Immigrant status and citizenship relationships with epigenetic aging in a representative sample of United States adults

Background: Immigrant status and citizenship influence health and well-being, yet their associations with DNA methylation (DNAm)-based biomarkers of aging–key predictors of healthspan and lifespan, also known as epigenetic aging–remain underexplored. Methods: Using a representative sample of 2,336 United States (U.S.) adults from the 1999–2000 and 2001–2002 cycles of the National Health and Nutrition Examination Survey (NHANES), we analyzed cross-sectional associations of immigrant status and U.S. citizenship with seven epigenetic aging biomarkers: HannumAge, HorvathAge, SkinBloodAge, PhenoAge, GrimAge2, DNAm Telomere Length, and DunedinPoAm. Results: After adjusting for demographic factors, immigrants had 2.53-year lower GrimAge2 measures (95%CI: −3.44, −1.63, p < 0.001) compared to non-immigrants. U.S. citizens had 1.98-year higher GrimAge2 measures (95%CI: 0.66, 3.30, p = 0.005) compared to non-citizens. The GrimAge2 associations with immigrant status (β = -1.04-years, 95%CI: −1.87, −0.21, p = 0.02) and citizenship (β = 1.35-years, 95%CI: 0.38, 2.32, p = 0.02) were attenuated after adjusting for other lifestyle/health variables. Immigrant status and citizenship were associated with estimated levels of several GrimAge2 DNAm component proteins, including adrenomedullin and C-reactive protein. Conclusion: Our results support the paradigm of the immigrant mortality advantage and highlight the potential value of epigenetic age measures in studying socioeconomic and broader factors influencing citizen and immigrant health.