Skin aging is a continuous process that affects skin appearance and function manifesting by several outcomes such as wrinkling and sagging. Researchers have identified impacting environmental factors (sun exposure, smoking, etc..) and several molecular mechanisms leading to skin aging. Recently, genome wide association studies (GWAS) have led to new insights into the molecular mechanisms of skin aging. Since individual SNP associations in GWAS explain only a small fraction of the genetic impact in complex polygenic phenotypes, we applied the Gene Set Enrichment Analysis on the genotype data obtained from 502 very-well characterized women to identify biological pathways associated with four major outcomes of skin aging, namely photoaging, solar lentigines, wrinkling, and sagging. This analysis revealed new relevant pathways and genes, some likely specific of skin aging such as the WNT7B and PRKCA genes in the “melanogenesis” pathway, some likely involved in global aging such as the DDB1 gene in the “nucleotide excision repair” pathway, not picked up in the previously published GWAS. Overall, our results suggest that photoaging, solar lentigines, wrinkling, and sagging involve specific molecular mechanisms such as “proteasome” and “mTOR signaling pathway” but also shared molecular mechanisms such as “nucleotide excision repair”.

Gene Set Enrichment Analysis identifies biological networks associated with skin aging