O21 Characterizing the impact of ageing/inflammageing on autophagy integrity in the skin

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ID: 318487
2026
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Abstract
Abstract Introduction and aims Epidermal and dermal homeostasis ensure the skin’s structural and functional integrity. Ageing deregulates this balance through extrinsic and intrinsic factors, promoting a low-grade chronic inflammatory profile (inflammaging), and an overall decline in the skin’s function. Autophagy – a process involving lysosomal degradation of autophagosome-packaged subcellular components – regulates skin homeostasis. However, the precise mechanisms by which ageing influences autophagic activity in the skin remains poorly understood. The present study aims to address this knowledge gap by elucidating the impact of ageing on autophagic function and exploring strategies to enhance autophagy to promote healthy skin ageing. Methods Proteomic approaches were employed to evaluate endogenous autophagy-related protein (ARP) expression across multiple skin compartments. Multiplex immunofluorescence analysis was performed on formalin-fixed paraffin-embedded skin tissues (n = 6) to assess spatial protein distribution. Western blot (WB) analysis was conducted on protein lysates derived from whole epidermal tissue (n = 9), and on lysates obtained from isolated human dermal fibroblasts (HDFs) (n = 11) to quantify ARP expression. Results Skin from younger donors exhibited a higher mean fluorescence intensity of lysosomal-associated membrane protein (LAMP)1 compared with skin from older donors. Further, younger donors showed widespread expression of ARPs throughout the epidermis, whereas older donors showed inconsistent patterns, with some samples displaying ARP expression restricted to suprabasal layers only. WB analysis of epidermal protein lysates corroborated these observations, revealing a relative decrease in LAMP1 and LAMP2 expression with age. Similarly, HDFs from older donors exhibited decreased LAMP1 levels, while conversely, an age-associated increase in the adaptor protein NDP52. Conclusions Older donor samples exhibited a decrease in lysosomal protein expression, alongside an increase of certain cargo receptors. These findings indicate that age-related autophagic flux decline may be linked to impaired lysosomal degradative function, underscoring the importance of targeting lysosomal pathways to restore homeostasis in skin ageing.
Reference Key
openalex_W7165651993 Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Kayumba Ng’andu, Jenny Pople, Ranjit Bhogal, Mike Philpott, Rosalind Hannen, Daniele Bergamaschi
Journal the british journal of dermatology
Year 2026
DOI
10.1093/bjd/ljag151.021
URL
https://doi.org/10.1093/bjd/ljag151.021
Keywords Keywords not found

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