FOR IMMEDIATE RELEASE
UC IRVINE RESEARCHER IDENTIFIES MOLECULAR PROCESS IN CELLS THAT PLAYS CRUCIAL ROLE IN AGING
Study Provides New Insight for Scientists Seeking Ways to Improve Quality of Life for the Elderly, Stretch Life Spans
Irvine, Calif., Feb. 8, 1999 -- A UC Irvine researcher has identified a key molecular process in white blood cells that helps lead to the "wear and tear" taken for granted as part of getting older. Understanding this fundamental process could help scientists find ways to arrest the changes that occur in aging cells, eventually helping people avoid many signs of aging and perhaps even lengthening life spans.
Dr. Sudhir Gupta, professor of medicine at UCI's College of Medicine, describes in the Feb. 15 Journal of Immunology how white blood cells called T lymphocytes become more sensitive to the influences of enzymes and other chemicals as the cells grow older. T lymphocytes are part of the body's immune system, crucial to fighting infections and cancer and ridding the body of dead cells and microscopic foreign objects.
Gupta's study found that the increasing sensitivity of these T cells in aged study participants gradually altered their normal cellular cycles of life and death so that, ultimately, more cells were dying than were being replenished. This overall increase in cell death results in the physiological changes people experience when they grow older, including weakened immune systems, skin wrinkling, memory loss and menopause.
Gupta and his research team compared blood samples taken from 15 men in their 20s with samples from 15 men ages 65-95. The researchers looked at a chemical messenger called Tumor Necrosis Factor (TNF), which is named for its ability to kill cancerous cells but also regulates the life and death cycles of normal cells. TNF attaches itself to receptor sites that exist on nearly all cells. The team found that TNF binds more easily to normal cells as they age, marking them for death. TNF then stimulates another group of chemicals called caspases, which act as "executioners," damaging DNA within cells and destroying them.
The researchers found that more T lymphocytes died in older participants than in the younger ones because the T lymphocytes were made more sensitive to caspase by TNF.
The findings mark the first time scientists have been able to pinpoint the molecular relationships that are responsible for increased death of T lymphocytes in aged study participants, Gupta said. Previous research has shown that reduced T lymphocyte levels result in increased susceptibility to infections, cancer and memory loss, among other disorders.
"We've known that levels of TNF increase in humans as they age. But until now, we didn't know exactly how this process accelerated the cycles of cellular life and death in the aged," Gupta said.
Gupta and his research team concentrated on the workings of a process called "apoptosis" that determines whether cells live or die. Apoptosis occurs in all cells at all stages of life, including fetal development. It keeps bodily systems running smoothly, removing superfluous, infected or damaged cells by causing those cells to commit suicide.
Apoptosis occurs in different parts of the body at different stages of life and is regulated by a number of enzymes and other chemicals. It occurs in early development, such as when a tadpole's tail disappears as it matures into an adult frog. During later stages of life, it is what causes ovaries to experience the effects of menopause or the brain to deteriorate to the point of memory loss. When apoptosis kills off too many cells, it contributes to many diseases, including Alzheimer's disease and AIDS.
By learning how these chemical mechanisms work, scientists hope to find a way to arrest seemingly inevitable aging processes, Gupta noted. The next step is finding a way to make the receptors on cells less sensitive to TNF and to slow the action of the caspases in order to protect older people from the effects of these "executioner" chemicals.
"During the 19th Century, a normal life span was considered to be about 40 years. It's double that now, and it's conceivable that we could make it even longer, or at least healthier," Gupta said. "If you can manipulate the rate of cell death, the immune system remains strong and cells do not die as quickly as during what we consider the normal aging process, improving the quality of life as we age."
But before these findings result in a cellular fountain of youth, researchers will need to determine exactly how much TNF and caspases are necessary to sustain a healthy existence. While these two chemicals contribute to aging, they also protect the body by killing cancer cells.
"T lymphocytes are a fundamental key to maintaining life, but they're affected by many other factors. You need to strike a delicate balance between having just enough apoptosis to sustain a healthy, long life, and also prevent the body from developing cancer," Gupta said.
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Contact:
Andrew Porterfield
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