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

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.

Ageing impacts skin function and quality; it becomes fragile, has reduced biomechanical capacity and an impaired ability to repair damage. Changes to stratum corneum (SC) lipids in the outer epidermis contribute to age-related physiological decline. Whilst more data is available in aged female skin, due to studies in menopausal volunteers, little is known about the temporal dynamics of tissue failure. The proposed research aims to discover the timing of age-related changes in both genders, understand the molecular mechanism of epidermal decline, and explore interventions to support aged skin health.
Our objectives are to: 1) discover at what age biomechanical function and epidermal lipid composition alter in males and females; 2) understand how epidermal keratinocytes (young and old; male and female) metabolise polyunsaturated fatty acids (PUFAs) important for SC function; 3) explore the impact of PUFA interventions on the epidermal lipidome, biomechanical and physiological function in aged subjects.
Using a cohort human study, we will identify cutaneous changes as a function of age in men and women, using non-invasive biomechanical (cutometry) and physiological (capacitance, trans-epidermal water loss) measures, mass spectrometry lipidomics and gene expression studies. A 3D in vitro model of epidermal keratinocytes will provide mechanistic insight into the impact of PUFA on ceramides and related enzymes, fatty acid receptors and transfer proteins, and SC biophysical properties. An interventional feasibility study in post-menopausal female volunteers will assess whether PUFA supplements positively impact the SC lipidome, epidermal biomechanics, physiological function, and ability to repair following a challenge. The project will identify for the first time the timing of age-dependent epidermal decline, provide fundamental insight into the underpinning mechanistic drivers, and assess the feasibility of dietary interventions to maintain skin health in later life.