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

全球和英国的预期寿命增加了，这带来了许多与健康有关的挑战，包括如何最好地支持和保持老年人的健康。衰老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，皮肤的功能会衰退；它变得更加脆弱，它的力量和弹性下降，当受到挑战时，它修复任何损害的能力也更弱。这些变化可能导致对感染和无法愈合的伤口的易感性增加，并且总体上可能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，表皮的结构发生了变化，我们观察到最外层的角质层发生了特殊的变化，角质层是保存水分的必要结构。这种“防水”层由专门的脂肪（称为脂质）组成，以提供正确的结构和功能。角质层内脂质与年龄相关的变化对表皮的特性有显著的影响。尽管与年龄相关的皮肤变化在男性和女性中都会发生，但人们对女性衰老的影响了解得更好，研究人员将其与更年期联系起来。我们相信，了解与年龄相关的皮肤变化何时在两性中发生，对于提供重要的新知识至关重要，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，帮助维持其健康功能。在这个项目中，我们将探索表皮脂质含量的基本变化，特别是角质层内的脂质含量的基本变化，可以随着年龄的增长影响皮肤的行为，在女性中，这是在更年期开始的。在这个项目中，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有关的分子机制。我们还想探索营养干预措施，随着年龄的增长，可以支持皮肤健康。我们的研究有三个主要目标：1。为了发现在健康的男性和女性中，我们在什么年龄开始看到皮肤功能（其强度和弹性）和表皮脂质组成的变化。2 .了解来自年轻人和老年人、男性和女性皮肤的表皮细胞（称为角化细胞）如何摄取和代谢维持角质层正确组成、结构和功能所需的脂质。探讨膳食补充多不饱和脂肪酸是否可以改善老年健康人皮肤的强度和弹性、其脂质组成及其修复表皮的能力。这项拟议中的研究将首次显示控制表皮功能随年龄增长而衰退的事件的时间顺序，同时，允许对同年龄的男性和女性的皮肤特性进行直接比较。此外，该研究将揭示老年角质形成细胞利用重要膳食脂质的能力的基本信息。通过使用简单的饮食干预，我们将发现脂质强化是否会导致角质层的形成，更好地抵御挑战和/或改善修复能力。获得衰老皮肤生物学中这些有价值的机制见解将为开发预防措施提供机会，并支持定制营养补充剂的开发，以满足衰老皮肤的特定需求，最终目标是在晚年保持皮肤健康。

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.