Hyaluronan and proteoglycan link protein 1 - A novel signaling molecule for rejuvenating aged skin.
Abstract
The skin seems to rejuvenate upon exposure to factors within the circulation of young organisms. Intrinsic factors that modulate skin aging are poorly understood. We used heterochronic parabiosis and aptamer-based proteomics to identify serum-derived rejuvenating factors. We discovered a novel extracellular function of hyaluronan and proteoglycan link protein 1 (HAPLN1). Its serum levels decreased with age, disturbing the integrity of the skin extracellular matrix, which is predominantly composed of collagen I and hyaluronan; levels of various markers, which decrease in aged skin, were significantly restored in vivo and in vitro by the administration of recombinant human HAPLN1 (rhHAPLN1). rhHAPLN1 protected transforming growth factor beta receptor 2 on the cell surface from endocytic degradation via mechanisms such as regulation of viscoelasticity, CD44 clustering. Moreover, rhHAPLN1 regulated the levels of nuclear factor erythroid 2-related factor 2, phosphorylated nuclear factor kappa B, and some cyclin-dependent kinase inhibitors such as p16 and p21. Therefore, rhHAPLN1 may act as a novel biomechanical signaling protein to rejuvenate aged skin.
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Research summary
The paper investigates a novel signaling molecule, HAPLN1, that appears to play a role in rejuvenating aged skin by restoring extracellular matrix integrity and modulating cellular signaling pathways associated with aging. This focus on a potential mechanism for reversing aspects of skin aging aligns with longevity research. However, while the findings are interesting and contribute to the understanding of skin aging, they represent a solid but limited advance in the broader context of aging research, thus warranting a score of 4.
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