Stomach cells replace every 2-9 days

cells replace.JPG

How can the replacement rates of the cells in various tissues in our body be measured? For rapidly renewing tissues common labeling tricks can be useful as with the nucleotide analog BrdU. But what about the very slow tissues that take years or a lifetime? In a fascinating example of scientific serendipity, Cold War nuclear tests have come to the aid of scientists as a result of the fact that they changed the atmospheric concentrations of the isotope carbon-14 around the globe. These experiments are effectively pulse-chase experiments but at the global scale. Carbon-14 has a half-life of 5730 years, and thus even though radioactive, the fraction that decays within the lifetime of an individual is negligible and this timescale should not worry us. The “labeled” carbon in the atmosphere is turned into CO2 and later into our food through carbon fixation by plants. In our bodies, this carbon gets incorporated into the DNA of every nascent cell and the relative abundance of carbon-14 remains stable as the DNA is not replaced through the cell’s lifetime. By measuring the fraction of the isotope carbon-14 in a tissue it is possible to infer the year in which the DNA was replicated as depicted in Figure 1. The carbon-14 time course in the atmosphere initially spiked due to bomb tests and then subsequently decreased as it got absorbed in the much larger pools of organic matter on the continents and the inorganic pool in the ocean.  As can be seen in Figure 1, the timescale for the exponential decay of the carbon-14 in the atmosphere is about 10 years. The measured dynamics of the atmospheric carbon-14 content is the basis for inferring the rates of tissue renewal in the human body and yielded insights into other obscure questions such as how long sea urchins live and the origins of coral reefs.

Using these dating methods, it was inferred that fat cells (adipocytes) replace at a rate of 8±6% per year (BNID 103455). This results in the replacement of half of the body’s adipocytes in ≈8 years. A surprise arrived when heart muscle cells were analyzed. The long held dogma in the cardiac biology community was that these cells do not replace themselves. This paradigm was in line with the implications of heart attacks where scar tissue is formed instead of healthy muscle cells. Yet it was found that replacement does occur albeit at a slow rate. Estimates vary from 0.5% per year (BNID 107076) to as high as 30% per year (BNID 107078) depending on age and gender (BNID 107077). A debate is currently taking place over the very different rates observed, but it is clear that this peculiar scientific side-effect of Cold War tensions is providing a fascinating window onto the interesting question of the life history of cells making up multicellular organisms.


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