Aging : Antioxidants, Skin

by National Institute on Aging

(Page 7 of 15)

Antioxidants and Aging Nematodes

A worm barely the size of a comma printed on this page may change how investigators think about oxygen radicals, antioxidants, and aging. C. elegans nematodes immersed in a liquid containing a potent antioxidant drug lived 44 percent longer than worms not treated with this substance. It was the first time that any drug had extended the lifespan of any multi-cellular organism. The finding lends credence to the hypothesis that oxygen radicals have a significant role in the aging process.

In addition, the international team of investigators, led by Simon Melov, Ph.D., of the Buck Center for Research in Aging in California, restored a normal lifespan to mutant worms that had a mitochondrial defect, which caused increased oxygen radical production and accelerated aging. The worms showed no apparent ill effects from the treatment.

EUK-134, the drug used in the experiment, was a synthetic form of superoxide dismutase (SOD) and catalase, two enzymes that counteract the effects of oxidative stress. Like other antioxidants, such as vitamin E, these compounds convert oxygen radicals to water. But they are much more potent.

While it is only one study, and its results have not been confirmed in other species, this investigation supports the concept that antioxidant defenses may be critical during aging. It also suggests that one day it may be possible to use similar interventions to treat age-related conditions in humans.

This process, called oxidation, can spark a chain reaction resulting in a series of products, some of which are actually beneficial. The immune system, for instance, uses free radicals to destroy bacteria and other pathogens. Another oxidizing molecule, called nitric oxide, helps nerve cells in the brain communicate with each other.

Free radicals, however, also can be vandals that cause extensive damage to proteins, membranes, and DNA. Mitochondria are particularly prone to free radical damage. The major source of free radical production in the body, they are also one of its prime targets. As the damage mounts, mitochondria become less efficient, progressively generating less ATP and more free radicals. Over time, according to the free radical theory, oxidative damage accumulates in our cells and tissues, triggering many of the bodily changes that occur as we age. Free radicals have been implicated not only in aging but also in degenerative disorders, including cancer, atherosclerosis, cataracts, and neurodegeneration.

But free radicals, which also can be produced by tobacco smoke, sun exposure, and other environmental factors, do not go unchecked. Cells utilize substances called antioxidants to counteract them. These substances including nutrients - the familiar vitamins C and E - as well as enzymes produced in the cell, such as superoxide dismutase (SOD), catalase, and glutathione peroxidase, prevent most oxidative damage. Nonetheless, some free radicals manage to circumvent these defenses and do harm. As a result, cellular repair mechanisms eventually falter and some internal breakdowns are inevitable. These breakdowns can lead to cellular senescence, and eventually may trigger apoptosis, a form of programmed cell death.

Support for the free radical theory, which was first proposed in 1956 by chemist Denham Harman, M.D., comes from studies of antioxidants, particularly SOD. SOD converts an oxygen radical known as superoxide anion into hydrogen peroxide, which can be degraded by an enzyme, called catalase, into oxygen and water. Studies have shown that inserting extra copies of the SOD gene into fruit flies extends their average lifespan by as much as 30 percent.

Other experimental evidence lends support to the free radical hypothesis. For example, higher levels of SOD and catalase have been found in long-lived nematodes. In one compelling study, giving nematodes synthetic forms of these antioxidants significantly extended their normal lifespan.

The discovery of antioxidants raised hopes that people could retard aging simply by adding them to the diet. So far, studies of antioxidant-laden foods and supplements in humans have yielded little support for this premise. Further research, including largescale epidemiological studies, might clarify whether dietary antioxidants can help people live longer, healthier lives. For now, however, the effectiveness of dietary antioxidant supplementation remains controversial. In the meantime, gerontologists are investigating other intriguing biochemical processes affected by free radicals, including protein crosslinking.

Research on Sunlight May Help Explain What Happens to Skin as We Age

As anyone who reads beauty magazines knows, sunlight damages skin in ways that seem similar to aging. It's well-established that long-term, sunlight-induced damage causes wrinkles. And in both normal aging and photoaging - the process initiated by sunlight - the skin becomes drier and loses elasticity. Although gerontologists think that the normal or intrinsic aging process is probably not the same as photoaging, there are enough similarities to make this a tantalizing field of study.

The process of photoaging may hold clues to normal aging because many of the same cells are affected. Photoaging, for example, damages collagen and elastin, the two proteins that give skin its elasticity. These proteins decline as we age, along with the fibroblast cells that manufacture them. In addition, the enzymes that break down collagen and elastin increase.

Other changes occur in keratinocytes, upper-layer skin cells that are shed and renewed regularly. In the normal aging process the turnover of keratinocytes slows down and in photoaging they are damaged. Still other skin cells, called melanocytes, are also affected by both processes: they decline with normal aging and are killed in photoaging. (Stopped in their tracks by sunlight, these normally migratory cells show up as freckles in light skin.)

What we don't know yet is exactly how photoaging damages cells. Ultraviolet light can damage DNA and could be the culprit. Free radicals could be involved in some way. Researchers continue to explore these and other factors in the effort to understand photoaging.

About the Author

www.nia.nih.gov
NIA, one of the 27 Institutes and Centers of NIH, leads a broad scientific effort to understand the nature of aging and to extend the healthy, active years of life. In 1974, Congress granted authority to form NIA to provide leadership in aging research, training, health information dissemination, and other programs relevant to aging and older people.