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

端粒损耗率的遗传、环境和药理学决定因素：对预防与年龄相关的多发病的影响

• 批准号: MR/W028018/1
• 负责人: Timothy Powell
• 金额: $ 81.87万
• 依托单位: King's College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FW028018%2F1
• 关键词: Genetic; environmental; pharmacological; determinants; telomere

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.

英国国家统计局估计，在50年的时间内，将有860万人及65岁以上的人。更长的寿命具有明显的好处，但是当它与与年龄有关的疾病遭受的人口的比例增加有关时，它可能会给个别患者和经济带来负担。端粒是在我们年龄缩短的染色体结尾处的“ DNA尾巴”。假设端粒过早缩短对多种与年龄有关的疾病（包括冠状动脉疾病和类风湿关节炎）的易感性缩短。这是因为端粒长度非常短的细胞无法分裂和替代组织内的旧，受损或不健康的细胞。有趣的是，有证据表明，端粒缩短的速率可能会受到遗传，环境和药理因素的影响。对哪些特定因素影响端粒缩短率的更深入了解可能会使我们能够指出特定年龄相关疾病或与年龄相关疾病的群集的高风险，并确定预防或延迟发作的新方法。 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药物可能会减慢端粒缩短，并将其重新定义为抗衰老化合物。

项目成果

Limited evidence of a shared genetic relationship between C-reactive protein levels and cognitive function in older UK adults of European ancestry

欧洲血统的英国老年人的 C 反应蛋白水平与认知功能之间存在共同遗传关系的证据有限

• DOI: 10.3389/frdem.2023.1093223
• 发表时间: 2023
• 期刊: Frontiers in Dementia
• 作者: Packer A