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<p>Skin ageing is a multifaceted process influenced by both intrinsic genetic factors and extrinsic environmental exposures. This review explores the genetic variants and molecular mechanisms underlying skin ageing phenotypes, while identifying gaps in current research to inform future studies. A systematic search of the Scopus and Web of Science databases was conducted, with articles screened based on criteria including a focus on human genetic association studies and indexing in either Scopus or the Institute for Scientific Information (ISI) Web of Science. The quality of included studies was assessed using the Q-Genie tool. Thirteen studies met the inclusion criteria, collectively analysing 115 single nucleotide polymorphisms (SNPs) across 99 genes. The <i>OCA2</i> gene emerged as the most frequently investigated, consistently linked to hyperpigmentation. Overall, findings indicate that skin ageing phenotypes are associated with genes involved in collagen metabolism, melanogenesis, oxidative stress, and mechanical properties of the skin. Notably, <i>SPATA33</i> rs35063026 and <i>IRF4</i> rs12203592 polymorphisms exhibit pleiotropic effects, contributing to both wrinkling and pigmentation changes. Interestingly, some variants, such as <i>SPTLC1</i> rs7042102 and <i>REEP3</i> rs11961184, display paradoxical effects, underscoring the complexity of genetic modulation. Genes implicated in extracellular matrix (ECM) degradation, such as <i>SMYD3</i>, and those responsive to environmental pollutants, like <i>CYP1A1</i>, were associated with increased skin sagging. Conversely, variants in genes such as <i>COL1A2</i> and <i>COL13A1</i>, which support ECM integrity and skin resilience, were linked to protective effects. Despite these insights, many genetic associations remain poorly understood, highlighting substantial gaps in knowledge and the need for more comprehensive genetic research into skin ageing.</p>

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Deciphering the molecular clock: exploring molecular mechanisms and genetic influences on skin ageing

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年8月2日

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  • Horng Yih Ng,
  • Yuan Seng Wu,
  • Mohitosh Biswas,
  • Maw Shin Sim

摘要

Skin ageing is a multifaceted process influenced by both intrinsic genetic factors and extrinsic environmental exposures. This review explores the genetic variants and molecular mechanisms underlying skin ageing phenotypes, while identifying gaps in current research to inform future studies. A systematic search of the Scopus and Web of Science databases was conducted, with articles screened based on criteria including a focus on human genetic association studies and indexing in either Scopus or the Institute for Scientific Information (ISI) Web of Science. The quality of included studies was assessed using the Q-Genie tool. Thirteen studies met the inclusion criteria, collectively analysing 115 single nucleotide polymorphisms (SNPs) across 99 genes. The OCA2 gene emerged as the most frequently investigated, consistently linked to hyperpigmentation. Overall, findings indicate that skin ageing phenotypes are associated with genes involved in collagen metabolism, melanogenesis, oxidative stress, and mechanical properties of the skin. Notably, SPATA33 rs35063026 and IRF4 rs12203592 polymorphisms exhibit pleiotropic effects, contributing to both wrinkling and pigmentation changes. Interestingly, some variants, such as SPTLC1 rs7042102 and REEP3 rs11961184, display paradoxical effects, underscoring the complexity of genetic modulation. Genes implicated in extracellular matrix (ECM) degradation, such as SMYD3, and those responsive to environmental pollutants, like CYP1A1, were associated with increased skin sagging. Conversely, variants in genes such as COL1A2 and COL13A1, which support ECM integrity and skin resilience, were linked to protective effects. Despite these insights, many genetic associations remain poorly understood, highlighting substantial gaps in knowledge and the need for more comprehensive genetic research into skin ageing.