Geron Corporation, Menlo Park, California, USA.
Rejuvenation Res. 2011 Feb;14(1):45-56. doi: 10.1089/rej.2010.1085. Epub 2010 Sep 7.
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.
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。