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Integrated analysis of the impact of age-associated neuronal and enteroendocrine changes on normal bowel functions

年龄相关神经元和肠内分泌变化对正常肠道功能影响的综合分析

基本信息

批准号：
BB/G015147/1
负责人：
Mark Yeoman
金额：
$ 35.88万
依托单位：
University of Brighton
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2009
资助国家：
英国
起止时间：
2009 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FG015147%2F1
关键词：
Integrated analysis impact age associated

项目摘要

In the ageing population, terminal bowel dysfunction, manifest as faecal incontinence, which is often linked with faecal impaction, is very common and a significant cause of morbidity. Normal bowel function and defecation depend upon involuntary actions of the terminal colon, rectum and internal anal sphincter, and voluntary control of the external anal sphincter and pelvic floor muscles. These processes, in turn, depend upon the structural integrity and the normal molecular and physiological properties of the complex system of nerves, muscles and secretory cells that together make up this part of the digestive tract. Many cells and tissues are known to undergo structural and molecular changes during ageing that result in changes to their functional properties. Little is known however, of the changes that occur in the cells of the terminal bowel during ageing. The aim of the proposed project is therefore to use a multi-disciplinary approach, bringing together expertise from four academics, to fully characterise the physiological, molecular and structural age-associated changes in the cells of the terminal colon, rectum and anal sphincters. The work will be performed in mice, for a number of reasons; mice have a life-span amenable to studies on ageing; many of the variables associated with studies on humans can be avoided; mouse gastrointestinal physiology is well-understood and readily analysed and in future, research based on the data obtained from this project will be able to employ the powerful tool of mouse genetics to further analyse the changes that occur in ageing terminal bowel. The results of this work will allow more effective therapies for the treatment of age-associated incontinence and faecal impaction to be developed

在老龄化人群中，末期肠功能障碍（表现为大便失禁，通常与粪便嵌塞有关）非常常见，也是发病的重要原因。正常的肠道功能和排便取决于末端结肠、直肠和肛门内括约肌的不自主活动，以及肛门外括约肌和盆底肌肉的自主控制。这些过程反过来又取决于共同构成消化道这一部分的神经、肌肉和分泌细胞复杂系统的结构完整性以及正常的分子和生理特性。众所周知，许多细胞和组织在衰老过程中会经历结构和分子变化，从而导致其功能特性发生变化。然而，人们对衰老过程中末端肠细胞发生的变化知之甚少。因此，该项目的目的是采用多学科方法，汇集四位学者的专业知识，全面表征末端结肠、直肠和肛门括约肌细胞中与年龄相关的生理、分子和结构变化。出于多种原因，这项工作将在小鼠身上进行；小鼠的寿命适合衰老研究；许多与人类研究相关的变量是可以避免的；小鼠胃肠道生理学已被充分理解并易于分析，未来基于该项目获得的数据的研究将能够利用小鼠遗传学这一强大工具来进一步分析衰老末期肠道中发生的变化。这项工作的结果将有助于开发出更有效的疗法来治疗与年龄相关的尿失禁和粪便嵌塞