时光一天天地逝去，人们慢慢地变老，其中的过程对人类来说是个巨大的谜题。德国科学家近日鉴别出一组蛋白，能够揭示一个人的生物学年龄。这些生物标记可应用于医学之中，根据老年人的个体生物学年龄改进对他们的治疗。相关论文发表在美国《国家科学院院刊》（PNAS）上。
随着生活条件和医疗条件的日益改善，人类的寿命在不断延长。但是同时，很多老年人遭受着年龄相关性疾病的煎熬，而且由于实足年龄（chronological age）不一定与生物学年龄相符，医生们经常很难决定使用哪种治疗手段。
在最新的研究中，德国马普干细胞老化研究所的Lenhard Rudolph和同事仔细研究了端粒。端粒位于染色体末端，能保持染色体稳定，并起到保护作用。然而，细胞每次分裂，端粒都会缩短50至200个碱基对。在人体老化的过程中，端粒变得越来越短直至丧失了保护功能。结果，染色体变得不稳定，细胞丧失了分裂能力。科学家认为这就是细胞老化的原因之一。
Rudolph和同事发现，端粒的缩短和DNA损伤会在人类细胞中造成重叠反应。在这两种情况中，受影响的细胞会释放标记蛋白。Rudolph说：“令人感兴趣的是，同一种蛋白能在人类血液中检测到，而且其量的明显增加与衰老及年龄相关性疾病有关。”
这一研究结果不仅为生物学年龄提供了有意义的标记，同时也确证了人类衰老的DNA损伤假说。研究人员希望这些标记能在医疗中得到应用，这将使根据病患个体生物学年龄改进治疗成为可能，从而达到更好的效果。此外，Rudolph认为还有其它的应用。他说：“它们也可被用于测试行为干预、食品添加剂及药物治疗，以延缓老化过程。”（生物谷Bioon.com）
生物谷推荐原始出处：
PNAS，vol. 105 no. 32 11299-11304，Hong Jianga，K. Lenhard Rudolpha
Proteins induced by telomere dysfunction and DNA damage represent biomarkers of human aging and disease
Hong Jianga,b, Eric Schifferc, Zhangfa Songa, Jianwei Wanga, Petra Zürbigc, Kathrin Thedieckd, Suzette Moesd, Heike Bantele, Nadja Saale, Justyna Jantosc, Meiken Brechtf, Paul Jen?d, Michael N. Halld, Klaus Hagerf, Michael P. Mannse, Hartmut Heckerg, Arnold Ganserh, Konstanze D?hneri, Andrzej Bartkej, Christoph Meissnerk, Harald Mischakc, Zhenyu Jua,l, and K. Lenhard Rudolpha,m
Abstract
Telomere dysfunction limits the proliferative capacity of human cells by activation of DNA damage responses, inducing senescence or apoptosis. In humans, telomere shortening occurs in the vast majority of tissues during aging, and telomere shortening is accelerated in chronic diseases that increase the rate of cell turnover. Yet, the functional role of telomere dysfunction and DNA damage in human aging and diseases remains under debate. Here, we identified marker proteins (i.e., CRAMP, stathmin, EF-1α, and chitinase) that are secreted from telomere-dysfunctional bone-marrow cells of late generation telomerase knockout mice (G4mTerc−/−). The expression levels of these proteins increase in blood and in various tissues of aging G4mTerc−/− mice but not in aging mice with long telomere reserves. Orthologs of these proteins are up-regulated in late-passage presenescent human fibroblasts and in early passage human cells in response to γ-irradiation. The study shows that the expression level of these marker proteins increases in the blood plasma of aging humans and shows a further increase in geriatric patients with aging-associated diseases. Moreover, there was a significant increase in the expression of the biomarkers in the blood plasma of patients with chronic diseases that are associated with increased rates of cell turnover and telomere shortening, such as cirrhosis and myelodysplastic syndromes (MDS). Analysis of blinded test samples validated the effectiveness of the biomarkers to discriminate between young and old, and between disease groups (MDS, cirrhosis) and healthy controls. These results support the concept that telomere dysfunction and DNA damage are interconnected pathways that are activated during human aging and disease.
