GHR15

In Search of the Secrets of Aging
Condensed from the Government Report by the National Institute on Aging

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One hundred and twenty years, as far as we know, is the longest that anyone has ever lived. A man in Japan, Shirechiyo Izumi, reached the age of 120 years, 237 days in 1986, according to documents that most experts think are authentic. He died after developing pneumonia.

Long lives always make us wonder: What is the secret? Does it lie in the genes? Is it where people live or the way they live -- something they do or do not do? Eat or do not eat? Most of the scientists who study aging, gerontologists, say the secret probably lies in all of the above -- heredity, environment, and lifestyle.

But gerontologists also ask other and more difficult questions. For example, if the 120-year-old had not finally succumbed to illness, could he have lived on and on? Or was he approaching some built-in, biological limit? Is there a maximum human life span beyond which we cannot live no matter how optimal our environment or favorable our genes?

Whether or not there is such a limit, what happens as we age? What are the

dynamics of this process and how do they make life spans short, average, or long? Once we understand these dynamics, could they be used to extend everyone's life span to 120 or even, as some scientists speculate, to much greater ages?

And finally for all of us, the most important question: How can insights into longevity be used to fight the diseases and disabilities associated with old age to make sure this period of life is healthy, active, and independent?

Average life span and life expectancy in the United States have grown dramatically in this century, from about 47 years in 1900 to about 75 years in 1990. This advance is mostly due to improvements in sanitation, the discovery of antibiotics, and medical care. Now, as scientists make headway against chronic diseases like cancer and heart disease, some think it can be extended even further.

Maximum human life span seems to be another matter. There is no evidence that it has changed for thousands of years despite fabled fountains of youth and biblical tales of long-lived patriarchs. However, very recently, the dream of extending life span has shifted from legend to laboratory. As gerontologists explore the genes, cells, and organs involved in aging, they are uncovering more and more of the secrets of longevity. As a result, life extension may now be more than the stuff of myth and the retardation of disease and disability, realistic goals.

Hormones

In 1989, at Veterans Administration hospitals in Milwaukee and Chicago, a

small group of men aged 60 and over began receiving injections three times a week that dramatically reversed some signs of aging. The injections increased their lean body (and presumably muscle) mass, reduced excess fat, and thickened skin. When the injections stopped, the men's new strength ebbed and signs of aging returned.

What the men were taking was recombinant human growth hormone (HGH), a synthetic version of the hormone that is produced in the pituitary gland and plays a critical part in normal childhood growth and development. Now researchers are learning that HGH, or the decline of HGH, seems also to play a role in the aging process in at least some individuals.

The idea that hormones are linked to aging is not new. We have long known that some hormones decline with age. Human growth hormone levels decrease in about half of all adults with the passage of time. Production of the sex hormones estrogen and testosterone tends to fall off. Hormones with less familiar names, like melatonin and thymosin, are also not as abundant in older as in younger adults.

Frontiers

New territory, unexplored or only sketchily mapped, lies ahead. As gerontologists isolate and characterize more and more longevity- and aging-related genes in laboratory animals, insights into genes and gene products important in human aging will emerge. Comparable human genes will be identified and mapped to chromosomes.

This information will be useful in designing both genetic and non-genetic interventions to slow or even reverse some aging-related changes. Already, for example, a study by Helen Blau of Stanford University has shown that muscle cells can be genetically modified and injected into muscle where they will produce and secrete human growth hormone. Non-genetic strategies will include the development of interventions to reduce damage to cellular components, such as proteins, nucleic acids, and lipids.

Normal aging will be more closely defined. For instance, at NIA's Gerontology Research Center, the behavior of the cells that line blood vessels during aging is now providing clues to the stiffening of blood vessels that occurs with age as well as insights into vascular disease. As key biomarkers of aging are identified, researchers will be able to use them to test interventions to slow aging. Studies will begin to delve more deeply into differences in aging between the sexes and among ethnic groups.

In short, gerontologists will be charting the paths and intersections of genetic, biochemical, and physiologic aging. What they find will reveal some of the secrets of aging. It may lead to extended life spans. It will very certainly contribute to better health, less disability, and more independence in the second fifty years of life.