A systematic review of skin ageing genes: gene pleiotropy and genes on the chromosomal band 16q24.3 may drive skin ageing

Abstract

Skin ageing is the result of intrinsic genetic and extrinsic lifestyle factors. However, there is no consensus on skin ageing phenotypes and ways to quantify them. In this systematic review, we first carefully identified 56 skin ageing phenotypes from multiple literature sources and sought the best photo-numeric grading scales to evaluate them. Next, we conducted a systematic review on all 44 Genome-wide Association Studies (GWAS) on skin ageing published to date and identified genetic risk factors (2349 SNPs and 366 genes) associated with skin ageing. We identified 19 promising SNPs found to be significantly (p-Value < 1E−05) associated with skin ageing phenotypes in two or more independent studies. Here we show, using enrichment analyses strategies and gene expression data, that (1) pleiotropy is a recurring theme among skin ageing genes, (2) SNPs associated with skin ageing phenotypes are mostly located in a small handful of 44 pleiotropic and hub genes (mostly on the chromosome band 16q24.3) and 32 skin colour genes. Since numerous genes on the chromosome band 16q24.3 and skin colour genes show pleiotropy, we propose that (1) genes traditionally identified to contribute to skin colour have more than just skin pigmentation roles, and (2) further progress towards understand the development of skin pigmentation requires understanding the contributions of genes on the chromosomal band 16q24.3. We anticipate our systematic review to serve as a hub to locate primary literature sources pertaining to the genetics of skin ageing and to be a starting point for more sophisticated work examining pleiotropic genes, hub genes, and skin ageing phenotypes.

Comparisons between eyebags, droopy eyelids, and eyebrow positioning identified by photo‐numeric scales or identified by written descriptive scales: Insights from the Singapore/Malaysia cross‐sectional genetics epidemiology study (SMCGES) cohort

“…In our recent systematic review of skin ageing, 10 we found that the quantification of skin ageing phenotypes in the field can be broadly classified into two categories: quantification using a written descriptive scale and quantification using a photo‐numeric scale.…”

Genetical Signature – An Example of Personalized Skin Aging Investigation with Possible Implementation to Clinical Practice

“…Recently performed genome-wide association studies (GWASs) and other original research works laid the groundwork for a personalized approach to healthcare, where a niche for more effective skincare approaches certainly exists [20][21][22]. In the literature, there are different types of investigations with different objectives, where some of them are orientated to a thorough pathophysiological and genetical analysis [3,22], while others are focused on a more practical approach, trying to find the best way to utilize scientific findings for clinical use [6,10,11]. Our work stands out from both categories by combining routine laboratory investigations with molecular genotyping results offering regular blood tests that would depend on individual skinassociated genotypes.…”

Molecular biomarkers of skin aging and cosmetic

“…Additionally, Ng & Chew (2022) [3] performed a systematic review of 44 GWAS studies on skin aging and identified 19…”

“…Skin aging compared to other organs is a complex process influenced by two main factors: intrinsic, or genetic; and extrinsic, or environmental [1,2] . Since skin aging suffers from both genetic and environmental influences, the study of these variables is extremely important for precision medicine, in which treatments can be customized according to individual needs [3,4] .…”