MAIN BODY: A total of 48 studies were included, revealing 30 loci that were confirmed to be associated with skin ageing by multiple studies (e.g., AFG3L1P: odds ratio 1.133 95% confidence interval [1.044, 1.222]; BPIFA3: 1.859 [1.567, 2.151]; CLPTML1: 1.164 [1.0.99, 1.229]; CPNE7: 0.905 [0.852-0.958]; DEF8: 1.186 [1.042, 1.331]; IRF4: 1.260 [1.025, 1.495]; MYO16: 2.303 [1.697, 2.908]; PRDM16: 1.105 [1.084, 1.127]; RORA: 1.391 [1.206, 1.577]; SPG7: 0.922 [0.897, 0.947]; SPON1: 2.214 [1.204, 3.225]; SPTLC1: 1.464 [1.432, 1.495]; TYR: 1.175 [1.007, 1.343]). The lack of significance for many loci may be due to studies analysing different SNPs within the same locus, weakening the overall associations. Several loci were associated with specific phenotypic categories (e.g., skin colour related, skin cancer related, wrinkling and sagging related), suggesting shared biological pathways are involved in the pathogenesis of different skin ageing phenotypes. This pattern was also observed in several of the loci that do not have a significant overall association with skin ageing.
CONCLUSION: Despite significant heterogeneity among the included studies and the use of subjective visual methods for phenotype assessment, our review highlights the critical role of fundamental biological processes, such as development and cellular organisation, in skin ageing. Future research that targets the same SNP across multiple populations could strengthen the association of additional loci with skin ageing. Further investigation into these underlying biological processes would significantly advance our understanding of the pathogenesis of skin ageing phenotypes.
RESULTS: We analyzed 1451 extant genomes, 189 AAs from India and Malaysia, and 43 ancient genomes from S&SEA. Population structure analysis reveals neither language nor geography appropriately correlates with genetic diversity. The inconsistency between "language and genetics" or "geography and genetics" can largely be attributed to ancient admixture with East Asian populations. We estimated a pre-Neolithic origin of AA language speakers, with shared ancestry between Indian and Malaysian populations until about 470 generations ago, contesting the existing model of Neolithic expansion of the AA culture. We observed a spatio-temporal transition in the genetic ancestry of SEA with genetic contribution from East Asia significantly increasing in the post-Neolithic period.
CONCLUSION: Our study shows that contrary to assumptions in many previous studies and despite having linguistic commonality, Indian AAs have a distinct genomic structure compared to Malaysian AAs. This linguistic-genetic discordance is reflective of the complex history of population migration and admixture shaping the genomic landscape of S&SEA. We postulate that pre-Neolithic ancestors of today's AAs were widespread in S&SEA, and the fragmentation and dissipation of the population have largely been a resultant of multiple migrations of East Asian farmers during the Neolithic period. It also highlights the resilience of AAs in continuing to speak their language in spite of checkered population distribution and possible dominance from other linguistic groups.