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Abstract
Smoking-associated DNA methylation (DNAm) signatures are reproducible among studies of mostly European descent, with mixed evidence if smoking accelerates epigenetic aging and its relationship to longevity. We evaluated smoking-associated DNAm signatures in the Costa Rican Study on Longevity and Healthy Aging (CRELES), including participants from the high longevity region of Nicoya. We measured genome-wide DNAm in leukocytes, tested Epigenetic Age Acceleration (EAA) from five clocks and estimates of telomere length (DNAmTL), and examined effect modification by the high longevity region. 489 participants had a mean (SD) age of 79.4 (10.8) years, and 18% were from Nicoya. Overall, 7.6% reported currently smoking, 35% were former smokers, and 57.4% never smoked. 46 CpGs and five regions (e.g. AHRR, SCARNA6/SNORD39, SNORA20, and F2RL3) were differentially methylated for current smokers. Former smokers had increased Horvath’s EAA (1.69-years; 95% CI 0.72, 2.67), Hannum’s EAA (0.77-years; 95% CI 0.01, 1.52), GrimAge (2.34-years; 95% CI1.66, 3.02), extrinsic EAA (1.27-years; 95% CI 0.34, 2.21), intrinsic EAA (1.03-years; 95% CI 0.12, 1.94) and shorter DNAmTL (− 0.04-kb; 95% CI − 0.08, − 0.01) relative to non-smokers. There was no evidence of effect modification among residents of Nicoya. Our findings recapitulate previously reported and novel smoking-associated DNAm changes in a Latino cohort.
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1 University of California, Berkeley, Division of Environmental Health Sciences, School of Public Health and Center for Computational Biology, Berkeley, USA (GRID:grid.47840.3f) (ISNI:0000 0001 2181 7878)
2 University College London, UCL Cancer Institute, London, UK (GRID:grid.83440.3b) (ISNI:0000000121901201)
3 University of California San Francisco, School of Medicine, San Francisco, USA (GRID:grid.266102.1) (ISNI:0000 0001 2297 6811)
4 University of Costa Rica (UCR), School of Health Technology, Faculty of Medicine, San José, San Pedro, Costa Rica (GRID:grid.412889.e) (ISNI:0000 0004 1937 0706)
5 University of Victoria, Faculty of Human and Social Development, School of Health Information Science, Victoria, Canada (GRID:grid.143640.4) (ISNI:0000 0004 1936 9465)
6 University of British Columbia, Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, and BC Children’s Hospital Research Institute, Vancouver, Canada (GRID:grid.17091.3e) (ISNI:0000 0001 2288 9830)
7 Universidad de Costa Rica, Centro Centroamericano de Población (CCP), San José, Costa Rica (GRID:grid.412889.e) (ISNI:0000 0004 1937 0706)
8 University of California, Berkeley, Division of Health Policy and Management, School of Public Health, Berkeley, USA (GRID:grid.47840.3f) (ISNI:0000 0001 2181 7878)
9 Stanford University, Department of Epidemiology and Population Health and Department of Medicine, School of Medicine, Palo Alto, USA (GRID:grid.168010.e) (ISNI:0000000419368956)