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发现有效的端粒酶激活剂:开拓新的治疗和抗衰老视角。

Discovery of potent telomerase activators: Unfolding new therapeutic and anti-aging perspectives.

机构信息

Metabolomic Μedicine, Health Clinics for Autoimmune and Chronic Diseases, 10674 Athens, Greece.

Laboratory of Toxicology, Medical School, University of Crete, 71003 Heraklion, Greece.

出版信息

Mol Med Rep. 2019 Oct;20(4):3701-3708. doi: 10.3892/mmr.2019.10614. Epub 2019 Aug 23.

Abstract

Telomere length, a marker of cellular aging, decreases with age and it has been associated with aging‑related diseases. Environmental factors, including diet and lifestyle factors, affect the rate of telomere shortening which can be reversed by telomerase. Telomerase activation by natural molecules has been suggested to be an anti‑aging modulator that can play a role in the treatment of aging‑related diseases. This study aimed to investigate the effect of natural compounds on telomerase activity in human peripheral blood mononuclear cells (PBMCs). The tested compounds included Centella asiatica extract formulation (08AGTLF), Astragalus extract formulation (Nutrient 4), TA‑65 (containing Astragalus membranaceus extract), oleanolic acid (OA), maslinic acid (MA), and 3 multi‑nutrient formulas (Nutrients 1, 2 and 3) at various concentrations. The mean absorbance values of telomerase activity measured following treatment with some of the above‑mentioned formulations were statistically significantly higher compared to those of the untreated cells. In particular, in order of importance with respect to telomerase activation from highest to lowest, 08AGTLF, OA, Nutrient 4, TA‑65, MA, Nutrient 3 and Nutrient 2, triggered statistically significant increase in telomerase activity compared to the untreated cells. 08AGTLF reached the highest levels of telomerase activity reported to date, at least to our knowledge, increasing telomerase activity by 8.8 folds compared to untreated cells, while Nutrient 4 and OA were also potent activators (4.3‑fold and 5.9‑fold increase, respectively). On the whole, this study indicates that the synergistic effect of nutrients and natural compounds can activate telomerase and produce more potent formulations. Human clinical studies using these formulations are required to evaluate their mode of action. This would reveal the health benefits of telomerase activation through natural molecules and would shed new light onto the treatment of aging‑related diseases.

摘要

端粒长度是细胞衰老的标志物,随着年龄的增长而缩短,它与衰老相关疾病有关。环境因素,包括饮食和生活方式因素,会影响端粒缩短的速度,而端粒酶可以逆转这种速度。天然分子激活端粒酶被认为是一种抗衰老调节剂,可以在治疗与衰老相关的疾病中发挥作用。本研究旨在探讨天然化合物对人外周血单核细胞(PBMCs)中端粒酶活性的影响。测试的化合物包括积雪草提取物制剂(08AGTLF)、黄芪提取物制剂(Nutrient 4)、TA-65(含黄芪提取物)、齐墩果酸(OA)、熊果酸(MA)和 3 种多种营养素配方(Nutrients 1、2 和 3),浓度不同。与未处理细胞相比,用上述部分制剂处理后测量的端粒酶活性的平均吸光度值具有统计学显著升高。特别是,按对端粒酶激活的重要性从高到低排序,08AGTLF、OA、Nutrient 4、TA-65、MA、Nutrient 3 和 Nutrient 2 与未处理细胞相比,端粒酶活性均呈统计学显著增加。08AGTLF 达到了迄今为止报道的最高端粒酶活性水平,至少据我们所知,与未处理细胞相比,端粒酶活性增加了 8.8 倍,而 Nutrient 4 和 OA 也是有效的激活剂(分别增加了 4.3 倍和 5.9 倍)。总的来说,本研究表明,营养素和天然化合物的协同作用可以激活端粒酶并产生更有效的制剂。需要进行这些制剂的人体临床试验,以评估其作用模式。这将揭示通过天然分子激活端粒酶的健康益处,并为治疗与衰老相关的疾病提供新的思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c89a/6755196/188e5b8f5dda/MMR-20-04-3701-g00.jpg

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