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Changes in cell-cycle kinetics responsible for limiting somatic growth in mice
Maria Chang1, Elizabeth A Parker, Tessa J M Muller
1Section on Growth and Development, National Institutes of Health, Bethesda, MD 20892, USA.
Pediatric Research
|June 7, 2008
Summary
Somatic growth deceleration in mammals is mainly due to a reduced growth fraction (proliferating cells), not longer cell cycles. Cells enlarge as they approach adult size, limiting further body growth.
Area of Science:
- Developmental biology
- Cell biology
- Mammalian growth
Background:
- Somatic growth rate in mammals slows with age, approaching zero near adult body size.
- Understanding the cellular mechanisms behind growth deceleration is crucial for comprehending adult body size limitations.
Purpose of the Study:
- To investigate age-related changes in cell-cycle kinetics and their impact on somatic growth deceleration in mice.
- To determine whether increased cell-cycle time or decreased cell proliferation contributes more to growth slowdown.
Main Methods:
- Double-labeling proliferating cells in mice of different ages (1, 2, and 3 weeks) using [methyl-H]thymidine and 5'-bromo-2'deoxyuridine over four weeks.
- Quantifying cell proliferation, cell-cycle time, growth fraction, and cell area in renal tubular epithelial cells and hepatocytes.
Main Results:
- Cell proliferation in kidney and liver decreased significantly with age.
- The fraction of cells that will divide again (growth fraction) declined approximately 10-fold with age.
- Average cell area increased approximately 2-fold, while cell-cycle time showed minimal increase.
Conclusions:
- Somatic growth deceleration is primarily caused by a decline in the growth fraction, not an increase in cell-cycle time.
- Cells enlarge and reach a proliferative limit, contributing to the cessation of somatic growth.
- The decrease in growth fraction sets a fundamental limit on adult body size in mammals.
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