دورية أكاديمية
Increasing p16(INK4a) expression decreases forebrain progenitors and neurogenesis during ageing
| العنوان: | Increasing p16(INK4a) expression decreases forebrain progenitors and neurogenesis during ageing |
|---|---|
| المؤلفون: | Molofsky, Anna V., Slutsky, Shalom G., Joseph, Nancy M., He, Shenghui, Pardal, Ricardo, Krishnamurthy, Janakiraman, Sharpless, Norman E., Morrison, Sean J. |
| المساهمون: | Univ Michigan, Dept Internal Med, Howard Hughes Med Inst, Ann Arbor, MI 48109 USA, Univ Michigan, Ctr Stem Cell Biol, Ann Arbor, MI 48109 USA, Univ N Carolina, Sch Med, Lineberger Comprehens Canc Ctr, Dept Med, Chapel Hill, NC 27599 USA, Univ N Carolina, Sch Med, Lineberger Comprehens Canc Ctr, Dept Genet, Chapel Hill, NC 27599 USA, seanjm@umich.edu |
| المصدر: | Nature |
| بيانات النشر: | Nature Publishing Group |
| سنة النشر: | 2006 |
| المجموعة: | University of Michigan: Deep Blue |
| مصطلحات موضوعية: | Science |
| الوصف: | Mammalian ageing is associated with reduced regenerative capacity in tissues that contain stem cells(1,2). It has been proposed that this is at least partially caused by the senescence of progenitors with age(3,4); however, it has not yet been tested whether genes associated with senescence functionally contribute to physiological declines in progenitor activity. Here we show that progenitor proliferation in the subventricular zone and neurogenesis in the olfactory bulb, as well as multipotent progenitor frequency and self-renewal potential, all decline with age in the mouse forebrain. These declines in progenitor frequency and function correlate with increased expression of p16(INK4a), which encodes a cyclin-dependent kinase inhibitor linked to senescence(5). Ageing p16(INK4a)-deficient mice showed a significantly smaller decline in subventricular zone proliferation, olfactory bulb neurogenesis, and the frequency and self-renewal potential of multipotent progenitors. p16(INK4a) deficiency did not detectably affect progenitor function in the dentate gyrus or enteric nervous system, indicating regional differences in the response of neural progenitors to increased p16(INK4a) expression during ageing. Declining subventricular zone progenitor function and olfactory bulb neurogenesis during ageing are thus caused partly by increasing p16(INK4a) expression. ; Peer Reviewed ; http://deepblue.lib.umich.edu/bitstream/2027.42/62695/1/nature05091.pdfTest |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | 370291 bytes; 2489 bytes; application/pdf; text/plain |
| اللغة: | unknown |
| تدمد: | 0028-0836 |
| العلاقة: | Molofsky, Anna V.; Slutsky, Shalom G.; Joseph, Nancy M.; He, Shenghui; Pardal, Ricardo; Krishnamurthy, Janakiraman; Sharpless, Norman E.; Morrison, Sean J. (2006) "Increasing p16(INK4a) expression decreases forebrain progenitors and neurogenesis during ageing." Nature 443(7110): 448-452.; https://hdl.handle.net/2027.42/62695Test; http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=16957738&dopt=citationTest; http://dx.doi.org/10.1038/nature05091Test; Nature |
| DOI: | 10.1038/nature05091 |
| الإتاحة: | https://doi.org/10.1038/nature05091Test https://hdl.handle.net/2027.42/62695Test http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=16957738&dopt=citationTest |
| رقم الانضمام: | edsbas.5D23F78F |
| قاعدة البيانات: | BASE |
| تدمد: | 00280836 |
|---|---|
| DOI: | 10.1038/nature05091 |