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

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. 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. After adjusting for demographic factors, immigrants had 2.53-year lower GrimAge2 measures (95%CI: −3.44, −1.63, <i>p</i> &lt; 0.001) compared to non-immigrants. U.S. citizens had 1.98-year higher GrimAge2 measures (95%CI: 0.66, 3.30, <i>p</i> = 0.005) compared to non-citizens. The GrimAge2 associations with immigrant status (β = -1.04-years, 95%CI: −1.87, −0.21, <i>p</i> = 0.02) and citizenship (β = 1.35-years, 95%CI: 0.38, 2.32, <i>p</i> = 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. 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. This study explored whether being an immigrant or a U.S. citizen is linked to aging, based on changes in DNA methylation that can predict health and lifespan. Using data from 2,336 U.S. adults, we compared seven different DNA methylation-based aging measures between immigrants and non-immigrants, as well as citizens and non-citizens. Immigrants had younger DNA methylation ages than non-immigrants. For example, one marker (GrimAge2) showed that immigrants were about 2.5 years younger. U.S. citizens had older DNA methylation ages than non-citizens, about 2 years older in GrimAge2. These differences became smaller when considering lifestyle and health factors, showing that behaviors and environment matter. Immigrants and citizens also had different estimated levels of certain blood proteins linked to aging, like C-reactive protein (inflammation) and adrenomedullin (vascular health). Our findings support the idea that immigrants may have better health (the “immigrant mortality advantage”). Overall, this study shows how DNA methylation-based aging markers can help us understand how social and environmental factors affect health differences between groups.