Sci. Aging Knowl. Environ., 20 July 2005
Vol. 2005, Issue 29, p. nf58
[DOI: 10.1126/sageke.2005.29.nf58]



Radioactive dating reveals cellular ages

Mitch Leslie

Like vain Hollywood stars, our cells have kept their true ages secret. But a new technique similar to the method for dating Egyptian mummies can determine cells' birth dates. Researchers have now used the technique to demonstrate that certain brain cells don't replenish themselves.

Throughout life, the body crafts replacements for cells that wear out quickly, such as those in the skin and intestinal lining. However, researchers debate how much cell turnover occurs in the brain and heart. Experiments with tagged DNA building blocks show that rodents and monkeys create new cells in the brain's hippocampus, which helps etch memories. A study on people detected continuing cell replication, or neurogenesis, in the same area, confirming that adults renew at least some neurons. But the division-marking compounds are poisonous, limiting their use in people--the human study involved terminal cancer patients who had agreed to take one of the markers and underwent a brain autopsy after death. Current techniques haven't allowed scientists to nail down whether new neurons arise in other parts of the brain such as the cortex, which handles problem solving and other "higher functions." Neuroscientist Jonas Frisén of the Karolinska Institute in Stockholm, Sweden, and colleagues devised a technique for determining a cell's birth date that relies on carbon-14, the radioactive isotope that allows archaeologists to pinpoint when pots and manuscripts were created.

Because of aboveground nuclear tests after World War II, the amount of carbon-14 in the atmosphere boomed in the 1950s and early 1960s. After an international treaty forbade the tests in 1963, carbon-14 quantities gradually declined. Cells build carbon-14 into their DNA, so the concentration of the isotope in the molecule indicates when the cells formed. Although the technique isn't sensitive enough to date individual cells, it can determine when a group of cells appeared. Using tissue from autopsies, the team found that cells from the cerebellum, the part of the brain that coordinates movement, were born about the same time as the person they hailed from, suggesting little replacement in this region. However, cells from the occipital cortex, which analyzes visual input, were younger than the people they came from, indicating that some cell division had occurred. When the researchers separated the neurons from support cells called glia, however, they discovered that the neurons hadn't reproduced, suggesting that glial cells were responsible for the turnover. The team plans to analyze other organs for which the amount of cell renewal remains uncertain, such as the heart, says Frisén.

"This is an ingenious strategy" for gauging cell replacement over many years, says developmental neuroscientist Richard Nowakowski of the University of Medicine and Dentistry of New Jersey in Piscataway. Combined with animal studies, the work shows that in the cortex, "neurogenesis doesn't occur under normal conditions during adulthood," says neuroscientist Jeffrey Macklis of Harvard Medical School in Boston. The next step is to apply the technique to measure the long-term amount of cell generation in the hippocampus, says biochemist Marc Hellerstein of the University of California, Berkeley. Researchers might soon know which brain cells act their age.

July 20, 2005
  1. K. L. Spalding, R. D. Bhardwaj, B. A. Buchholz, H. Druid, J. Frisén, Retrospective birth dating of cells in humans. Cell 122, 133-143 (2005). doi:10.1016/j.cell.2005.04.028 [CrossRef][Medline]
Citation: M. Leslie, Bombshell. Sci. Aging Knowl. Environ. 2005 (29), nf58 (2005).

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