AffiliationDepartment of Geriatric Medicine and School of Biological Sciences, University of Manchester, 3.239 Stopford Building, Oxford Road, Manchester, M13 9PT, United Kingdom.
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AbstractCell senescence is seen in many types of differentiated cells but age changes in stem cells have not previously been clearly demonstrated. Changes in stem cells may be of great importance for the ageing process, because any decline with age in the numbers and functional integrity of stem cells can lead to progressive deterioration of function and of proliferative homeostasis in tissues. Stem cells of the murine small intestine provide an excellent model system because these cells occupy a well-defined position near the base of the crypts of Lieberkühn. We examined mice aged between 5 and 32 months and found age-related alterations in the histology of the small intestine and in the apoptotic response of stem cells to low-dose irradiation. Apoptosis in the crypts is concentrated around the stem cell position and can be markedly elevated by exposure to radiation or cytotoxic agents, suggesting that "suicide" of damaged stem cells may be an important system for long-term tissue maintenance. Animals aged 5, 15, 18, and 29 months were exposed to either 1 or 8 Gy gamma irradiation. A twofold increase in the level of apoptosis was seen following 1 Gy gamma irradiation in the 29-month-old animals, compared to the young and middle-age groups. After 8 Gy irradiation the level of apoptosis in all age groups was high and the age effect less pronounced. The data suggest that stem cells do undergo some functional alteration with age.
CitationAge changes in stem cells of murine small intestinal crypts. 1998, 241 (2):316-23 Exp. Cell Res.
JournalExperimental Cell Research
- Ageing of murine small intestinal stem cells.
- Authors: Potten CS, Martin K, Kirkwood TB
- Issue date: 2001
- The relationship between ionizing radiation-induced apoptosis and stem cells in the small and large intestine.
- Authors: Potten CS, Grant HK
- Issue date: 1998 Oct
- Altered stem cell regeneration in irradiated intestinal crypts of senescent mice.
- Authors: Martin K, Potten CS, Roberts SA, Kirkwood TB
- Issue date: 1998 Aug
- Radiation-induced mitotic delay: duration, dose and cell position dependence in the crypts of the small intestine in the mouse.
- Authors: Chwalinski S, Potten CS
- Issue date: 1986 May
- The effects of repeated doses of keratinocyte growth factor on cell proliferation in the cellular hierarchy of the crypts of the murine small intestine.
- Authors: Potten CS, O'Shea JA, Farrell CL, Rex K, Booth C
- Issue date: 2001 May