The Impact of inflammaging on Epidermal Autophagy

Abstract

The skin is an important organ that provides the body with protection, structure, hydration, and maintaining homeostasis. One of the key regulatory processes in maintaining skin homeostasis is autophagy. Autophagy is characterised by the degradation and recycling process of unused intracellular cellular components by the cellular components called autolysosome, formed from phagophores and lysosomes. This balanced mechanism is essential to maintain skin and other tissues’ structures and functions. One of the changes that skin naturally undergoes is inflammaging, which is the altered skin phenotype that is similar to inflamed skin in accordance to ageing. Based on the previous studies indicating that autophagy is inhibited in cases of inflammation. In this thesis, we hypothesised the association of inflammaging with the autophagic mechanism within the epidermal skin. Using isolated skin fibroblast, isolated skin keratinocytes, and human skin biopsies obtained from young and old donors. Autophagy markers, including phagophore proteins, p62 and microtubule-associated protein 1A/1B-light chain 3 (LC3II); lysosomal membrane markers, Lysosomal associated membrane protein 1 (LAMP 1), LAMP 2, and LAMP 3; and lysosomal protease enzymes, cathepsin-B, cathepsin-D, and cathepsin-H); were investigated. The expression of these proteins in the old and young skins was varied through the cell types and age groups. Results highlighting the significant increase of LC3 marker in old keratinocytes, while presenting a remarkable decline in LAMP 2 and LAMP 3 expression in older fibroblasts and keratinocytes, respectively. Immunostained images of skin biopsies showed a significantly lower expression of LC3 in aged epidermis compared to younger skin. Overall, these findings suggest the importance of addressing the possible impact of other factors accompanying ageing, which are needed to be investigated in the future to better understand the alterations in autophagy mechanisms with respect to inflammaging.