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A step away from death

Aproova Mandivilli

People have scaled mountains, composed symphonies, solved complex mathematical problems, written poetry and plays, painted, sculpted, philosophized, explored and conquered the earth and beyond. Yet, one objective eludes their grasp: immortality. Last month, that goal may have inched one step closer when scientists elucidated a mechanism that causes immune cells in an aging individual to die.

A research team at the University of California at Irvine has found evidence that a protein that induces diseased cells to die may also be responsible for the death of aging immune cells. If further research confirms this hypothesis, understanding the pathway could help scientists find a way to keep old age at bay.

"(One of the primary goals of the study) is definitely to see if we can improve the quality of life and prevent the diseases of aging," said Dr Sudhir Gupta, the immunologist, who led the research team at Irvine.

As people age, their immune systems become weaker. What is not clear, however, is if the reason is that "the cells are not functioning or they die faster as we get older," said Dr Gupta.

While the finding by his group is presumably only one small piece of the puzzle that explains why bodies weaken and perish with age, it may clarify why immune systems in older people are more vulnerable to infection and disease.

Tumor Necrosis Factor, a protein produced by many cells in the body, signals cells to enter a sequential pathway that results in the suicide of the cells, a process called programmed cell death, or apoptosis. While healthy cells have mechanisms that help them ignore this signal, cells that are cancerous or otherwise defective often lack these mechanisms and enter apoptosis. TNF is thus part of the cell's defense against the presence of diseased cells and is sometimes referred to as an anticancer protein.

In aging cells, including cells of the immune system, TNF levels in the bloodstream are at higher levels than in young cells of the same type. As they age, immune cells, which normally defend the body against disease, also become less effective at guarding the body against enemy pathogens. Dr Gupta examined the hypothesis that a progressive decrease in the function of immune cells during aging is a consequence of increased TNF levels in the blood.

The study, published in a recent issue of the Journal of Immunology, tested the effects of high concentrations of the protein on young and aging immune cells. To compare the immune cells from young and aging populations, Dr Gupta's team collected blood samples from 15 students and staff between the ages of 20 and 29, and retired professors between 65 and 95 years. They then isolated and established cultures of CD4 and CD8 cells, two important types of immune cells, from each specimen.

In the presence of high levels of TNF, 26 per cent of young CD8 cells and 40 percent of aging CD8 cells committed to self-destruction; CD4 cells showed similar effects. The evidence suggests that exposure to high levels of TNF, such as those seen in aging cells, induces cell death. Aging cells are also more sensitive to TNF than are younger cells of the same type. TNF may thus cause aging immune cells to die at higher rates and contribute to the decline of the body's immune system.

Dr Michael Lotze, an immunologist at the University of Pittsburgh Medical Center, also believes that as cells age, they become more sensitive to TNF-induced cell death. "We have other evidence that confirms (Dr Gupta's) hypothesis," he said. The most interesting question now, Lotze suggests, is why the cells become more sensitive to TNF.

Exposure to TNF is only one of several processes that may induce cells to undergo apoptosis. Exposure to irradiation, heat shock, and certain chemicals can all commit a cell to self-destruction and each may do so via a different series of steps, involving different proteins. Any practical approach to countering this process in aging cells should therefore focus on a step that is common to all these stimulants.

In a country like India where infectious diseases are a major cause of mortality, the well-being of the immune system becomes even more important, says Dr Gupta. Malnutrition and the lack of adequate healthcare contribute to impaired immunity, which in turn contributes to increased levels of TNF and thus to immune cell death, creating a vicious cycle. In those cases, Dr Gupta asserts, the most effective means of prolonging life is through proper nutrition and education.

Understanding the processes that cause immune cells to die could help people counter infectious diseases and cancer, two of the major causes of old age, says Dr Gupta. Through his research, he aims to "prolong the life span, but more importantly, improve the quality of life in old age."

The writer is a graduate student at New York University.

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