Part Two: Key Ideas of the Cellular Damages Theory of Aging (CDTA)

Nancy B. Alston

Part one of this four part article discussed the programmed cellular death theory of aging. The main topic of this article is the cellular damages theory of aging (CDTA). The CDTA approach to anti-aging treatment is to understand and treat the various types of cellular damage associated with aging and closely related diseases. Per this theory the best path to effective anti-aging treatment is to attack the symptoms of aging. Treating symptoms is a successful and useful technique that most doctors use. If the root cause of a medical problem is unknown or too difficult to uncover, doctors will fall-back to treating the symptoms of the problem. The problem itself may or may not go away but good treatment of its symptoms will allow the problem to remain hidden indefinitely. Many of the root causes of aging are not yet understood well enough to be treated directly. This is reflected in a growing trend in anti-aging medicine. Doctors are becoming specialists in treating the specific symptoms of aging but not aging itself. This approach to anti-aging is definitely not the final answer but it is the best that we can do for now. It can add many more productive years to one’s life.

Everyone is constantly exposed to various types of cellular stress. Cellular DNA damage occurs at a rate of many thousands of molecular level disruptions per day. DNA and other repair mechanisms try to correct this damage and the process of apoptosis removes the most badly damaged cells. Healthy cells, when signaled through mitogenic stimulation from neighboring cells, undergo mitosis and divide to replace damaged cells. The process is good but imperfect. Fatal and non-fatal errors can and do occur during many phases of the repair and reproduction processes. In addition to controlling cell division, human cells have evolved complex systems of inter cellular signaling that they rely on to function normally. These signaling systems have to be operating correctly or the cell will act as if it is no longer needed and commit suicide through apoptosis. This is an area of study for CDTA because many cellular regulatory mechanisms, including cellular signaling, weaken and start failing as old age begins manifesting itself.

Other specific types of cellular damages that CDTA studies include: various types of cellular mutations, cross linking and glycation, free radical damage, and the accumulation of cellular waste products. CDTA also tries prevent cellular damages caused by inflammation and oxidative stress. It has been shown that these factors can cause cellular aging by permanently stopping cell reproduction without shortening the length of cellular telomere chains. Most of the types cellular damages described above accumulate with age. Their effects may not be visible when you are young but their net result is that your cells are continuously aging.

Included in CDTA is the free radical theory of aging (FRTA) and its derivative theory, the mitochondrial theory of aging. In simple general terms these theories say is that many of the symptoms of aging are due to uncorrected accumulation of cellular damage caused by free radicals. The key point that free radical damages accumulate with age is now a well accepted idea. Free radicals (highly reactive ionized molecules) are always present and always cause molecular damage. Free radicals are continuously being produced and removed by the human body. Environmental factors (pollution, radiation, cigarette smoke, herbicides etc.) can increase free radical products in the body. Within the body free radical species such as reactive oxygen species (ROS) and reactive nitrogen species (RNS) are by-products of the normal cellular redox process. They are simultaneously both essential and harmful to cellular life. Human tissue cells have to maintain a delicate working balance between these opposite effects. This homeostatic balance is also referred to as the “redox balance”.

There are two popular CDTA anti-aging treatment approaches to slowing the cellular damage caused by free radicals. They are championed by different, somewhat conflicting, camps of people. The smaller camp wants to stimulate the body’s own antioxidant systems. The larger group advocates using significant amounts of external antioxidants such as vitamin C, E and other supplements. I will discuss the differences these groups have in their approaches to anti-aging in my next article but for now a little more background on free radicals and antioxidants might be useful.

Concentrations of free radicals in the body may rise to dangerous levels if they are not neutralized quickly enough. High free radical levels increase oxidative stress in the body which then starts damaging cellular molecules. This type of biochemical stress helps cause many or even most diseases. A very short and incomplete list of such diseases includes: “aging”, chronic and degenerative illness such as autoimmune disorders, cancer, cardiovascular and neurodegenerative diseases (ex. Alzheimer’s Disease), diabetes, cataracts, and rheumatoid arthritis. Antioxidants are continually being used and replenished to keep free radical concentrations within manageable limits. Both internal (endogenous) and externally (exogenous) obtained antioxidants neutralize free radicals and help maintain the radox balance.

Mammalian cells have internal enzymatic antioxidants (Superoxide Dismutase (SOD), Glutathione Peroxidase, Glutathione reductase, various Catalases, and other antioxidants) that form the first line of defense against free radical damage. These enzyme systems require externally provided (diet and supplements) nutritional minerals such as selenium, iron, copper, zinc, and manganese to act as cofactors for optimum catalytic activity. These defenses against free radicals consist of several sensing and signaling mechanisms that activate and deactivate the production of internal antioxidants. One such mechanism is the Nrf2 protein activation system. High levels of free radicals will activate the normally latent Nrf2 protein. Once released, Nrf2 activates the antioxidant Response Element (ARE), also called hARE (Human Antioxidant Response Element). This master regulator of the cellular antioxidant system then increases the production many natural antioxidants. A variety of foods, taken in very modest amounts, can activate Nrf2 and greatly increase the production of natural antioxidants. This includes foods such as: green tea, turmeric, and red wine. Other known Nrf2 activators include lowered oxygen content (hypoxia) and food deprivation (calorie reduction). CDTA experts generally agree with the above descriptions but they disagree on how best to apply this information for anti-aging therapy. The next article in this series will discuss the approaches CDTA has to anti-aging.

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