Scientists Report Rapid Telomere Shortening in Infants

National Cancer Institute
Thursday, 29 April 1999

In the May issue of the journal Blood*, scientists report seeing rapid shortening of telomeres in young, healthy children. This month's finding builds on a growing body of work on telomeres, highly repetitive sequences of noncoding DNA that form the tip at each end of a chromosome. Telomeres are thought to protect chromosomes, like the plastic caps on the ends of shoe laces, keeping them from fraying and improperly recombining with other chromosomes during cell division.

Researchers first noticed over 25 years ago that telomeres shrink slightly in length after each cell division. Further studies led scientists to propose in 1990 that telomere shortening might be the molecular equivalent of aging within a cell. After completing several rounds of cell division, the telomeres become so short that they no longer are functional, signaling the cell to stop dividing and die of old age.

In recent years, several studies have generated strong evidence in adults to support this theory. However, few studies have looked at the rate of telomere shortening in young children, nor have any looked at the process in small children over several years, making this month's report important in helping to establish a baseline of information on the subject.

Steven Zeichner, M.D., Ph.D., a scientist at the National Cancer Institute (NCI) and lead author of the study, and his colleagues hypothesized that if rates of cell turnover vary during development, then telomere shortening -- as a measure of the aging process in cells -- should be greatest in small children. To test this idea, the scientists analyzed the rate of telomere shortening in nine children over three years. All of the children had HIV-positive mothers, although none of the children contracted the virus in utero.

The hypothesis turned out to be correct. The rate of telomere shortening in the children was on average 270 bases, or units, of DNA per year. In adults, the average annual rate is about 50 bases, or about five or sixfold less than small children, a strong indication that immune cells turn over faster in children than adults.

In addition, the scientists found that the changes in telomere length were unrelated to the activity of the enzyme telomerase, which can influence telomere shortening. They reported that levels of the enzyme varied and were in general low among the children. "This suggested to us that the changes in telomere length may indeed reflect the number of cell divisions that the cells had undergone," said Zeichner.

This finding provides an important new lead to explain why HIV-infected infants often progress more rapidly to AIDS than adults. The data suggest that the more rapid rate of cell division in small children gives the virus a larger pool of cells to infect. "This is still only a theory, but it provides a rational explanation for the higher blood levels of HIV that are seen in children and thus their more rapid progression to AIDS," said Dimiter Dimitrov, Ph.D., Sc.D., also an NCI scientist and senior author of this study.

The finding that telomeres shorten rapidly in infants may also have some implications for our understanding of how the immune system develops. When a baby is born, its immune system is only partially developed. But, usually within a few years, the child's immune system has developed the same capacity as an adult to mount an immune response. The finding that in small children immune cells divide much faster than in adults suggests a way for the immune system to accelerate its growth and development.

"By replacing immune cells at a faster rate than adults, a small child rapidly develops immunity, allowing the immune system to mature quickly and protect the body from pathogens," said Zeichner.

* The title of the study is "Rapid Telomere Shortening in Children," article dated May 1, 1999. The authors are Steven L. Zeichner, Paul Palumbo, YanRu Feng, Xiadong Xiao, Dennis Gee, John Sleasman, Maureen Goodenow, Robert Biggar, and Dimiter Dimitrov.

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