Oxygen and Aging
Is oxygen our friend or our enemy?
Posted September 28, 2016
Two oxygen atoms were walking along the street when one stops and says, “Oh my goodness, I feel more radical. I think I've lost an electron!” “Are you sure?” asks his companion. "Yes," replies the first oxygen atom. "I'm positive."
Old chemistry joke
Every cell in our body needs oxygen to survive; deprived of oxygen for only a few minutes can produce irreversible damage and cell death. At the same time some forms of oxygen are toxic to cells and may produce a significant amount of the cellular injury we associate with aging. This division between the productions of life saving energy or life threatening damage depends on how our cells handle the oxygen. Let’s examine this process in some detail because this distinction has considerable relevance to our own aging.
Tiny structures inside cells called mitochondria are little power plants that burn oxygen and fats or sugar to produce adenosine triphosphate (ATP) which acts like a chemical storage battery to supply energy for most cellular activities. Mitochondria unite oxygen with two hydrogen atoms to form water during this chemical progression. While the process of oxygen utilization is generally well controlled, one side effect is the creation of toxic oxygen “pollutants” called reactive oxygen species or oxygen free radicals. A free radical is a molecule that has lost an electron from one or more of its atoms. Electrons are much more stable in pairs so our unstable oxygen free radical with only one electron shamelessly steals any electron from any nearby source to reunite the pair. This creates another unstable molecule (the one victimized by the oxygen free radical) that then joins avidly with other molecules in a chemical chain reaction called oxidation. Rusting of metal is a familiar example of oxidation.
Under controlled settings oxidative reactions are extremely useful in maintaining our health. For example, our white blood cells release reactive oxygen species in a process called the respiratory burst to kill bacteria and to neutralize ingested particles. However, if not contained and controlled, free radicals can cause widespread damage to proteins, cell membranes and DNA.
Our mitochondria are the main locus of free radical production and are therefore the primary sites of oxidative damage. With increasing mitochondrial injury cellular energy production goes down and free radical generation goes up, creating a vicious cycle. Eventually the oxidative damage is so extensive in our cells and tissues that cellular processes begin to decline. Free radicals and the damage they produce have been implicated in aging, and a number of conditions including malignancy, Alzheimer’s disease, Parkinson’s disease, schizophrenia, certain muscle diseases, cataracts, deafness and cardiovascular disease.
Our body also is exposed to free radicals produced in the environment by sun exposure, manufacturing and cigarette smoke. Not surprisingly our bodies have evolved to use an elaborate array of antioxidant chemicals such as vitamins C and E and beta carotene and cellular enzymes such as superoxide dismutase (SOD), catalase and glutathione peroxidase to quench free radicals and minimize the damage. However no defense is perfect all of the time and some free radical damage does inevitably occur eventually leading to cellular aging and cell death.
Biochemist Denham Harman, M.D., who had worked on petroleum based free radicals as a research chemist for Shell Oil Company, proposed this free radical theory of aging in 1956. Subsequent studies of antioxidants and cellular enzymes such as SOD provided significant support for this theory. The maximal lifespan of a variety of mammals is directly correlated with the amount of SOD. SOD converts an oxygen free radical into hydrogen peroxide which is further metabolized into normal oxygen and water. Mice inbred to knock out SOD have a reduced lifespan and develop malignant diseases such as liver carcinoma and a number of degenerative conditions such as early cataracts and muscle loss. Human mutations of SOD can cause amyotrophic lateral sclerosis (Lou Gehrig’s disease). Other studies report a 30 percent life extension in fruit flies by inserting extra copies of the SOD gene. High levels of SOD are evident in long-lived nematodes. In one compelling study nematodes had significant life extension when synthetic antioxidants were added to their growth medium. Studies of worms in which the genetics of aging has been well worked out have not shown any life extending properties of SOD. It remains unclear for humans whether a diet rich in antioxidants or antioxidant supplementation, in the absence of exercise or other strategies to compensate for free radical production, can reduce disease and extend life.
Exercise and good nutrition are the two most important tools we have in preventing the increased free-radical damage associated with aging. Initiating an exercise program after the antioxidant potential of the body has been reduced by aging actually can reverse some of the losses. Exercise increases the efficiency of oxygen utilization and reduces the number of free-oxygen radicals by boosting our body’s antioxidant defense system. This system is composed of numerous chemical processes that quench or neutralize free-radicals. These adaptive changes occur in parallel with other adaptations to exercise.
Strenuous exercise actually increases the production of free-radicals but regular physical exercise protects against free radical damage by boosting the defenses to a greater extent. The important point is that intense episodic exercise by a “weekend warrior” who usually is sedentary and is out of shape can overwhelm the antioxidant defenses. This circumstance results in increased free-radical damage and may do more harm than good. The key is to build up an exercise program systematically and it is even more important to exercise every day. The net result can be a reduction of free radical damage combined with enhanced growth and repair mechanisms.