The telomerase activator TA-65 elongates short telomeres and increases health span of adult/old mice without increasing cancer incidence.
The telomerase activator TA-65 elongates short telomeres and increases health span of adult/old mice without increasing cancer incidence.
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DOI：
10.1111/j.1474-9726.2011.00700.x
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发表时间：
2011-08
期刊：
影响因子：
7.8
通讯作者：
Blasco MA
中科院分区：
文献类型：
--
作者：
Bernardes de Jesus B;Schneeberger K;Vera E;Tejera A;Harley CB;Blasco MA
在这里，我们发现从黄芪根中纯化的端粒酶小分子激活剂（TA-65）能够增加端粒平均长度，降低含有端粒极短和端粒酶RNA Terc基因单拷贝（G3 Terc+/−mef）的单倍不足小鼠胚胎成纤维细胞（mef）的临界短端粒百分比和DNA损伤。重要的是，TA-65不会导致端粒延长或修复类似处理的端粒酶缺陷G3 Terc - / -同体mef的DNA损伤。这些结果表明，TA-65治疗导致端粒酶依赖的短端粒延长和相关DNA损伤的修复，从而证明TA-65的作用机制是通过端粒酶途径。此外，我们证明，当TA-65作为小鼠标准饮食的一部分补充时，TA-65能够增加某些小鼠组织中的mTERT水平，并延长极短的端粒。最后，在雌性小鼠中补充TA-65可以改善某些健康指标，包括葡萄糖耐量、骨质疏松症和皮肤健康，而不会显著增加全球癌症发病率。
Here, we show that a small-molecule activator of telomerase (TA-65) purified from the root of Astragalus membranaceus is capable of increasing average telomere length and decreasing the percentage of critically short telomeres and of DNA damage in haploinsufficient mouse embryonic fibroblasts (MEFs) that harbor critically short telomeres and a single copy of the telomerase RNA Terc gene (G3 Terc+/− MEFs). Importantly, TA-65 does not cause telomere elongation or rescues DNA damage in similarly treated telomerase-deficient G3 Terc−/− littermate MEFs. These results indicate that TA-65 treatment results in telomerase-dependent elongation of short telomeres and rescue of associated DNA damage, thus demonstrating that TA-65 mechanism of action is through the telomerase pathway. In addition, we demonstrate that TA-65 is capable of increasing mTERT levels in some mouse tissues and elongating critically short telomeres when supplemented as part of a standard diet in mice. Finally, TA-65 dietary supplementation in female mice leads to an improvement of certain health-span indicators including glucose tolerance, osteoporosis and skin fitness, without significantly increasing global cancer incidence.
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影响因子：
5.3
作者：
Canela, A;Martín-Caballero, J;Blasco, MA
通讯作者：
Blasco, MA
DOI：
10.1056/nejmra0903373
发表时间：
2009-12-10
期刊：
The New England journal of medicine
影响因子：
--
作者：
Calado RT;Young NS
通讯作者：
Young NS
影响因子：
5.8
作者：
Blueher, Matthias;Bashan, Nava;Rudich, Assaf
通讯作者：
Rudich, Assaf
影响因子：
56.9
作者：
Flores, I;Cayuela, ML;Blasco, MA
通讯作者：
Blasco, MA
影响因子：
64.8
作者：
Chang, LF;Karin, M
通讯作者：
Karin, M