Genetic, environmental, and pharmacological determinants of telomere attrition rates: Implications for the prevention of age-related multimorbidity

英国国家统计局估计，在50年的时间里，65岁及以上的人口将增加860万。较长的寿命有明显的好处，但当它与患有与年龄有关的疾病的人口比例增加相关联时，它可能对个人患者和经济造成负担。端粒是染色体末端的“DNA尾巴”，随着年龄的增长而缩短。端粒过早缩短被假设为易患多种年龄相关疾病，包括冠状动脉疾病和类风湿性关节炎。这是因为端粒长度非常短的细胞不太能够分裂和替换组织中的旧的，受损的或不健康的细胞。有趣的是，有证据表明端粒缩短的速率可能受到遗传，环境和药理学因素的影响。更深入地了解哪些特定因素会影响端粒缩短的速率，可能使我们能够确定特定年龄相关疾病或年龄相关疾病集群的高风险个体，并确定预防或延迟其发病的新方法。在这笔赠款中，我将利用英国50万成年人的端粒长度数据来确定：（a）哪些遗传因素影响我们端粒缩短的速度，（B）端粒缩短的速度如何影响不同类型疾病的风险，（c）特定的环境或生活方式因素（d）现有药物是否可能减缓端粒缩短并被重新用作抗衰老化合物。

The UK Office for National Statistics estimates that in 50 years' time, there will be an additional 8.6 million people aged 65 years and over. Longer lifespan has clear benefits, but when it is associated with an increased proportion of the population suffering from age-related diseases, it can pose a burden to individual sufferers and to the economy. Telomeres are 'DNA tails' at the end of chromosomes that shorten as we age. Premature telomere shortening is hypothesized to predispose individuals to multiple age-related diseases, including coronary artery disease and rheumatoid arthritis. This is because cells with very short telomere lengths are less able to divide and replace old, damaged or unhealthy cells within tissues. Interestingly, there is evidence that the rate of telomere shortening can be affected by genetic, environmental and pharmacological factors. A deeper understanding of which specific factors affect rates of telomere shortening might allow us to pinpoint individuals at high risk of specific age-related diseases or clusters of age-related diseases, and identify new ways of preventing or delaying their onset. Within this grant, I will make use of telomere length data generated from half a million adults in the UK, to determine: (a) which genetic factors affect the rate at which our telomeres shorten, (b) how faster telomere shortening impacts on risk for different types of diseases, (c) whether specific environmental or lifestyle factors (e.g. exercise, diet) can protect from faster telomere shortening and diseases in late adulthood, (d) whether existing drugs might slow telomere shortening and be repurposed as anti-ageing compounds.