Ait-Ghezala Ghania, Hassan Samira, Tweed Miles, Paris Daniel, Crynen Gogce, Zakirova Zuchra, Crynen Stefan, Crawford Fiona
Altern Ther Health Med. 2016 Jun;22 Suppl 2:6-14.
Context • Telomeres are repeated deoxyribonucleic acid (DNA) sequences (TTAGGG) that are located on the 5' ends of chromosomes, and they control the life span of eukaryotic cells. Compelling evidence has shown that the length of a person's life is dictated by the limited number of times that a human cell can divide. The enzyme telomerase has been shown to bind to and extend the length of telomeres. Thus, strategies for activating telomerase may help maintain telomere length and, thus, may lead to improved health during aging. Objective • The current study intended to investigate the effects of several natural compounds on telomerase activity in an established cell model of telomere shortening (ie, IMR90 cells). Design • The research team designed an in vitro study. Setting • The study was conducted at Roskamp Institute in Sarasota, FL, USA. Intervention • The tested single compounds were (1) α-lipoic acid, (1) green tea extract, (2) dimethylaminoethanol L-bitartrate (DMAE L-bitartrate), (3) N-acetyl-L-cysteine hydrochloride (HCL), (4) chlorella powder, (5) L-carnosine, (6) vitamin D3, (7) rhodiola PE 3%/1%, (8) glycine, (9) French red wine extract, (10) chia seed extract, (11) broccoli seed extract, and (12) Astragalus (TA-65). The compounds were tested singly and as blends. Outcome Measures • Telomerase activity for single compounds and blends of compounds was measured by the TeloTAGGG telomerase polymerase chain reaction (PCR) enzyme-linked immunosorbent assay (ELISA). The 4 most potent blends were investigated for their effects on cancer-cell proliferation and for their potential effects on the cytotoxicity and antiproliferative activity of a chemotherapeutic agent, the topoisomerase I inhibitor topotecan. The benefits of 6 population doublings (PDs) were measured for the single compounds, and the 4 blends were compared to 3 concentrations of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Results • Certain of the compounds increased telomerase activity, and combinations of the top-ranking compounds were able to increase telomerase activity significantly, from 51% to 290%, relative to controls. Conclusions • The results have confirmed that many naturally occurring compounds hold the potential to activate telomerase and that certain of those compounds have demonstrated synergistic effects to produce more potent blends. Given the relationship between telomere shortening, aging, and the decline of tissue function, it is reasonable to hypothesize that such telomerase-activating blends may have health-promoting benefits, particularly in relation to aging-associated conditions. Further investigation of such blends in human studies that are designed to evaluate safety and the effects on telomere length are thus warranted.
背景 • 端粒是位于染色体5'端的重复脱氧核糖核酸（DNA）序列（TTAGGG），它们控制着真核细胞的寿命。有力证据表明，人的寿命长短由人类细胞可分裂的有限次数决定。已证实端粒酶可结合并延长端粒长度。因此，激活端粒酶的策略可能有助于维持端粒长度，进而在衰老过程中改善健康状况。
目的 • 本研究旨在调查几种天然化合物对已建立的端粒缩短细胞模型（即IMR90细胞）中端粒酶活性的影响。
设计 • 研究团队设计了一项体外研究。
地点 • 该研究在美国佛罗里达州萨拉索塔的罗斯坎普研究所进行。
干预 • 所测试的单一化合物有：（1）α-硫辛酸，（1）绿茶提取物，（2）L-酒石酸二甲氨基乙醇酯（DMAE L-酒石酸盐），（3）盐酸N-乙酰-L-半胱氨酸（HCL），（4）小球藻粉，（5）L-肌肽，（6）维生素D3，（7）3%/1%的红景天提取物，（8）甘氨酸，（9）法国红酒提取物，（10）奇亚籽提取物，（11）西兰花籽提取物，以及（12）黄芪（TA-65）。这些化合物单独及混合进行测试。
观察指标 • 通过TeloTAGGG端粒酶聚合酶链反应（PCR）酶联免疫吸附测定（ELISA）测量单一化合物及化合物混合物的端粒酶活性。对4种最有效的混合物进行研究，观察它们对癌细胞增殖及对化疗药物拓扑异构酶I抑制剂拓扑替康的细胞毒性和抗增殖活性的潜在影响。测量单一化合物6次群体倍增（PDs）的益处，并将4种混合物与3种浓度的二十碳五烯酸（EPA）和二十二碳六烯酸（DHA）进行比较。
结果 • 某些化合物可增加端粒酶活性，排名靠前的化合物组合能够显著提高端粒酶活性，相对于对照组提高了51%至290%。
结论 • 结果证实，许多天然存在的化合物具有激活端粒酶的潜力，其中某些化合物已显示出协同作用，可产生更有效的混合物。鉴于端粒缩短、衰老与组织功能衰退之间的关系，合理推测此类激活端粒酶的混合物可能具有促进健康的益处，尤其是与衰老相关的状况。因此，有必要在旨在评估安全性及对端粒长度影响的人体研究中进一步研究此类混合物。
