Suppr超能文献

端粒复合物将如何进一步促进我们的长寿? - 端粒复合物的潜在新型生物标志物可对抗衰老和癌症。

How will telomeric complex be further contributed to our longevity? - the potential novel biomarkers of telomere complex counteracting both aging and cancer.

机构信息

Shanghai Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.

出版信息

Protein Cell. 2013 Aug;4(8):573-81. doi: 10.1007/s13238-013-3002-4. Epub 2013 Jul 18.

Abstract

With the smooth move towards the coming expected clinical reports of anticancer pharmaceutical molecules targeting telomeres and telomerase, and also with the exciting success in the extension of lifespan by regulating telomerase activity without increased onset of oncogenesis in laboratory mouse models (Garcia-Cao et al., 2006; Jaskelioff et al., 2011), we are convinced that targeting telomeres based on telomerase will be a potential approach to conquer both aging and cancer and the idea of longevity seems to be no more mysterious. More interestingly, emerging evidences from clinical research reveal that other telomeric factors, like specific telomeric binding proteins and nonspecific telomere associated proteins also show crucial importance in aging and oncogenesis. This stems from their roles in the stability of telomere structure and in the inhibition of DNA damage response at telomeres. Uncapping these proteins from chromosome ends leads to dramatic telomere loss and telomere dysfunction which is more abrupt than those induced by telomerase inactivation. Abnormal expression of these factors results in developmental failure, aging and even oncogenesis evidenced by several experimental models and clinical cases, indicating telomere specific proteins and its associated proteins have complimentary roles to telomerase in telomere protection and controlling cellular fate. Thus, these telomeric factors might be potential clinical biomarkers for early detection or even therapeutic targets of aging and cancer. Future studies to elucidate how these proteins function in telomere protection might benefit patients suffering aging or cancer who are not sensitive to telomerase mediation.

摘要

随着针对端粒和端粒酶的抗癌药物分子的临床报告预期即将公布,以及在实验室小鼠模型中通过调节端粒酶活性延长寿命而不增加致癌作用的令人兴奋的成功(Garcia-Cao 等人,2006 年;Jaskelioff 等人,2011 年),我们相信基于端粒酶的端粒靶向将是征服衰老和癌症的潜在方法,长寿的想法似乎不再神秘。更有趣的是,来自临床研究的新证据表明,其他端粒因子,如特定的端粒结合蛋白和非特异性端粒相关蛋白,在衰老和癌变中也具有重要作用。这源于它们在端粒结构稳定性和抑制端粒处的 DNA 损伤反应中的作用。从染色体末端解开这些蛋白的盖帽会导致端粒急剧丢失和端粒功能障碍,比端粒酶失活引起的更为突然。这些因素的异常表达导致发育失败、衰老甚至癌变,这在几个实验模型和临床病例中得到了证实,表明端粒特异性蛋白及其相关蛋白在端粒保护和控制细胞命运方面与端粒酶具有互补作用。因此,这些端粒因子可能是衰老和癌症早期检测甚至治疗靶点的潜在临床生物标志物。未来阐明这些蛋白在端粒保护中的作用的研究可能会使那些对端粒酶介导不敏感的患有衰老或癌症的患者受益。

相似文献

9
Treating Cancer by Targeting Telomeres and Telomerase.通过靶向端粒和端粒酶治疗癌症。
Antioxidants (Basel). 2017 Feb 19;6(1):15. doi: 10.3390/antiox6010015.

本文引用的文献

1
The role of telomeres in stem cells and cancer.端粒在干细胞和癌症中的作用。
Cell. 2013 Jan 31;152(3):390-3. doi: 10.1016/j.cell.2013.01.010.
2
Highly recurrent TERT promoter mutations in human melanoma.人类黑色素瘤中高度复发的 TERT 启动子突变。
Science. 2013 Feb 22;339(6122):957-9. doi: 10.1126/science.1229259. Epub 2013 Jan 24.
3
TERT promoter mutations in familial and sporadic melanoma.TERT 启动子突变与家族性和散发性黑色素瘤。
Science. 2013 Feb 22;339(6122):959-61. doi: 10.1126/science.1230062. Epub 2013 Jan 24.
8
Aging by telomere loss can be reversed.端粒损耗导致的衰老可以被逆转。
Cell Stem Cell. 2011 Jan 7;8(1):3-4. doi: 10.1016/j.stem.2010.12.013.

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验