Document Detail


Changes in cell-cycle kinetics responsible for limiting somatic growth in mice.
MedLine Citation:
PMID:  18535488     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In mammals, the rate of somatic growth is rapid in early postnatal life but then slows with age, approaching zero as the animal approaches adult body size. To investigate the underlying changes in cell-cycle kinetics, [methyl-H]thymidine and 5'-bromo-2'deoxyuridine were used to double-label proliferating cells in 1-, 2-, and 3-wk-old mice for four weeks. Proliferation of renal tubular epithelial cells and hepatocytes decreased with age. The average cell-cycle time did not increase in liver and increased only 1.7 fold in kidney. The fraction of cells in S-phase that will divide again declined approximately 10 fold with age. Concurrently, average cell area increased approximately 2 fold. The findings suggest that somatic growth deceleration primarily results not from an increase in cell-cycle time but from a decrease in growth fraction (fraction of cells that continue to proliferate). During the deceleration phase, cells appear to reach a proliferative limit and undergo their final cell divisions, staggered over time. Concomitantly, cells enlarge to a greater volume, perhaps because they are relieved of the size constraint imposed by cell division. In conclusion, a decline in growth fraction with age causes somatic growth deceleration and thus sets a fundamental limit on adult body size.
Authors:
Maria Chang; Elizabeth A Parker; Tessa J M Muller; Caroline Haenen; Maanasi Mistry; Gabriela P Finkielstain; Maureen Murphy-Ryan; Kevin M Barnes; Rajeshwari Sundaram; Jeffrey Baron
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Intramural    
Journal Detail:
Title:  Pediatric research     Volume:  64     ISSN:  1530-0447     ISO Abbreviation:  Pediatr. Res.     Publication Date:  2008 Sep 
Date Detail:
Created Date:  2008-08-22     Completed Date:  2008-11-12     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  0100714     Medline TA:  Pediatr Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  240-5     Citation Subset:  IM    
Affiliation:
Section on Growth and Development, National Institutes of Health, Bethesda, MD 20892, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Animals, Newborn
Body Size
Bromodeoxyuridine
Cell Cycle / physiology*
Cell Enlargement
Cell Proliferation*
Hydrogen
Kidney / cytology*,  growth & development*
Liver / cytology*,  growth & development*
Male
Mice
Mice, Inbred C57BL
Organ Size
Thymidine
Time Factors
Tritium
Grant Support
ID/Acronym/Agency:
Z01 HD000640-12/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
10028-17-8/Tritium; 1333-74-0/Hydrogen; 50-89-5/Thymidine; 59-14-3/Bromodeoxyuridine
Comments/Corrections

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