Anti-aging and antioxidants

Aging is hard to precisely define, but generally represents a decline in the efficiency of physiological cellular processes after the reproductive phase of life.

For forty years aging was felt to be genetic. Delayed expression of genes were assigned the power to unfold after the reproductive years resulting in aging, cancer, and death. Scientists have been charmed by the power of the double helix.

Yet the power of environment is easily demonstrated by the simple fruit fly (Drosophila) which only lives 14 days at room temperatures (30^oC). But lower the temperature to 10^oC the fruit fly now lives 120 days. This is an 857% increase in life expectancy caused by an environmental change.

In medical school I was taught that one third of illnesses are genetic, one third is due to environment (including infections and diet), and one third is due to unknown factors. Today, I do not believe that genes are static. I believe they are constantly responding to environmental cues with variable effect. When the response in anemic, the result is damage which is cumulative and called aging.

In 1956 Denham Harman proposed the a free-radical theory of aging. By this Dr. Harman suggested random damage to tissues from environment events resulted in free radical production which damage the tissue which was cumulative. Dr. Harman focused on the mitochondria inside cells which produced the energy that runs the cell, is the source of free-radical production and damage. He labeled these free radicals as reactive oxygen species or ROS. Thus began the oxidative damage theory of aging.

Harman's Theory has many attractive features such as:

1) ROS are produced during normal function of the cell and the cell has natural antioxidant defenses.

2) ROS production is under some genetic influence, explaining somewhat why some families live longer.

3) As an animal ages, there is cumulative damage related to prior ROS production, explaining why some family members die inordinately younger due to an unexpected event such as bird flu.

4) There is an inverse correlation between basal metabolic rates of animals and their life span. Generally, larger animals consume less oxygen per pound than small animals, so they live longer.

5) Higher oxygen consumption, such as obesity and excessive activity (eg flying) causes more metabolic production of ROS and shorten life span. To some extent being a thin couch potato should live longer that an obese hyperkinetic person.

6) Natural antioxidant protective mechanisms exist more robustly in longer-lived species. For example the naturally occurring antioxidant SOD (superoxide dismutase) in the liver of humans has much higher concentration than in the liver of all other primates. The relative life span of primates correlates with the relative SOD levels in the liver.

7) Some species have different genetically determined metabolic rates. For example the rat, which typical lives 3 years while the similar sized pigeon lives an amazing 30 years. This exception to the rule of size can be explained by the fact that pigeon mitochondrial DNA generates ROS more slowly by a factor of ten.

8) Manipulation of the status of free radicals in the cell by use of anti-oxidants. This is the fantastic news about the oxidative damage theory of aging! For example vitamin E prolongs the life span of several species such as fruit flies, nematode worms and the rotifer Philodina. In more complex animals the improvement in live span has been elusive. Simple administration of a single antioxidant does not seem helpful, because the body compensates. For example female rats were given the synthetic antioxidant BHT (butylated hydroxytoluene) results in a reduction in the liver vitamin E content. In a more pragmatic study, the use of either vitamin C alone or vitamin E alone had no effect on the onset of Alzheimer's disease in 5,092 seniors in a county in Utah. But it was found that use of high potency and high dose combinations of antioxidant vitamins resulted in a 78% risk reduction in onset of Alzheimer's disease over four years of study.³ Multi-vitamins or individual vitamins were ineffective.

1. Harman D. Free radical involvement in aging. Drugs & Aging. 1993; 3:60 -
2. Sohal RS and Weindruch R. Oxidative stress, caloric restriction and aging. Science. 1996; 273: 59 - .