Determining the critical relationship between human epidermal lipids and microbiota in sustaining healthy skin ageing

医疗保健的改善和出生率的降低增加了英国和世界各地老年人的比例。随着我们年龄的增长，体内器官系统的功能会发生重大变化；需要研究来了解衰老的身体是如何适应以保持健康的。这种认识将有助于我们界定健康老龄化的定义，并将支持减少出现与年龄有关的健康问题的风险的努力。皮肤是保护身体免受环境影响的重要器官。皮肤的外层，称为表皮，形成一种屏障，调节体内水分和电解质的损失，并通过专业免疫细胞提供免疫屏障，这些细胞是人体抵御感染的一部分。皮肤表面覆盖着无数的微生物，统称为“微生物区系”。这些微生物对皮肤健康很重要，因为它们可以保护皮肤免受其他潜在致病微生物的伤害。微生物群还可以与免疫细胞相互作用，通过这种方式，增强皮肤保护自己免受感染的能力。随着年龄的增长，人类皮肤发生的自然变化降低了其维持这种屏障功能的能力；皮肤变得更薄、更脆弱，对感染的抵抗力更差，更容易形成溃疡和慢性伤口(即无法愈合的伤口)。在年轻皮肤中，这种表皮屏障的结构和功能取决于专门的皮肤脂类；随着年龄的增长，表皮的脂类含量会减少。皮肤微生物区系也随着年龄的增长而下降，无论是在皮肤上停留的微生物数量还是物种数量。有趣的是，皮肤脂质和微生物区系具有动态关系，其中脂类既是微生物的营养物质，也是微生物的控制因素，而微生物区系可以改变皮肤的脂肪环境。由于衰老同时影响表皮脂和微生物区系，我们相信，如果我们研究它们之间的关系，我们将在控制皮肤健康衰老的过程中获得重要的新信息。在这个项目中，我们提出了一种假设，即衰老会导致皮肤(称为脂质体)的脂肪含量发生变化，并且这些变化会影响皮肤驻留的微生物，从而导致老年人表皮屏障的功能降低。因此，在进行这个项目时，我们的目标是确定表皮脂质和皮肤微生物群之间的基线关系，这种关系在年轻人和老年人中有何不同，以及这些变化对老年人皮肤屏障的功能有什么影响。我们的研究有三个具体目标：1.随着人体年龄的增长，表皮的脂质成分和表皮屏障的功能是如何变化的？2.时间上的衰老对人体不同部位皮肤上发现的微生物区系的数量和类型有什么影响？3.表皮脂类和微生物区系之间有什么联系，这种关系是如何随着年龄的增长而变化的，以及带来与年龄相关的变化的事件序列是什么？通过完成这个项目，我们将首次能够展示皮肤脂类和微生物区系之间存在的确切关系的细节。以及它们在衰老过程中的关联是如何变化的。这些信息将提供对健康表皮屏障的自然状态的独特理解。此外，这一宝贵的见解将使我们能够设计干预措施，以防止使老化皮肤更容易患病的变化，并促进健康。这种干预措施有可能减轻个人健康不良的负担，并通过更长时间保持老年人皮肤的健康，对卫生保健系统产生积极的财务影响。

Improvements in health care and reductions in birth rates have increased the proportion of older people in the UK and worldwide. As we grow older, there are significant changes in how organ systems within the body function; research is needed to understand how an ageing body adapts to remain healthy. Such understanding will help us define healthy ageing and will support efforts to reduce the risk of developing age-related health problems. Skin is an important organ that protects the body from the environment. The outer layer of the skin, called the epidermis, forms a barrier that regulates the loss of water and electrolytes from the body, and provides an immunological barrier through specialist immune cells that are part of the body's defence against infections. The surface of the skin is covered by myriad microorganisms, collectively known as the 'microbiota'. These microorganisms are important for skin health as they can protect it from other potentially pathogenic microorganisms. The microbiota can also interact with immune cells and, in this way, strengthen the skin's ability to protect itself from infection. As we age the natural changes that occur in human skin reduce its ability to maintain this barrier function; skin becomes thinner and more fragile, less resistant to infections, and more susceptible to develop ulcers and chronic wounds (i.e. wounds that fail to heal). In young skin, the structure and function of this epidermal barrier is dependent upon specialist skin lipids; as ageing occurs, there is a reduction in the lipid content of the epidermis. Skin microbiota also decline with increasing age, both in terms of the number of microorganisms and the number of species resident on the skin. Interestingly, skin lipids and microbiota have a dynamic relationship where lipids act both as nutrients and control factors for the microorganisms, whilst the microbiota can change the skin's lipid environment. As ageing affects both epidermal lipids and microbiota, we believe that if we study their association we will gain important new information on the processes that control healthy skin ageing. In this project we propose to explore the hypothesis that ageing brings about changes in the lipid content of the skin (termed lipidome), and that these changes affect the skin-resident microorganisms, leading to reduced function of the epidermal barrier in the elderly. Therefore, in undertaking this project we aim to identify the baseline relationship between epidermal lipids and the skin microbiome, how this relationship is different in young and elderly individuals, and what effect these changes have on how the skin barrier functions in the elderly. Our research has three specific objectives: 1. How does the lipid composition of the epidermis and the function of the epidermal barrier change as the human body ages?2. What is the impact of chronological ageing on the number and type of microbiota that are found on the skin at different body sites?3. What is the association between the epidermal lipids and microbiota, how does this relationship change as we grow older, and what is the sequence of events that bring about the age-related changes?By completing this project we will be able to show for the first time the exact details of the relationship that exists between skin lipids and microbiota, and how their association changes during the process of ageing. This information will provide a unique understanding of the natural state of a healthy epidermal barrier. Furthermore, this valuable insight will give us the ability to design interventions to prevent changes that make aged skin more prone to ailments, and to promote health. Such interventions have the potential to ease the burden of ill health for the individuals, and also have a positive financial impact on health care systems by keeping older skin healthier for longer.