activation supports scar tissue growth as a part of chronic kidney disease.
This link goes to one of the most important articles that shaped my thinking about chronic diseases and aging. Abdominal fat makes a factor that leads to higher aldosterone levels which makes insulin less effective and causes resistant high blood pressure— high blood pressure that is not controlled on three blood pressure medications. Aldosterone increases oxidant formation and inflammation which leads to insulin resistance, arterial disease, heart disease, and chronic kidney disease. Increased aldosterone levels also lead to decreased insulin production which—together with insulin resistance –are major causes of type 2 diabetes. As you can see in the diagram, aldosterone produces it effects through the MR receptor. Overweight individuals also have higher blood levels of cortisone which also activates the MR receptor. That explains many of the complications with steroid treatments.
The greatest news of all is that we have specific precision treatments that block the MR and AT1 receptors to improve insulin production by the pancreas, reduce resistance to the effects of insulin, and slow the progression of heart and kidney disease. Using losartan and eplerenone are indeed precision treatments that block the root causes of chronic heart disease and related conditions like type 2 diabetes and hypertension. I completely support the idea that lifestyle changes like eating real food, stopping smoking, and getting some exercise are extremely important in your efforts to live a longer healthier life, but make no mistake, medications like metformin, losartan, and eplerenone make a huge difference too. If you don’t use them when appropriate, you are missing the boat. You are missing a chance to increase your healthspan and youthspan.
Eliminating visceral fat early stops these cascades cold and you live longer, and healthier. Yup! Protect your liver, feed your gut!
This is all very interesting. My interpretation is that Dr Bestermann tends to reduce molecules and processes to the status of oxidant/antioxidant, they have no other biochemical purpose.
I'm sure he described losartan and statins as antioxidants in one article. I don't have the biochemistry knowledge as to why you could make some case in that direction, but it comes across as nebulous to me. What he means by this is something else.
Surely everyone could eliminate disease and aging by just taking antioxidants but it hasn't panned out that way at all.
That idea has gone nowhere in reality. I'm not even sure what their role in making you older is. Perhaps Dr Bestermann is saying that they are signalling genes on and off ?
And organisms rely on some level of oxidants and free radicals as well.
However those struggling with diabetes, heart disease and chronic obesity I appreciate may need extra help from different drugs.
I'm not suggesting he's saying this, but I doubt anyone who doesn't need it is missing out on metformin. Metformin for non-diabetics is a kind of self-inflicted injury at best.