A Unifying Hypothesis of Chronic Disease and Aging

By William H. Bestermann, Jr., MD | Published 10/31/2018 1

chronic disease-aging two senior women hiking

You can extend your healthy lifespan if you maintain your body like you would your favorite car. (Photo source: iStock)

Look around. You can see differences in the rate of aging everywhere. Some 50-year-old people look 80 and some 80-year-old people look 50. It’s just the way they look. The 80-year-old people who look 50 are more active, have fewer chronic diseases. Their biological age in terms of cellular function is younger than their actual age in years. A compelling body of emerging scientific evidence can finally help us understand how this works. It can also help us develop a unifying hypothesis of chronic disease and aging.

You don’t have to age or die prematurely. And, you don’t have to develop chronic disease early. Most importantly, you can extend your healthy lifespan in ways that allow you to continue to contribute and function in the way that you want to. And, by the way, you don’t have to eat sticks and grass to do it!

But there are a few things that you must do. First of all, you should maintain your body just like you maintain your car.

What we can learn from aging skin

Let’s get started by talking about something that you can see for yourself: your skin. Your skin is an organ where you can readily see the effects of aging. Unlike the skin of children that is smooth and tumor-free, older skin is wrinkled and is likely to be diseased with benign and malignant growths.

Sunbathing without skin protection and cigarette smoking combine to accelerate skin aging. Exposure to them can cause a 50-year-old person to have skin like an 80-year-old. Other environmental factors like poor diet and pollution may also come into play. It is important to note that in some people, skin age and overall health age may be out of sync. 

Reactive oxygen species

New science provides compelling evidence of why this occurs at the level of molecular biology. Accelerated aging and disease in the skin are largely driven by excess oxidative particles.

These particles are generated by sun exposure and other environmental factors. These reactive oxygen species (ROS) in turn activate signaling pathways that degrade the elastic fibers and other components that create a youthful skin appearance and texture.

These same signaling pathways account for the relationship between accelerated skin aging and benign or malignant growths on the skin. Cigarette smoke contains 1015 oxidative particles per puff. Adding more oxidative particles from cigarette smoke accelerates skin aging and increases the likelihood of skin cancer.

Related content: Antioxidants and Free Radicals: Hope or Hype

Epigenetics and skin aging

The same genes that are related to accelerated skin aging, skin cancer, and chronic skin diseases like psoriasis, are also required for normal skin development. Those same genes are activated at just the right time, in just the right place, for just the right duration in the fetus to develop normal skin.

They become much less active in the 20-year-old with perfectly normal skin. Then environmental factors, like sun exposure and cigarette smoking, later in life reactivate those genes and contribute to accelerated aging, skin cancer, and benign growths.

This information is not a matter of belief. We all know people who love to smoke and lay out in the sun. You can see with your own eyes that they look older.

The good news is this. The mechanisms that cause these changes are becoming clear and you can reduce your risk of chronic disease and slow aging with a few simple measures that are easy to understand.

It’s not just about aging skin

You can see these changes in the skin but that is not the main story. The changes are not limited to the skin, the acceleration of aging occurs in every cell in the body.

Normal genes and oxidative particle signaling are critical to normal fetal development and growth. However, when growth and development are complete in the normal 20-year old, those genes become much less active.

Later in life, aging, overeating, abdominal obesity, and cigarette smoke reactivate those genes to accelerate aging and increase the incidence of premature chronic disease.

The impact of processed food

Some foods can also be an important source of oxidative particles. Over thousands of years, humans have eaten real whole foods. But that changed with the ubiquitous availability of highly processed foods that are cheap and long-lasting. 

Now, many Americans today eat products from big food companies that are a combination of sugar, processed carbohydrates, fat, salt, flavorings, and preservatives.

In addition, we find that people often eat these artificial foods even when they are not hungry.  Further, the more they eat, the more they want.

These foods are literally addictive. As with any addictive substance, it is very difficult to cut down on consumption. The problem is compounded because processed carbs turn to sugar very quickly.

The body converts food to energy via oxidation that occurs in the mitochondria, but this is not a perfect process. Some oxidative particles always leak out, even with healthy food. 

Think of these leaks like a hose with the excess sugar leading to increased pressure in the hose. That excess pressure increases the leaks dramatically. This leads to the production of  many more oxidative particles that contribute further to accelerated aging and chronic disease.

To make it worse, processed foods lose most of the beneficial antioxidants that are embedded in natural whole foods during the milling process. Eating fast food and processed food regularly has the same type of impact as smoking and exposes the body to large numbers of damaging oxidative particles.


Aging itself contributes to the problem because antioxidant defenses deteriorate with time. Aging, cigarette smoke, and too much food create a vicious cycle of increased oxidative stress, increased cell damage, chronic disease, and accelerated aging.

Related Content:  mTOR and the Science of Aging and Chronic Disease

Chronic disease

Addictive food leads to increased abdominal fat accumulation which activates genes that produce still more oxidative particles while increasing the blood pressure, cholesterol, and glucose. These factors damage the body further still.

Graphic of relationship oxidative stress to chronic illness 650 x 443)

Source: Clinical Interventions in Aging (2018 13:757-772) (Open access article)

Taken together, all these elements combine to create a vicious cycle producing oxidative particles, accelerating aging, and contributing to chronic diseases like high blood pressure and diabetes.

Protective clothing, sunscreen, whole foods, smoking cessation, exercise, metformin, ACE inhibitors, statins, aldosterone blockers, all reduce oxidative particle generation thereby slowing aging and reducing chronic disease development and progression.

These interventions, based on the science of molecular, are all available today. Some are within the control of the individual (diet and exercise) others, such as prescription medications, require partnership with your primary care physician.



Powerful evidence exists today that shows simple treatments that interfere with ROS generation can make a big difference.

Type 2 diabetic patients with small amounts of protein in the urine are already high risk. A multifactorial intervention combining diet, smoking cessation, metformin, a statin, an ACE inhibitor (lisinopril), or an ARB (losartan), and aspirin was highly effective when compared with usual care using any medication approved to treat the risk factor. There was a 4-fold reduction in heart attack, a 5-fold reduction in stroke, and a 6-fold reduction in dialysis etc. All these treatments are antioxidants that work.

Type 2 diabetic patients in usual care lose 10 years of life expectancy—unless they are on metformin. Diabetics on metformin live a little longer than normal people. We now have proof that medications and lifestyle interventions that reduce oxidative stress have a dramatic impact in combination. You can be healthier longer and live much more normally as you age. Simple, inexpensive interventions can make the difference.

Other articles in this series:

Healthy Life Extended by Eight Years in a Landmark Study

Heart Attacks: When Will We Finally Do What Needs to Be Done

Is There Really a Way to Reverse Diabetes?

Erectile Dysfunction: Is It a Sign of Heart Disease?

Why We Need to Unlock the Full Potential of Primary Care

Reshaping Healthcare: What We Can Learn From Alaska


William H. Bestermann, Jr., MD

William H. Bestermann Jr., MD is a board-certified internist who has practiced preventive cardiology for more than 20 years. His core expertise is consistently producing optimal medical therapy (OMT) for cardiovascular and related conditions. He does this by using evidence-based care processes consistent with best practices.

He looks at OMT as a product. He understands how health care organizations can combine new systems, new science, and new payment models to produce that product much more consistently. That combination can be standardized, scaled, and industrialized. These new systems combine teams, protocols, population health tools, clinical/financial analytics, and provider training. Certain clinical interventions reduce clinical events more than they impact the target risk factor.

Dr. Bestermann has developed integrated protocols that combine those interventions which maximize impact on weight reduction, minimize drug interactions, and reduce side effects. When these systematic interventions are combined, they dramatically reduce the cost of care, prolong life, and delay cardiovascular events.

Dr. Bestermann wrote the first article on a systematic, integrated approach to the metabolic syndrome. He collaborated later with multiple academics and community leaders in a more detailed article on metabolic syndrome science and treatment. He proposed a new mechanism of action for metformin explaining its impact on cardiovascular, events, cancer, and aging.

He supervised an advanced medical home team within Holston Medical Group for cardiometabolic conditions that contained an ambulatory care residency for PharmDs. The team managed high-risk diabetic and hypertensive employees of Eastman Chemical Company.

He is also a senior clinical advisor for the Quality Blue Primary Care initiative at BCBS of Louisiana. That effort reduced hospital admissions, length of stay, and specialty referrals while lowering per member per month costs. He has personal experience producing OMT in multiple medical settings.

He has become convinced that only evidence, data, and transparency can deliver us from the low-value healthcare that prevails across the United States. There are many vendors making claims regarding their clinical and financial success. Most of those claims are not valid. Almost no one is consistently applying optimal medical therapy to patients with cardiovascular and related conditions in a way that prolongs life, delays cardiovascular events and reduces costs. Dr. Bestermann submitted his approach to the Validation Institute and received their stamp of approval.

In addition to being a contributing author for The Doctor Weighs In, Dr. Besterman also serves on the TDWI Editorial Board, where he medically reviews articles submitted for publication.


  • We should be aware of this illness as well as aging. Thanks for sharing this great article.

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