The MC1R Gene and Youthful Looks

Abstract

Looking young for one's age has been a desire since time immemorial. This desire is attributable to the belief that appearance reflects health and fecundity. Indeed, perceived age predicts survival [1] and associates with molecular markers of aging such as telomere length [2]. Understanding the underlying molecular biology of perceived age is vital for identifying new aging therapies among other purposes, but studies are lacking thus far. As a first attempt, we performed genome-wide association studies (GWASs) of perceived facial age and wrinkling estimated from digital facial images by analyzing over eight million SNPs in 2,693 elderly Dutch Europeans from the Rotterdam Study. The strongest genetic associations with perceived facial age were found for multiple SNPs in the MC1R gene (p < 1 × 10(-7)). This effect was enhanced for a compound heterozygosity marker constructed from four pre-selected functional MC1R SNPs (p = 2.69 × 10(-12)), which was replicated in 599 Dutch Europeans from the Leiden Longevity Study (p = 0.042) and in 1,173 Europeans of the TwinsUK Study (p = 3 × 10(-3)). Individuals carrying the homozygote MC1R risk haplotype looked on average up to 2 years older than non-carriers. This association was independent of age, sex, skin color, and sun damage (wrinkling, pigmented spots) and persisted through different sun-exposure levels. Hence, a role for MC1R in youthful looks independent of its known melanin synthesis function is suggested. Our study uncovers the first genetic evidence explaining why some people look older for their age and provides new leads for further investigating the biological basis of how old or young people look.

Cells to Surgery Quiz: January 2019

“…a. A number of previous studies have identified the MC1R gene as having an influence on skin photoaging and pigmented spots (Elfakir et al, 2010;Jacobs et al, 2015;Suppa et al, 2011;Liu et al, 2016). Hamer et al did not find any significant association between MC1R variants and wrinkles, which implies that these variants may not influence facial wrinkle variation as measured in the RS cohort but may instead impact other skin aging phenotypes such as pigmented age spots.…”

DNA methylation age and perceived age in elderly Danish twins

“…Recently it has been estimated that approximately half of the variation of perceived age is due to genetic factors, whereas the other half is due to environmental influences (Gunn et al, 2009). The first GWAS of perceived age (Liu et al, 2016) performed in a sample of elderly Dutch individuals identified multiple SNPs in the MC1R gene, a pigmentation gene, to be associated with perceived age, and hence pointed to specific genetic variants. As epigenetic mechanisms are ubiquitous in aging processes, it can be expected that epigenetic variation also contributes to both the genetic and non-genetic component of perceived age.…”

“…Further associations to bone status were found by (Nielsen et al, 2015). Overall, the major sources of variation in perceived age were identified to be genetic and environmental factors to equal parts (Gunn et al, 2009), and recently (Liu et al, 2016) performed the first GWAS of perceived age and found variants in MC1R , a pigmentation gene, to be associated.…”

Principal component analysis of seven skin‐ageing features identifies three main types of skin ageing

“…In addition, PA was included in the analysis because it has been used recently as a phenotype to investigate lifestyle factors and genes for skin appearance . Independent observers who were blinded to chronological age assessed the same photos for PA using an ordinal scale of 10 age groups (with an average number of 27 assessments per image/participant and a minimum of 20) .…”