Down syndrome as a model of DNA polymerase beta haploinsufficiency and accelerated aging

@article{Patterson2012DownSA,
  title={Down syndrome as a model of DNA polymerase beta haploinsufficiency and accelerated aging},
  author={David Patterson and Diane C. Cabelof},
  journal={Mechanisms of Ageing and Development},
  year={2012},
  volume={133},
  pages={133-137}
}
Down syndrome is a condition of intellectual disability characterized by accelerated aging. As with other aging syndromes, evidence accumulated over the past several decades points to a DNA repair defect inherent in Down syndrome. This evidence has led us to suggest that Down syndrome results in reduced DNA base excision repair (BER) capacity, and that this contributes to the genomic instability and the aging phenotype of Down syndrome. We propose important roles for microRNA and/or folate… 
The Impact Of Down Syndrome And Folate Depletion On Genomic Stabilizing Pathways Of Lymphoblastoid Cells
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A quantitative molecular marker of aging (known as the epigenetic clock) is utilized to demonstrate that trisomy 21 significantly increases the age of blood and brain tissue in Down Syndrome.
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Changes in the both global and targeted metabolomics in the brains of the Ts65Dn mouse are reported, and long-term treatment with microencapsulated dietary rapamycin changes the metabolomic profiles in a manner consistent with increases in healthspan.
Loss of DNA polymerase β induces cellular senescence
TLDR
It is found that primary fibroblasts from Down syndrome individuals exhibit greater SA‐β‐gal staining, increased p16 transcript abundance, and a robust increase in the number of senescent cells compared to wild‐type, demonstrating that loss DNA polymerase β is sufficient to induce senescence.
Rapamycin Treatment Ameliorates Age-Related Accumulation of Toxic Metabolic Intermediates in Brains of the Ts65Dn Mouse Model of Down Syndrome and Aging
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