biostudies-literatureUnknownSchmithorst VNHLBI NIH HHSLife expectancy continues to increase in the high-income world due to advances in medical care; however, quality of life declines with increasing age due to normal aging processes. Current research suggests that various aspects of aging are genetically modulated and thus may be slowed via genetic modification. Here, we show evidence for epigenetic modulation of the aging process in the brain from over 1800 individuals as part of the Framingham Heart Study. We investigated the methylation of genes in the protocadherin (PCDH) clusters, including the alpha (<i>PCHDA</i>), beta (<i>PCDHB</i>), and gamma (<i>PCDHG</i>) clusters. Reduced <i>PCDHG</i>, elevated <i>PCDHA</i>, and elevated <i>PCDHB</i> methylation levels were associated with substantial reductions in the rate of decline of regionalmedRxiv : the preprint server for health sciences2024.04.21.24306143https://www.ebi.ac.uk/biostudies/studies/S-EPMC11071558biostudies-literatureComplex Regulation of Protocadherin Epigenetics on Aging-Related Brain Health.PMC11071558R01 HL128818R01 HL152740Bais AGabriel GLo CSchmithorst VWilliams KWallace JCeschin RLopez OCohen ABadaly DMartin LJLee VPanigrahy AfalseComplex Regulation of Protocadherin Epigenetics on Aging-Related Brain Health.Life expectancy continues to increase in the high-income world due to advances in medical care; however, quality of life declines with increasing age due to normal aging processes. Current research suggests that various aspects of aging are genetically modulated and thus may be slowed via genetic modification. Here, we show evidence for epigenetic modulation of the aging process in the brain from over 1800 individuals as part of the Framingham Heart Study. We investigated the methylation of genes in the protocadherin (PCDH) clusters, including the alpha (<i>PCHDA</i>), beta (<i>PCDHB</i>), and gamma (<i>PCDHG</i>) clusters. Reduced <i>PCDHG</i>, elevated <i>PCDHA</i>, and elevated <i>PCDHB</i> methylation levels were associated with substantial reductions in the rate of decline of regional2024-01-01T00:00:00Z2024 Apr2026-04-13T03:27:17.655Z2026-04-13T03:12:59.981ZS-EPMC110715583871216510.1101/2024.04.21.24306143