Exploring interventions to maintain and prolong healthy skin function for an ageing population

全球和英国的预期寿命都增加了，这带来了许多与健康相关的挑战，包括如何最好地支持和维持老年人的健康。衰老会影响我们身体的每一个器官，包括我们的皮肤。随着年龄的增长，我们皮肤的功能会下降；它变得更加脆弱，它的强度和弹性会降低，当受到挑战时，它修复任何损伤的能力就会降低。这些变化会增加对感染和无法愈合的伤口的易感性，总体上会降低老年人的生活质量。表皮是我们皮肤的外层，是身体和环境之间的主要屏障。随着年龄的增长，表皮的结构会发生变化，我们观察到最外层的表皮--角质层--的特殊变化，角质层是保存水分所必需的结构。这种“防水”层由专门的脂肪(称为脂类)组成，这些脂肪被安排来提供正确的结构和功能。角质层内与年龄相关的脂质变化对表皮的性质有重大影响。尽管男性和女性都会发生与年龄相关的皮肤变化，但女性更好地理解了衰老的影响，在那里，人们已经将衰老与更年期联系起来进行了研究。我们相信，了解男女与年龄相关的皮肤变化对于提供重要的新知识是至关重要的，这将使我们能够提供指导和计划干预措施，以保护和加强老化的皮肤，帮助维持其健康的功能。在这个项目中，我们将探索一种假设，即表皮的脂肪含量的根本变化，特别是角质层内的脂肪含量，可以随着年龄的增长影响皮肤的行为，对于女性来说，这是在更年期开始的。通过这个项目，我们的目标是发现这些与年龄相关的变化何时开始在男性和女性中发生，并了解与年龄相关的皮肤功能下降所涉及的分子机制。我们还想探索随着年龄的增长能够支持皮肤健康的营养干预措施。我们的研究有三个关键目标：1.发现健康男性和女性在什么年龄开始看到皮肤功能(强度和弹性)以及表皮脂肪成分的变化。为了了解来自年轻人和老年人、男性和女性皮肤的表皮细胞(称为角质形成细胞)如何吸收和代谢维持角质层正确成分、结构和功能所需的脂类。探讨膳食补充多不饱和脂肪酸是否能改善老年健康受试者皮肤的强度和弹性、其脂质成分以及修复表皮的能力。这项拟议的研究将首次显示控制表皮功能随年龄增长而下降的事件的时间顺序，同时允许直接比较相同年龄的男性和女性之间的皮肤特性。此外，这项研究将揭示衰老角质形成细胞利用重要膳食脂肪的能力的基本信息。通过一个简单的饮食干预，我们将发现强化脂肪是否能够形成更坚固的角质层，更能抵御挑战和/或具有更好的修复能力。获得这些对老化皮肤生物学的有价值的机械见解将提供一个机会来制定预防措施，并支持开发定制的营养补充剂来满足老化皮肤的特定需求，最终目的是在以后的生活中保持皮肤健康。

Life expectancy globally and in the UK has increased and this brings many health-related challenges, including how best to support and maintain health in older people. Ageing affects every organ in our body, including our skin. As we age, the function of our skin declines; it becomes more fragile, its strength and resilience are reduced and, when challenged, it is less able to repair any damage. These changes can lead to increased susceptibility to infections and wounds that fail to heal, and, overall, can reduce the quality of life of older people.The epidermis is the outer layer of our skin and is the major barrier between the body and the environment. With increasing age, the structure of the epidermis alters and we observe specific changes to the outermost epidermal layer, the stratum corneum, the structure essential to conserve water. This 'waterproof' layer consists of specialist fats (called lipids) arranged to provide its correct structure and function. Age-related changes to lipids within the stratum corneum have a significant impact upon the properties of the epidermis. Although age-related skin changes occur in both men and women, the impact of ageing is understood better in women, where it has been studied in association with the menopause. We believe that understanding when age-related skin changes occur in both genders is essential to provide important new knowledge, which will allow us to provide guidance and plan interventions to protect and strengthen the aged skin, helping to maintain its healthy function.In this project we will explore the hypothesis that fundamental changes in the lipid content of the epidermis, particularly within the stratum corneum, can influence the behaviour of the skin with increasing age and, in females, this is initiated at menopause. In undertaking this project, we aim to discover when these age-related changes start to occur in both men and women, and to understand the molecular mechanisms that are involved in the age-related decline of skin function. We also want to explore nutritional interventions that can support skin health as we age. Our research has three key objectives:1. To discover at what age we begin to see changes in how skin functions (its strength and resilience) and in the lipid composition of the epidermis, in healthy men and women.2. To understand how epidermal cells, called keratinocytes, from the skin of young and old, men and women, can uptake and metabolise lipids needed to maintain the correct composition, structure and function of the stratum corneum.3. To explore whether dietary supplementation with polyunsaturated fatty acids can improve skin's strength and resilience, its lipid composition, and its ability to repair the epidermis in older healthy human subjects. The proposed research will show for the first time the chronological sequence of events that control the decline of epidermal function with increased age, and, at the same time, allow a direct comparison of skin properties between men and women of the same age. Furthermore, the research will reveal fundamental information on the ability of aged keratinocytes to use important dietary lipids. By using a simple dietary intervention, we will discover whether lipid fortification results in the formation of a stronger stratum corneum, better able to withstand challenges and/or have improved capacity for repair. Obtaining these valuable mechanistic insights into the biology of aged skin will provide an opportunity to develop preventative measures, and support the development of bespoke nutritional supplements to address the specific needs of aged skin, with ultimate aim of maintaining skin health in later life.