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天然产物端粒酶激活剂作为健康维护计划的一部分。

A natural product telomerase activator as part of a health maintenance program.

机构信息

Geron Corporation, Menlo Park, California, USA.

出版信息

Rejuvenation Res. 2011 Feb;14(1):45-56. doi: 10.1089/rej.2010.1085. Epub 2010 Sep 7.

Abstract

Most human cells lack sufficient telomerase to maintain telomeres, hence these genetic elements shorten with time and stress, contributing to aging and disease. In January, 2007, a commercial health maintenance program, PattonProtocol-1, was launched that included a natural product-derived telomerase activator (TA-65®, 10-50 mg daily), a comprehensive dietary supplement pack, and physician counseling/laboratory tests at baseline and every 3-6 months thereafter. We report here analysis of the first year of data focusing on the immune system. Low nanomolar levels of TA-65® moderately activated telomerase in human keratinocytes, fibroblasts, and immune cells in culture; similar plasma levels of TA-65® were achieved in pilot human pharmacokinetic studies with single 10- to 50-mg doses. The most striking in vivo effects were declines in the percent senescent cytotoxic (CD8(+)/CD28(-)) T cells (1.5, 4.4, 8.6, and 7.5% at 3, 6, 9, and 12 months, respectively; p = not significant [N.S.], 0.018, 0.0024, 0.0062) and natural killer cells at 6 and 12 months (p = 0.028 and 0.00013, respectively). Most of these decreases were seen in cytomegalovirus (CMV) seropositive subjects. In a subset of subjects, the distribution of telomere lengths in leukocytes at baseline and 12 months was measured. Although mean telomere length did not increase, there was a significant reduction in the percent short (<4 kbp) telomeres (p = 0.037). No adverse events were attributed to PattonProtocol-1. We conclude that the protocol lengthens critically short telomeres and remodels the relative proportions of circulating leukocytes of CMV(+) subjects toward the more "youthful" profile of CMV(-) subjects. Controlled randomized trials are planned to assess TA-65®-specific effects in humans.

摘要

大多数人类细胞缺乏足够的端粒酶来维持端粒,因此这些遗传元件会随着时间和压力的增加而缩短,导致衰老和疾病。2007 年 1 月,启动了一项商业健康维护计划 PattonProtocol-1,其中包括一种天然产物衍生的端粒酶激活剂(TA-65®,每天 10-50 毫克)、综合膳食补充剂包以及基线和此后每 3-6 个月进行一次的医生咨询/实验室测试。我们在此报告第一年的数据分析,重点是免疫系统。低纳摩尔水平的 TA-65®可适度激活培养中的人类角质形成细胞、成纤维细胞和免疫细胞中的端粒酶;在单次 10-50 毫克剂量的人体药代动力学研究中,达到了类似的血浆 TA-65®水平。最引人注目的体内效应是衰老细胞毒性(CD8(+)/CD28(-))T 细胞的百分比下降(分别在第 3、6、9 和 12 个月时为 1.5%、4.4%、8.6%和 7.5%;p 值无显著差异 [N.S.],0.018、0.0024 和 0.0062)和第 6 和 12 个月的自然杀伤细胞(p 值分别为 0.028 和 0.00013)。这些下降大多发生在巨细胞病毒(CMV)血清阳性受试者中。在一组受试者中,测量了白细胞在基线和 12 个月时的端粒长度分布。尽管平均端粒长度没有增加,但短端粒(<4 kbp)的百分比明显减少(p=0.037)。没有与 PattonProtocol-1 相关的不良事件。我们得出的结论是,该方案可延长严重缩短的端粒,并重塑 CMV(+)受试者循环白细胞的相对比例,使其更接近 CMV(-)受试者的“年轻”特征。计划进行对照随机试验,以评估 TA-65®在人类中的特异性作用。

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