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Rapid telomere shortening in children
S L Zeichner1, P Palumbo, Y Feng
1HIV and AIDS Malignancy Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. zeichner@nih.gov
Insights
Infant telomere shortening is fourfold higher than in adults, indicating accelerated cell division. This rapid cell division may explain higher viral loads and faster disease progression in infants with human immunodeficiency virus (HIV).
Area of Science:
- Cellular biology
- Developmental biology
- Immunology
Background:
- Telomere shortening is linked to cellular division and aging.
- Human immunodeficiency virus (HIV) impacts actively dividing cells.
- Infants with HIV exhibit distinct disease characteristics compared to adults.
Purpose of the Study:
- To investigate the rate of telomere shortening in infants.
- To compare infant telomere shortening rates with those of adults.
- To explore the implications of infant cell division rates on HIV pathogenesis.
Main Methods:
- Longitudinal collection of peripheral blood mononuclear cells (PBMCs) from nine infants over 3 years.
- Measurement of telomere length and calculation of shortening rates.
- Analysis of correlation between telomere shortening and telomerase activity.
Main Results:
- The average rate of telomere shortening in infant PBMCs was 270 bp per year, over fourfold higher than in adults.
- No correlation was found between telomere shortening and telomerase activity in infants.
- Telomere loss rate changes during development, suggesting periods of accelerated cell division.
Conclusions:
- Infancy is characterized by significantly accelerated cell division compared to adulthood.
- Accelerated cell division in infants may contribute to increased susceptibility and more severe outcomes in HIV infection.
- Understanding telomere dynamics in early life is crucial for pediatric HIV/AIDS research.
Abstract:
Telomere shortening may reflect the total number of divisions experienced by a somatic cell and is associated with replicative senescence. We found that the average rate of telomere shortening in peripheral blood mononuclear cells (PBMCs) obtained longitudinally from nine different infants during the first 3 years of life (270 bp per year) is more than fourfold higher than in adults and does not correlate with telomerase activity. These results show that the rate of telomere loss changes during ontogeny, suggesting the existence of periods of accelerated cell division. Because human immunodeficiency virus (HIV) preferentially infects actively dividing cells, our observation suggesting accelerated cell division in children may provide an explanation for some of the distinctive pathogenic features of the HIV disease in infants, including higher viral loads and more rapid progression to acquired immunodeficiency syndrome (AIDS).