Why Humans Age Theory 1: Free Radicals

WEAR AND TEAR: THE FREE RADICAL THEORY OF AGING:

There are many reasons why we become ill, from smoking, to being overweight, to infection. But why do we grow old? There are two keys processes which cause us to grow physiologically older. First is the wear and tear of daily existence, damage which accumulates from the processes of being alive. The most important of these is caused simply by breathing. The oxygen we breath is used to oxidize, or burn, foodstuffs to make energy. In the process, unpaired electrons known as free radicals are released, setting off uncontrolled chain reactions which damage the molecules of which we are made – damage which evidence shows may cause many of the age-associated diseases like cancer, heart disease, Alzheimer’s, cataracts, and many others. There are definite steps we can take to slow this process – antioxidant nutrients appear to be key in maintaining optimal health.

The free radical theory of aging is now accepted by most scientists as the basis of human aging. It states simply that our bodies rust out just like cars – the oxygen we breathe sets off chain reactions via oxyradicals, free radicals or electrons, released primarily from oxygen as it reacts in our mitochondria with food to generate energy, which damage critical molecules from which are bodies are made:

DNA – the genetic information

proteins – the structural building blocks and enzymes which regulate the reactions in our bodies

lipids – the oil-soluble molecules which make up our cell membranes

Products of this damage have been detected and shown to accumulate as we age, including

1) DNA mutations which can cause cancer,

2) lipofuscin which is a clump of protein and lipid caused by free radicals which crosslink these molecules so they cannot be degraded;

3) damaged mitochondria, the powerhouse of the cell where energy is generated, which become less efficient and release more free radicals with age

4) plaque in our arteries, which has been shown to be generated as a result of free radical oxidation of low density lipoproteins, or LDL – the bad form of cholesterol. The oxidized LDL particles are attacked by cells which become foam cells which then stick to our arteries and result in plaque.

Much of this damage appears to be slowed by antioxidants, which is why so many people have become interested in taking them, and why so much scientific research and controversy surrounds these exciting molecules. Antioxidants and careful lifestyle decisions offer us the opportunity to maximize our chances of good health to a ripe old age.

But won’t we eventually still grow old and die? This depends upon our ability to control our genetic basis of aging.

INTERESTING REFERENCES

Beckman, KB, and Ames, BN, “The free radical theory of aging matures”, Physiol. Rev. 78: 547-81 (1998)

“The free radical theory of aging, conceived in 1956, has turned 40 and is rapidly attracting the interest of the mainstream of biological research….During the past decade, several lines of evidence have convinced a number of scientists that oxidants play an important role in aging…The only disadvantage of the current intellectual ferment is the difficulty in diegesting the literature.”

Marsa, L., “Cellular Terrorism”, Longevity, pg 39-42 (May, 1989)

“Free radicals may also cause or contribute to more than 60 of the degenerative illnesses that accompany aging. Some examples: heart disease…stroke…atherosclerosis, emphysema… cataract… Parkinson’s disease and Alzheimer’s disease”

“It’s been over thirty years since the free-radical theory of aging was first formulated by Denham Harman, a chemist turned physician.” “Studies show that free radicals attack the LDL and turn it into a form that penetrates vessel walls all too easily, explains Alex Sevanian, Ph.D….at USC. ‘The resulting accumulation of fat-filled cells along the artery walls is characteristic of the early stages of atherosclerosis.'”

“Free radicals are also now implicated in the heart muscle damage during heart attacks and the brain damage following strokes. When blood flow to the heart – or other tissues- is temporarily disrupted, oxygen free radicals are unleashed when the blood flow is restored. This free-radical reaction – not the actual attack itself – may cause much of the destruction to the heart.”

“There’s no question in my mind that free-radical reactions are the basic cause of aging”, concludes Denham Harman.

Fleming, J.E., Miquel, J. Cottrell, S.F., Yengoyan, L.S., and Economos, A.C., “Is Cell Aging Caused By Respiration-Dependent Injury To The Mitochondrial Genome?”, Gerontology 28:44-53 (1982)

“…the mitochondria of fixed postmitotic cells…may be the site of intrinsic aging because of attack by free radicals and lipid peroxides originating in the organelles as a by-product of the reduction of oxygen during respiration.”

Malins, D.C., Holmes, E.H., Polissar, N.L., and Gunselman, S.J., “The Etiology of Breast Cancer”, Cancer 71:3036-43 (1993)

” Substantial hydroxyl radical induced base lesions, recently found in the DNA of invasive ductal carcinoma of the female breast, are likely to be intimately related to oncogenesis.”

“High concentrations of a number of these lesions were initially found in naturally occurring cancers…of the female breast.”

Harman, D. “The aging process”, PNAS USA 78:7124-7128 (1981)

Explains free radical theory and evidence for it. “It is not unreasonable to expect on the basis of present data that the healthy life span can be increased by 5-10 or more years by keeping body weight down…while ingesting diets adequate in essential nutrients but designed to minimize random free radical reactions in the body.”

Nov, 2002