Al-Dulaimi Sarah, Thomas Ross, Matta Sheila, Roberts Terry
Centre for Genome Engineering and Maintenance, Division of Biosciences, Department of Life Sciences, College of Health and Life Sciences, Brunel University London, Uxbridge, UB8 3PH, UK.
Respiratory Clinical Research Facility, Royal Brompton Hospital, Fulham Road, London, SW3 6HP, UK.
Biogerontology. 2025 Sep 4;26(5):178. doi: 10.1007/s10522-025-10315-x.
Epitalon, a naturally occurring tetrapeptide, is known for its anti-aging effects on mammalian cells. This happens through the induction of telomerase enzyme activity, resulting in the extension of telomere length. A strong link exists between telomere length and aging-related diseases. Therefore, telomeres are considered to be one of the biomarkers of aging, and increasing or maintaining telomere length may contribute to healthy aging and longevity. Epitalon has been the subject of several anti-aging studies however, quantitative data on the biomolecular pathway leading to telomere length increase, hTERT mRNA expression, telomerase enzyme activity, and ALT activation have not been extensively studied in different cell types. In this article, the breast cancer cell lines 21NT, BT474, and normal epithelial and fibroblast cells were treated with epitalon then DNA, RNA, and proteins were extracted. qPCR and Immunofluorescence analysis demonstrated dose-dependent telomere length extension in normal cells through hTERT and telomerase upregulation. In cancer cells, significant telomere length extension also occurred through ALT (Alternative Lengthening of Telomeres) activation. Only a minor increase in ALT activity was observed in Normal cells, thereby showing that it was specific to cancer cells. Our data suggests that epitalon can extend telomere length in normal healthy mammalian cells through the upregulation of hTERT mRNA expression and telomerase enzyme activity.
依普黄酮是一种天然存在的四肽,以其对哺乳动物细胞的抗衰老作用而闻名。这是通过诱导端粒酶活性来实现的,从而导致端粒长度的延长。端粒长度与衰老相关疾病之间存在紧密联系。因此,端粒被认为是衰老的生物标志物之一,增加或维持端粒长度可能有助于健康衰老和长寿。依普黄酮已成为多项抗衰老研究的对象,然而,关于导致端粒长度增加、hTERT mRNA表达、端粒酶活性和ALT激活的生物分子途径的定量数据,在不同细胞类型中尚未得到广泛研究。在本文中,用依普黄酮处理乳腺癌细胞系21NT、BT474以及正常上皮细胞和成纤维细胞,然后提取DNA、RNA和蛋白质。qPCR和免疫荧光分析表明,通过上调hTERT和端粒酶,正常细胞中端粒长度呈剂量依赖性延长。在癌细胞中,通过ALT(端粒替代延长)激活也发生了显著的端粒长度延长。在正常细胞中仅观察到ALT活性有轻微增加,从而表明它对癌细胞具有特异性。我们的数据表明,依普黄酮可以通过上调hTERT mRNA表达和端粒酶活性来延长正常健康哺乳动物细胞中的端粒长度。