Boccardi Virginia, Cari Luigi, Bastiani Patrizia, Scamosci Michela, Cecchetti Roberta, Nocentini Giuseppe, Mecocci Patrizia
Division of Gerontology and Geriatrics, Department of Medicine and Surgery, University of Perugia, Santa Maria Della Misericordia Hospital, Perugia, Italy.
Department of Medicine and Surgery, Institute of Gerontology and Geriatrics, University of Perugia, Piazzale Gambuli 1, 06132, Perugia, Italy.
Biogerontology. 2024 Nov;25(6):1069-1077. doi: 10.1007/s10522-024-10120-y. Epub 2024 Jul 13.
Telomeres undergo a progressive shortening process as individuals age, and it has been proposed that severely shortened and dysfunctional telomeres play a role in the aging process and the onset of age-related diseases in human beings. An emerging body of evidence indicates that the shortening of telomeres in cultured human cells is also influenced by other replication defects occurring within telomeric repeats. These abnormalities can be detected on metaphase chromosomes. Recent studies have also identified a set of serological markers for telomere dysfunction and DNA damage (elongation factor 1α [EF-1α], stathmin, and N-acetyl-glucosaminidase). With this study, the correlation between telomere abnormalities (by FISH) and these biomarkers as measured in blood serum (by ELISA) from a cohort of 22 healthy subjects at different ages (range 26-101 years) was analyzed. A strong positive correlation between aging and the presence of aberrant telomere structures, sister telomere loss (STL), and sister telomere chromatid fusions (STCF) was detected. When serum markers of telomere dysfunction were correlated with telomere abnormalities, we found that stathmin correlated with total aberrant telomeres structures (r = 0.431, p = 0.0453) and STCF (r = 0.533, p = 0.0107). These findings suggest that serum stathmin can be considered an easy-to-get marker of telomere dysfunction and may serve as valuable indicators of aging.
随着个体年龄增长，端粒会经历一个逐渐缩短的过程，并且有人提出，严重缩短且功能失调的端粒在人类衰老过程及与年龄相关疾病的发病中起作用。越来越多的证据表明，培养的人类细胞中端粒的缩短也受到端粒重复序列内发生的其他复制缺陷的影响。这些异常可在中期染色体上检测到。最近的研究还确定了一组端粒功能障碍和DNA损伤的血清学标志物（延伸因子1α [EF-1α]、微管相关蛋白2和N-乙酰葡糖胺酶）。在这项研究中，分析了来自22名不同年龄（范围为26 - 101岁）健康受试者队列的血液血清（通过ELISA法）中通过荧光原位杂交（FISH）检测的端粒异常与这些生物标志物之间的相关性。检测到衰老与异常端粒结构、姐妹端粒丢失（STL）和姐妹端粒染色单体融合（STCF）的存在之间存在强正相关。当端粒功能障碍的血清标志物与端粒异常相关时，我们发现微管相关蛋白2与总异常端粒结构（r = 0.431，p = 0.0453）和STCF（r = 0.533，p = 0.0107）相关。这些发现表明，血清微管相关蛋白2可被视为端粒功能障碍的一个易于获取的标志物，并且可能作为衰老的有价值指标。
