Age is the Greatest Risk Factor for Chronic Disease Development and Death

Several readers have said that diet and exercise are all that you need to live the longest healthiest life that is possible. They are ignoring one important fact. Age is the greatest risk factor for death and chronic illnesses like heart artery disease. Diet and exercise can slow aging and delay chronic disease to a degree, but to receive maximal benefit, you must use certain medications to interfere with the genetic regulation (epigenetics), increased oxidant production, and resulting inflammation that contribute to more rapid aging and chronic illness development.

Epigenetics is a key factor in chronic diseases and aging. This video from NOVA is a great introduction to epigenetics.  It is very interesting to study identical twins in this regard. The DNA or computer code in identical twins is exactly the same at birth, but genetic expression becomes very different as twins age. Age is also one of the most powerful risk factors for heart artery disease. It does not matter how stringent your diet or how much you exercise, sooner or later aging itself will lead to artery disease or cancer and that will kill you. “In both sexes, the risk of CHD (heart artery disease) increased markedly with age. In most populations, serum total cholesterol increases as age increases. In men, this increase usually levels off around the age of 45 to 50 years, whereas in women, the increase continues sharply until the age of 60 to 65 years. High blood pressure also increases with age even if you have a heart healthy lifestyle. Age is one of the most important risk factors for the development of prediabetes and diabetes. It does not matter how stringent the diet or how much we exercise, ultimately we age, get sick and die. The ultimate question? How can we slow that down? How can we be fully functional, independent, and living a normal life longer? Diet and exercise are important, but they are not the whole story.

Oxidant production increases as we age while antioxidant protection is simultaneously declining. That imbalance is called oxidative stress and that is a central factor in chronic disease development and aging itself. This extensive review of the topic is worth your time. The oxidative stress theory of aging is based on this idea.

One factor in this imbalance has not received nearly enough attention. Asymmetric dimethylarginine (ADMA) was the topic of enthusiastic study by leading scientists at Stanford two decades ago. It was described as an uber marker, a common denominator in all cardiovascular disease that explained many heart attacks not related to other risk factors. ADMA has a very important effect that attracted all the attention. It shifts production of nitric oxide, a major factor in maintaining arterial health, to an oxidative particle that damages arteries, causes breaks in DNA strands, and changes proteins so that they no longer function. The investigators were right. ADMA and the increased oxidant production that comes from increased ADMA is a major factor in chronic illness and aging. ADMA blood levels are indeed a strong predictor of all-cause mortality in the elderly. The enthusiasm died out because the investigators could not find a treatment that made a difference. That is because they were focused on the wrong part of the ADMA story.

ADMA is an amino acid that is formed as a byproduct of gene activation. In the fetus and child, gene activation is perfectly coordinated.  A fetus lacking the enzyme that makes most ADMA only survives a few days. ADMA levels correlate with normal growth in children but then they fall in healthy young adults. In adults, blood ADMA levels increase with age with an approximately two-fold increase in elderly people and higher ADMA levels correlate powerfully with all cause mortality. Increased ADMA levels lead to oxidative stress and oxidative stress increases ADMA levels in a vicious cycle. ADMA levels are a marker for epigenetic activity. The higher the ADMA level, the more epigenetic change and gene activation is going on in the body.

That all leads to the medical importance of ADMA and the fact that we can precisely block ADMA effects. As you can see in the diagram above, metformin and ADMA are so structurally similar on the left side in the diagram above that metformin blocks the effect of ADMA like a laser. That explains why metformin reduces heart attacks by nearly 40% in diabetes compared with other approaches that achieve the same blood sugar level. It explains why simply getting the sugar down is not enough and you cannot reverse type 2 diabetes. It helps you understand that metformin is an antioxidant that works. Lisinopril or losartan and spironolactone or eplerenone  for hypertension and statins for cholesterol are also antioxidants that work to reduce death and diabetic complications more than they lower the target risk factor as you can see from the diagram below. They are antioxidants that work! You can easily see how this all ties together in the diagram below.

Our healthcare system is focused on rescue late in disease processes. That is like communicating with smoke signals. The new science of medicine is so powerful that we understand the mechanisms of chronic disease and aging enough to prolong healthier life by 8 years even in older, sick people. Prolonging healthier life in human can be a reality now. It does not need to be that hard. Getting some exercise is very important. Eating whole, real food is critical. They reduce mTOR signaling and amplify AMPK. The medicines in the green boxes do exactly the same thing. If we shift out system to support a longer, healthier life, we will spend less on health care. The very best care is the least expensive care. That is what this site is all about!