Torrance Jerry B, Goldband Steve
Physical Science Department, IBM Almaden Research Center, San Jose, CA 95120, USA.
Stanford Center on Longevity, Stanford University, Stanford, CA 94305, USA.
Int J Mol Sci. 2020 Oct 27;21(21):7959. doi: 10.3390/ijms21217959.
The last 20 years have seen a surge in scientific activity and promising results in the study of aging and longevity. Many researchers have focused on telomeres, which are composed of a series of TTAGGG repeat nucleotide sequences at the ends of each chromosome. Measurements of the length of these telomere strands show that they decrease in length with increasing age, leading many authors to propose that when the length of these telomere strands decreases sufficiently, the cells enter into a state of replicative senescence, eventually leading to disease and death. These ideas are supported by evidence that short telomere length is correlated with increased mortality. In this paper, we extend this idea to make an actual calculation of the predicted mortality rate caused by short telomere length induced senescence (STLIS). We derive a simple equation for the mathematical relationship between telomere length and mortality rate. Using only three parameters based on telomere length measurement data of Canadians, we have calculated both the magnitude and the age dependence of the mortality rate for both men and women. We show that these calculated data are in good quantitative agreement with the actual number of Canadians that die. This agreement demonstrates the quantitative correlation between the mortality calculated by the STLIS model and the mortality of the major diseases of aging (e.g., cardiovascular disease, many cancers and diabetes mellitus), which dominate human mortality. This result represents significant progress in our understanding of the factors behind the cause of aging.
在过去20年里,衰老与长寿研究领域的科学活动激增,成果斐然。许多研究人员聚焦于端粒,端粒由位于每条染色体末端的一系列TTAGGG重复核苷酸序列组成。对这些端粒链长度的测量表明,它们的长度会随着年龄增长而缩短,这使得许多作者提出,当这些端粒链的长度充分缩短时,细胞会进入复制性衰老状态,最终导致疾病和死亡。这些观点得到了证据支持,即端粒长度短与死亡率增加相关。在本文中,我们拓展了这一观点,对由短端粒长度诱导衰老(STLIS)导致的预测死亡率进行了实际计算。我们推导出了一个关于端粒长度与死亡率之间数学关系的简单方程。仅使用基于加拿大人端粒长度测量数据的三个参数,我们就计算出了男性和女性死亡率的大小及其年龄依赖性。我们表明,这些计算数据与加拿大实际死亡人数在数量上高度吻合。这种吻合证明了STLIS模型计算出的死亡率与主导人类死亡率的主要衰老相关疾病(如心血管疾病、多种癌症和糖尿病)的死亡率之间存在定量相关性。这一结果代表了我们在理解衰老成因背后因素方面取得的重大进展。