Global downregulation of pigmentation-associated genes in human premature hair graying

Premature hair graying, or canities, is a complex multi-factorial process with negative effects on affected individuals. The aim of the present study was to investigate the possible underlying mechanisms of premature hair graying at the genetic level. A total of 5 unrelated Han Chinese individuals presenting with premature hair graying (25-40 years old, with >1% hair affected) were enrolled in the present study. RNA sequencing was performed to identify gene expression changes between the follicular cells of grey and black hair from the cohort. A total of 127 differentially expressed genes (DEGs) were identified. These DEGs were overrepresented in categories associated with the pigmentation pathway, with a decreased expression of key genes responsible for melanin synthesis. Of note, the decreased expression of certain transcription factors and the increased expression of certain precursor microRNAs observed may explain for the downregulation of certain other DEGs, which were identified as their targets via Starbase v2 and Integrated Motif Activity Response Analysis. The DEGs were also enriched in terms associated with the nervous system, indicating that neural disturbances may also have certain roles in premature hair graying. Of note, five of the downregulated DEGs were associated with aging according to the JenAge Aging Factor Database. To the best of our knowledge, the present study was the first genome-wide survey of the gene expression profile associated with premature hair graying. Dysfunction of the melanin biosynthesis pathway is probably the direct cause of hair graying and the present results provide valuable clues for further functional and mechanistic investigation.