50-Your Perfect Grandchild, Radiation Injury, and the Language of Life
They All Involve the Same Biology
When I recovered from large cell lymphoma 31 years ago, I was overcome with gratitude. I had just taken a stroll through the valley of the shadow of death and popped out on the other side. My empathy for those still in the valley was increased many times over. That experience changed me forever. I was much more determined to give back. I have often said that cancer was the worst thing that ever happened to me, and it was the best thing that ever happened to me. My appreciation of family, friends, community, and the simple things of life were enhanced like never before. I was determined to give others the gift that I had received. I was not an oncologist, but the valley is not their exclusive domain. There were plenty of people struggling with heart disease and related conditions. That had been my focus, and I set out to learn more about it.
Now I have come full circle. It looks like I may help some people who are struggling with cancer and treatment complications. I learned that the same core signaling pathways are central to early normal development, wound healing, cardiovascular disease, and related conditions. We have been reviewing that topic through this entire e-book. Two weeks ago, I did not know that my radiation treatments damaged my intestines in a way that is relentlessly progressive, and I began to study to see if the same principles apply to that chronic disease. Once again, these same core mechanisms are central to radiation-induced bowel disease.
This example may be the best demonstration of how these things all tie together. It is another building block in a unified hypothesis of chronic disease and aging. Prior to my serious disease, I had heard about oxidative stress as a driver of cardiovascular disease. I had heard about people taking vitamin E as an antioxidant to live longer and avoid heart disease. I had learned nothing about antioxidants in medical school and it was all very vague to me. I did not understand how it worked and it is a little overwhelming. If you simply enter the search term “oxidative stress” in the National Library of Medicine Database, almost 500,000 scientific journal articles come up. So, a huge amount of research on this topic has been done, it just has not been translated for your benefit. If you narrow the search to “oxidative stress, aging, chronic disease” almost 80,000 articles come up, so there is a very large body of evidence to support the idea that these issues are all linked. There are 5000 articles that address oxidative stress, aging, chronic disease, One of them says, “elevations in plasma markers of oxidative stress in older adults suggest that aging is a state of chronic, systemic oxidative stress, a condition that ensues when the bioavailability of reactive oxygen species (ROS) is increased relative to antioxidant defenses.” Simple translation: when oxidants overcome antioxidant defenses, aging accelerates, and chronic diseases begin.
The specific ways this happens has also been worked out. Look at the upper left corner of the diagram. There are 125,000 journal articles on angiotensin II listed in the National Library of Medicine. Angiotensin II (Ang II) levels increase in the body when addictive food leads to an increase in abdominal fat. Then Ang II engages the AT1 receptor on the cell surface and that leads to increased oxidant production or reactive oxygen species (ROS). That activates the epidermal growth factor receptor (EGFR) which activates the master metabolic switch mTOR and deactivates AMPK. Switching off mTOR and switching on AMPK kills the critical good cells in the organs, causes scar tissue formation, increase inflammation, and ultimately lead to organ failure. It is the same in chronic kidney disease, cirrhosis, heart disease, and emphysema. You see it all around you. Sunlight increases oxidative particle formation in the skin. Farmers who spend a lot of time in the sun have extensive sun damage to their exposed skin. Their necks have extensive wrinkling, and they are more likely to develop skin cancers. If you look at the skin under their T shirts, it is still perfectly smooth.
Here is the craziest part of the story. Every piece of this biology is necessary to normal fetal development. If a mutation interferes with angiotensin II production in the fetus, the kidney does not develop normally. If a pregnant woman takes losartan which blocks angiotensin II, the kidney does not develop properly. To understand this apparent paradox, you must look at this like computer programming language. In the fetus, it is all perfectly coordinated. Genes that produce oxidative particles (ROS) and angiotensin II come into place at just the right time, in just the right place, with the perfect intensity and duration to produce your perfect grandchild. Maternal exposure to drugs, alcohol, cigarettes, and toxins disrupts this perfect symphony with lifelong consequences for the child. If the fetus does not get enough nutrition, that individual has an increases risk of heart disease and diabetes. This same system acts to retain salt and/or water if you are faced with a lack of either. It supports your blood pressure to maintain normal organ function in that setting. The same factors are involved in wound healing. Angiotensin II and oxidative particles play a critical role in normal health, but it is like the Goldilocks story. It must be perfectly balanced. It can’t be too hot, or too cold. It must be just right.
So, when I learned two weeks ago that I was anemic, and it was related to iron loss from radiation bowel disease, I looked to see if the same mechanisms are involved and, sure enough, they are. Radiation activates angiotensin II and that contributes to the scar tissue formation that is blocking my digestive system. The same signaling that leads to a perfect baby and wound healing, kills the functional cells in the bowel and replaces them with scar. Losartan blocks the effect of Ang II and should slow scar formation in radiation-induced bowel disease. It should also protect other organs subjected to radiation. Radiation also increases asymmetric dimethylarginine (ADMA) levels leading to increased ROS production. It activates mTOR. Metformin directly blocks ADMA effects and it inhibits mTOR which sensitizes the cancer to radiation while reducing scarring. Radiation increases the enzyme that makes cholesterol, and statins slow chronic radiation injury. The common denominator is activating mTOR and inactivating AMPK. Exercise, caloric restriction, intermittent fasting, lisinopril, losartan, statins, metformin, aspirin, and empagliflozin all have this effect. This is the reason that optimal medical treatment for cardiovascular and related conditions reduces death from these diseases dramatically. It is also the reason it slows death from all causes and delays the onset of chronic disease.
Genes that are essential to normal fetal development become much less active in early healthy adulthood. These same factors are essential in normal wound healing. Now we know why diverse, seemingly unrelated factors like diet, sedentary life-style, extra abdominal fat, tobacco smoke, stress, toxins, and yes, even radiation activate the same signaling pathways to shorten our lives and cause chronic disease. Optimal medical treatment offers us a way to protect ourselves. If you find this information valuable, and you want to stay up to date on the topic, please subscribe and I welcome your participation in the discussion.