Linked Life Data

14643186

Source:http://linkedlifedata.com/resource/pubmed/id/14643186

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2003-12-3
pubmed:abstractText
We have previously demonstrated that telomeres shorten more rapidly in peripheral mononuclear cells (PBMC) of infants than in adults (Zeichner et al., Blood 93 (1999) 2824). Here we describe a mathematical model that allows quantification of telomere dynamics both in infants and in adults. In this model the dependence of the telomere dynamics on age is accounted by assuming proportionality between the body growth, as approximated by the Gompertz equation, and the increase in the number of PBMCs. The model also assumes the existence of two subpopulations of PBMC with significantly different rates of division. This assumption is based on the results from a previous analysis of in vitro data for telomere dynamics in presence of telomerase inhibitors and our recent data obtained by measurements of BrdU incorporation in T lymphocytes in humans (Kovacs et al., J. Exp. Med. 194 (2001) 1731). The average telomere length of PBMC was calculated as the average length of these two subpopulations. The model fitted our experimental data well and allowed to derive a characteristic time of conversion of the rapidly proliferating cells to slowly proliferating cells on the order of 20 days. The half-life of the slowly proliferating cells was estimated to be about 6 months, which is in good agreement with data obtained by independent methodologies. Comparison of the one-population and two-subpopulations models demonstrated that one population model cannot explain the observed parameters of the terminal restriction fragment (TRF) dynamics while two-subpopulations model does. These results suggest that the rapid telomere shortening in infants is largely determined by the faster PBMC turnover compared to adults. This may have major implications for elucidation of the HIV pathogenesis in infants. One can speculate that the more rapid course of the HIV disease in infants is due to the existence of rapidly dividing cells, which are susceptible to HIV infection. In addition, these results could have implications for understanding of mechanisms of aging.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0022-5193
pubmed:author
pubmed:issnType
Print
pubmed:day
21
pubmed:volume
226
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
169-75
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
A kinetic model of telomere shortening in infants and adults.
pubmed:affiliation
NCI-Frederick, NIH, Bldg. 469/Rm. 110, P.O. Box B, Frederick, MD 21702-1201, USA. sidorovi@ncifcrf.gov
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S.