A protein that helps the body fend off cancer appears to cause the immune system to degenerate in old age. Researchers in California say that as the body ages, protective cells of the immune system become hypersensitive to the protein, and die at higher rates.
Many cells in the body produce tumour necrosis factor (TNF), a protein that helps to destroy diseased cells by triggering the cell's self-destruct mechanism. Most cells ignore the suicide instructions, and even switch on protective mechanisms when exposed to TNF. But infected or cancerous cells should obey the signal, setting loose proteins called caspases that dissolve the nucleus of the cell.
As people age, levels of TNF in their blood rise. Immunologist Sudhir Gupta of the University of California at Irvine wondered if the protein might account, at least in part, for the weakening of the immune system that also comes with age. He and his colleagues collected blood samples from 15 retired professors between the ages of 65 and 95 and from 15 students and staff between 20 and 29. From the samples, they cultured two types of T cells, CD4 and CD8, which work on the immune system's front line to destroy invading or infected cells.
When exposed to TNF, 26 per cent of the CD8 cells from young subjects underwent apoptosis. By contrast, 40 per cent of the aged CD8s committed suicide. The researchers found a similar increase in cell death among the older group's CD4 cells, suggesting they had become more sensitive to TNF (Journal of Immunology, vol 162, p 2154).
Gupta then counted how many T cells from each group had a surface receptor for TNF. These come in two types.Receptor I reads the apoptosis signal from TNF, while receptor II ignores it. Gupta found that in the young volunteers, far more T cells had type II receptors than type I. But the opposite was true in the older subjects.
Rita Effros, who studies the role of the immune system in ageing at the University of California at Los Angeles, says the research is important, but warns that so far no one has traced the decline of the ageing immune system to the death of white blood cells. In ageing mice, for example, the number of white blood cells actually increases. "This is a really good beginning, but there is more work to be done," says Effros.
Gupta agrees that TNF and T cells are not the whole story. He says rates of apoptosis probably increase in many other cell types as well, and many other signals besides TNF are involved. His lab is now studying other cell-death mechanisms. "We want to know as many pathways as possible in ageing," he says.
Gupta's ultimate goal is to discover ways to alleviate some effects of old age. He says drugs that target caspases may help preserve the ageing immune system. "If we can delay the cell-death process, we may improve not just life span but the quality of life in old age."
Author: Jonathan Knight
New Scientist issue 20 February 1999
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