Age-related dysfunction of the DNA damage response in intestinal stem cells
書誌事項
- 公開日
- 2019-04-26
- 資源種別
- journal article
- 権利情報
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- http://creativecommons.org/licenses/by/4.0/
- http://creativecommons.org/licenses/by/4.0/
- DOI
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- 10.1186/s41232-019-0096-y
- 公開者
- Springer Science and Business Media LLC
説明
Senescence increases the risks of inflammatory bowel diseases and colon cancer. Intestinal stem cells (ISCs) in crypts differentiate into epithelial cells and thereby maintain intestinal homeostasis. However, the influence of aging on the functions of ISCs is largely unknown. The mutation rate is highest in the small and large intestines. Numerous types of naturally occurring DNA damage are removed by the DNA damage response (DDR). This response induces DNA repair and apoptosis; therefore, its dysregulation leads to accumulation of damaged DNA and consequently cellular dysfunctions, including tumorigenesis. This study investigated whether aging affects the DDR in mouse ISCs.Young (2-3-month-old) and old ( 19-month-old) Lgr5-EGFP-IRES-creERT2 mice were irradiated. The DDR in Lgr5-positive ISCs was compared between these mice by immunohistochemical analyses.Induction of DDR marker proteins (phosphorylated ATR and 53BP1), inflammatory factors (phosphorylated NF-κB and interleukin-6), and a mitochondrial biogenesis-associated gene (peroxisome proliferator-activated receptor-γ coactivator 1α) was lower in old ISCs than in young ISCs in vivo.The competence of the DDR in ISCs declines with age in vivo.
収録刊行物
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- Inflammation and Regeneration
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Inflammation and Regeneration 39 (1), 2019-04-26
Springer Science and Business Media LLC
