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Following treatment with HSA, collagen type I and type III was assessed in primary human dermal fibroblasts together with collagen type III, p53 protein levels and sunburn cells (SBC) after UVB irradiation (1\u00a0J\u00a0cm<jats:sup>\u22122<\/jats:sup>) by immunohistochemistry on human <jats:italic>ex\u00a0vivo<\/jats:italic> skin. UVB\u2010induced expression of matrix metalloprotease\u20101 (MMP\u20101) was determined from full thickness skin by RT\u2010qPCR. Modification of the fibroblast secretome by HSA was studied by mass\u2010spectrometry\u2010based proteomics. In a full\u2010face, double blind, vehicle\u2010controlled trial HSA was assessed for its effects on conspicuous facial pore size and degree of pigmentation of age spots in Caucasian women over an 8\u2010week period.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>HSA was obtained in enantiomeric pure, high yield (\u226580%). Collagen type I and type III levels were dose\u2010dependently increased (96% and 244%; <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01) <jats:italic>in\u00a0vitro<\/jats:italic> and collagen type III in <jats:italic>ex\u00a0vivo<\/jats:italic> skin by +57% (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01) by HSA. HSA also inhibited UVB\u2010induced MMP\u20101 gene expression (83%; <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01) and mitigated SBC induction (\u221234% vs. vehicle control) and reduced significantly UV\u2010induced p53 up\u2010regulation (\u221246% vs. vehicle control; <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01) in irradiated skin. HSA modified the fibroblast secretome with significant increases in proteins associated with the WNT pathway that could reduce melanogenesis and proteins that could modify dermal fibroblast activity and keratinocyte differentiation to account for the alleviation of conspicuous pores. Docking studies <jats:italic>in silico<\/jats:italic> and EC50 determination in reporter gene assays (EC50 5.5\u00a0\u00d7\u00a010<jats:sup>\u22126<\/jats:sup>\u00a0M) identified HSA as a peroxisomal proliferator activated receptor\u2010<jats:italic>\u03b1<\/jats:italic> (PPAR<jats:italic>\u03b1<\/jats:italic>) agonist. Clinically, HSA showed a statistically significant decrease of surface and volume of skin pores (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05) after 8\u00a0weeks of application and age spots became significantly less pigmented than the surrounding skin (contrast, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05) after 4\u00a0weeks.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>HSA acts as a PPAR<jats:italic>\u03b1<\/jats:italic> agonist to reduce the signs of age spots and conspicuous pores by significantly modulating the expression of p53, SBC, MMP\u20101 and collagen together with major changes in secreted proteins that modify keratinocyte, melanocyte and fibroblast cell behavior.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ics.12529","type":"journal-article","created":{"date-parts":[[2019,4,7]],"date-time":"2019-04-07T17:50:53Z","timestamp":1554659453000},"page":"240-256","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Bio\u2010derived hydroxystearic acid ameliorates skin age spots and conspicuous pores"],"prefix":"10.1111","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2410-6128","authenticated-orcid":false,"given":"R.","family":"Sch\u00fctz","sequence":"first","affiliation":[{"name":"DSM Nutritional Products Ltd. 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