Premature death and organ hypofunction after severe acute pancreatitis results from cellular senescence - mechanisms and new opportunities for therapy

细胞衰老导致重症急性胰腺炎后过早死亡和器官功能减退——机制和新的治疗机会

• 批准号: MR/P008887/1
• 负责人: Damian Mole
• 金额: $ 385.06万
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FP008887%2F1
• 关键词: Premature; death; organ; hypofunction; after

We have discovered that after a serious illness, for example one that needs treatment in intensive care, some people's vital organs do not work as well as they should. This negative effect can last for months and sometimes years afterwards. We have also discovered that people who have suffered a serious illness have a shorter life expectancy compared to others of a similar age, gender and overall general health. This happens even though these individuals appear to have made a complete recovery from their original illness. We believe that this is a serious problem for them and for society as a whole. Our goal is to help people to recover to their full potential after suffering a life-threatening illness.The idea behind our science is that serious illness results in premature ageing of vital organs within the body, for example the heart and lungs. Our idea is based on discoveries made over many years by us and other scientists. Whenever a cell divides in order for a person to grow or a vital organ to repair itself, for example the cells lining the bowel, liver cells and white blood cells of the immune system, that cell gets a little bit older. After a cell has divided a number of times, or if the DNA inside the cell gets damaged beyond repair, for example during a serious illness, that cell becomes aged. It is likely that these aged cells have stopped working properly. We think that inflammation during a serious illness leads to quicker and earlier aging of cells and that reduces a person's life expectancy.My area of expertise is looking after patients whose cells have become damaged during a serious illness called acute pancreatitis. Acute pancreatitis is inflammation in the pancreas - a vital organ that controls the digestion of food and blood sugar levels. Our research will be very helpful to people who have had pancreatitis and to those people who look after them. Added to that, we also think that our discoveries will be useful to other scientists and health professionals who study other serious illness, for example severe trauma or major surgery.Our research will use modern scientific techniques in the laboratory and build on what is already known in the scientific community. We are also going to invite patients who are recovering from pancreatitis to donate blood samples in order to measure damage in their cells, and do some medical tests over a period of time to see how their organs have aged as a result of pancreatitis, and to see how well they recover. When we have a better understanding of how cell damage and cell ageing are linked, we will be able to plan ways to improve a person's recovery after serious illness. We will share our discoveries with the scientific community, and work together to reach our goals.

我们发现，在患了严重疾病后，例如需要在重症监护病房接受治疗的疾病，一些人的重要器官没有发挥应有的作用。这种负面影响可能会持续数月，有时甚至会持续数年。我们还发现，与年龄、性别和总体健康状况相似的其他人相比，患有严重疾病的人的预期寿命更短。即使这些人似乎已经从最初的疾病中完全康复，这种情况也会发生。我们认为，这对他们和整个社会都是一个严重的问题。我们的目标是帮助人们在遭受危及生命的疾病后充分恢复他们的潜力。我们的科学背后的想法是，严重的疾病会导致体内重要器官过早老化，例如心脏和肺。我们的想法是基于我们和其他科学家多年来的发现。每当一个细胞分裂，以便一个人成长或一个重要的器官自我修复时，例如免疫系统的肠道细胞、肝细胞和白细胞，这个细胞就会变得有点老。在细胞分裂多次后，或者如果细胞内的DNA受损而无法修复，例如在严重疾病期间，该细胞就会衰老。这些老化的细胞很可能已经停止了正常工作。我们认为，严重疾病期间的炎症会导致细胞更快更早地老化，从而降低一个人的预期寿命。我的专业领域是照顾在一种名为急性胰腺炎的严重疾病中细胞受损的患者。急性胰腺炎是胰腺的炎症，胰腺是控制食物消化和血糖水平的重要器官。我们的研究将对患有胰腺炎的人和那些照顾他们的人非常有帮助。此外，我们还认为，我们的发现将对研究其他严重疾病的科学家和卫生专业人员有用，例如严重创伤或重大手术。我们的研究将在实验室使用现代科学技术，并建立在科学界已知的基础上。我们还将邀请正在从胰腺炎中恢复的患者捐献血液样本，以测量他们细胞的损害，并在一段时间内进行一些医学测试，看看他们的器官因胰腺炎而老化的情况，以及他们恢复得如何。当我们更好地了解细胞损伤和细胞老化是如何联系在一起的时候，我们将能够计划如何改善一个人在严重疾病后的恢复。我们将与科学界分享我们的发现，共同努力实现我们的目标。

项目成果

Kynurenine monooxygenase regulates inflammation during critical illness and recovery in experimental acute pancreatitis.

犬尿氨酸单加氧酶调节实验性急性胰腺炎危重疾病和恢复期间的炎症。

• DOI: 10.1016/j.celrep.2023.112763
• 发表时间: 2023
• 期刊: Cell reports
• 影响因子: 8.8
• 作者: Hayes AJ

Effects of dietary nitrate on respiratory physiology at high altitude - Results from the Xtreme Alps study.

• DOI: 10.1016/j.niox.2017.10.005
• 发表时间: 2017-12-01
• 期刊: Nitric oxide : biology and chemistry
• 作者: Cumpstey AF;Hennis PJ;Gilbert-Kawai ET;Fernandez BO;Poudevigne M;Cobb A;Meale P;Mitchell K;Moyses H;Pöhnl H;Mythen MG;Grocott MPW;Feelisch M;Martin DS;Xtreme Alps research group
• 通讯作者: Xtreme Alps research group

Shared activity patterns arising at genetic susceptibility loci reveal underlying genomic and cellular architecture of human disease.

• DOI: 10.1371/journal.pcbi.1005934
• 发表时间: 2018-03
• 期刊: PLoS computational biology
• 影响因子: 4.3
• 作者: Baillie JK;Bretherick A;Haley CS;Clohisey S;Gray A;Neyton LPA;Barrett J;Stahl EA;Tenesa A;Andersson R;Brown JB;Faulkner GJ;Lizio M;Schaefer U;Daub C;Itoh M;Kondo N;Lassmann T;Kawai J;IIBDGC Consortium;Mole D;Bajic VB;Heutink P;Rehli M;Kawaji H;Sandelin A;Suzuki H;Satsangi J;Wells CA;Hacohen N;Freeman TC;Hayashizaki Y;Carninci P;Forrest ARR;Hume DA
• 通讯作者: Hume DA

Kynurenine monooxygenase regulates inflammation during critical illness and recovery in experimental acute pancreatitis

犬尿氨酸单加氧酶调节实验性急性胰腺炎危重病和恢复期间的炎症

• DOI: 10.1016/j.hpb.2020.11.549
• 发表时间: 2021
• 期刊: HPB
• 影响因子: 2.9
• 作者: Hayes A

Benign liver lesions

良性肝脏病变

• DOI: 10.1016/j.mpsur.2017.09.009
• 发表时间: 2017
• 期刊: Surgery (Oxford)
• 作者: Hayes A