MICA - DEfining MechanIsms Shared across mulTI-organ FIbrosis to prevent the development of long-term multi-morbidity DEMISTIFI-Multi Morbidity

修正后的报告摘要：内脏的瘢痕形成(“纤维化”)发生在许多常见疾病中，包括糖尿病(胰腺瘢痕形成)、高血压(血管)、慢性肾脏疾病(肾脏)、肝硬变(肝)和肺纤维化(肺)。内脏的疤痕可以阻止这些器官的正常工作，并导致全球约三分之一的死亡。人们可能会受到不止一个器官疤痕的影响。人们认为导致疤痕形成的因素包括吸烟、酒精、肥胖和新冠肺炎等感染。这些外部因素被称为“环境”因素。还有一些遗传因素(称为基因突变或变种)可以在受影响的人的家族中发生，这些人更有可能在更年轻的时候在不同的器官中留下疤痕。导致疤痕的遗传因素经常出现在短端粒综合症中，这是一种加速衰老的形式，会导致全身疤痕形成。在严重的情况下，这可能从童年开始，伤疤会影响到身体的不同部位。它通常从骨髓开始，导致严重的贫血、感染和出血，然后在肝脏导致硬化或肺导致死亡。其他人可能有他们可能不知道的较轻微的基因问题。这可能很常见，只有在老年或由吸烟、肥胖或饮酒过多等外部(环境)因素引发时才会造成疤痕。遗传和环境/外部风险因素很可能都会导致不同器官的疤痕形成，并可能在不同的时间发生。如果能够在年轻时识别出疤痕的模式，就可以防止在以后的生活中在多个器官中形成更广泛的疤痕。这可以通过识别有疤痕风险的人群，并找出哪些特定的治疗或药物对每个群体最有效来实现。在确定了这些人群后，将使用有针对性的疗法来鼓励人们改变他们的生活方式或服用对每个特定人最有可能有效的药物。我们研究的目的是确定不同器官的瘢痕形成模式，我们称之为纤维化多发性疾病(FMM)。我们将使用核磁共振成像(MRI)扫描等新技术来测量不同器官的疤痕程度，以便产生一个“纤维化多种疾病”评分(即，衡量疤痕的严重程度)。这将使我们能够确定疤痕的全部范围，提供早期警告，并检测疤痕从一个器官向另一个器官的扩散。我们将绘制不同器官中疤痕形成的遗传和环境/外部触发因素的图谱，并调查疤痕形成的潜在生物学原因，以便找到预防或治愈它的治疗方法。我们怀疑，许多已经在使用的药物可以帮助预防或治疗疤痕，但在我们推荐它们之前，我们需要证明这些药物有效。通过这种方式，我们希望向合适的人提供正确的治疗方法，防止疤痕破坏发现它的器官，并防止它扩散到其他器官。这些治疗可能涉及改变生活方式，如减肥和锻炼，和/或药物治疗。我们希望通过治疗和预防疤痕形成的纤维化，我们可能能够帮助许多人保持健康，活得更长、更健康。

Amended lay summary: Scarring ("fibrosis") of the internal organs occurs in many common diseases, including diabetes (scarring in the pancreas), high blood pressure (blood vessels), chronic kidney disease (kidney), cirrhosis (liver) and pulmonary fibrosis (lungs). Scarring of the internal organs can stop these organs working properly and causes about one third of all deaths world-wide. People can be affected by scarring in more than one organ.Factors believed to contribute to scarring include smoking, alcohol, obesity and infections such as COVID-19. These external factors are known as "environmental" factors. There are also a number of genetic factors (known as genetic mutations or 'variants') that can run in families with people affected more likely to have scarring in different organs, at a younger age.Genetic factors that cause scarring are often seen in short telomere syndrome, a form of accelerated aging, which leads to scarring throughout the body. In severe cases, this can start in childhood, with scarring affecting different parts of the body. It often starts with the bone marrow, causing severe anaemia, infections and bleeding, and later in the liver leading to cirrhosis or the lung leading to death. Other people could have milder genetic problems that they may not know about. These might be quite common and cause scarring only in old age or if triggered by external (environmental) factors such as smoking, obesity or drinking too much alcohol. It is likely that both genetic and environmental/external risk factors cause scarring of different organs and may happen at different times. If patterns of scarring can be identified when young, development of more extensive scarring, in multiple organs in later life, could be prevented. This could be done by identifying groups of people at risk of scarring and working out which specific treatments or medications will work best for each group. Having identified these groups of people, targeted therapies would be used to encourage people to change their lifestyle or to take the medicines that are most likely to be effective for each particular person. The aim of our research is to identify patterns of scarring in different organs, which we have termed Fibrotic Multi-Morbidity (FMM). We will use new technology such as Magnetic Resonance Imaging (MRI) scans to measure the extent of scarring in different organs, in order to generate a "Fibrotic Multi-Morbidity" Score (i.e., to measure the severity of the scarring). This will enable us to ascertain the full extent of scarring, provide an early warning and detect the spread of scarring from one organ to another. We will map the genetic and environmental/external triggers of scarring in different organs and investigate the underlying biological causes of the scarring so that we can find the treatments to prevent or cure it. We suspect that many medications that are already in use could help prevent or treat scarring but before we can recommend them, we need to prove that these medicines work.In this way, we hope to provide the right treatment to the right person to stop scarring from destroying the organ in which it is found and to prevent it spreading to other organs. These treatments could involve lifestyle changes, such as weight loss and exercise, and/or medications. We hope that by treating and preventing scarring- 'fibrosis', we may be able to help a lot of people stay healthy and live longer, healthier lives.