Novel Gene Expression Profile of Women with Intrinsic Skin Youthfulness by Whole Transcriptome Sequencing.
While much is known about genes that promote aging, little is known about genes that protect against or prevent aging, particularly in human skin. The main objective of this study was to perform an unbiased, whole transcriptome search for genes that associate with intrinsic skin youthfulness. To accomplish this, healthy women (n = 122) of European descent, ages 18-89 years with Fitzpatrick skin type I/II were examined for facial skin aging parameters and clinical covariates, including smoking and ultraviolet exposure. Skin youthfulness was defined as the top 10% of individuals whose assessed skin aging features were most discrepant with their chronological ages. Skin biopsies from sun-protected inner arm were subjected to 3'-end sequencing for expression quantification, with results verified by quantitative reverse transcriptase-polymerase chain reaction. Unbiased clustering revealed gene expression signatures characteristic of older women with skin youthfulness (n = 12) compared to older women without skin youthfulness (n = 33), after accounting for gene expression changes associated with chronological age alone. Gene set analysis was performed using Genomica open-access software. This study identified a novel set of candidate skin youthfulness genes demonstrating differences between SY and non-SY group, including pleckstrin homology like domain family A member 1 (PHLDA1) (p = 2.4x10-5), a follicle stem cell marker, and hyaluronan synthase 2-anti-sense 1 (HAS2-AS1) (p = 0.00105), a non-coding RNA that is part of the hyaluronan synthesis pathway. We show that immunologic gene sets are the most significantly altered in skin youthfulness (with the most significant gene set p = 2.4x10-5), suggesting the immune system plays an important role in skin youthfulness, a finding that has not previously been recognized. These results are a valuable resource from which multiple future studies may be undertaken to better understand the mechanisms that promote skin youthfulness in humans.
Department of Dermatology, Stanford University School of Medicine, Redwood City, California, United States of America.
Jin
J
Xu
Department of Pharmaceutical Sciences, University of California Irvine, Irvine, California, United States of America.
Robert C
RC
Spitale
Department of Dermatology, Stanford University School of Medicine, Redwood City, California, United States of America.
Linna
L
Guan
Department of Dermatology, Stanford University School of Medicine, Redwood City, California, United States of America.
Ryan A
RA
Flynn
Department of Dermatology, Stanford University School of Medicine, Redwood City, California, United States of America.
Eduardo A
EA
Torre
Department of Dermatology, Stanford University School of Medicine, Redwood City, California, United States of America.
Rui
R
Li
Department of Dermatology, Stanford University School of Medicine, Redwood City, California, United States of America.
Inbar
I
Raber
Department of Dermatology, Stanford University School of Medicine, Redwood City, California, United States of America.
Kun
K
Qu
Nu Skin International, Provo, Utah, United States of America.
Dale
D
Kern
Nu Skin International, Provo, Utah, United States of America.
Helen E
HE
Knaggs
Department of Dermatology, Stanford University School of Medicine, Redwood City, California, United States of America.
Howard Y
HY
Chang
Department of Dermatology, Stanford University School of Medicine, Redwood City, California, United States of America.
Anne Lynn S
AL
Chang
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D063990:Gene Ontology; D014453:Glucuronosyltransferase / Q000235:genetics; D006801:Humans; D000076002:Hyaluronan Synthases; D008875:Middle Aged; D010641:Phenotype; D022661:RNA, Untranslated / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000378:metabolism*; D015595:Skin Aging / Q000208:ethnology / Q000235:genetics*; D012907:Smoking; D014157:Transcription Factors / Q000235:genetics; D059467:Transcriptome / Q000235:genetics* / Q000528:radiation effects; D014466:Ultraviolet Rays; D044465:White People / Q000235:genetics; D055815:Young Adult
C491923:PHLDA1 protein, human; D022661:RNA, Untranslated; D014157:Transcription Factors; D014453:Glucuronosyltransferase; C101754:HAS2 protein, human; D000076002:Hyaluronan Synthases