Widowhood, immune aging, and mortality in older Americans: evidence from the US Health and Retirement Study

Widowhood has been linked to increased mortality risk, particularly among men, but the biological mechanisms remain unknown. Given the impacts of stress on immune function, we hypothesized that widowhood leads to increased mortality by impacting immunity.

Data from 8410 US adults aged 56 and older in the Health and Retirement Study, including flow cytometry of blood samples, survey data, and mortality, were analyzed. Associations between widowhood, immunosenescence (measured by the CD8+:CD4+ Ratio, EMRA CD4+:Naïve CD4+ Ratio, EMRA CD8+:Naïve CD8+ Ratio), and mortality were examined using linear regression and Cox proportional hazards models.

Men and women who experienced widowhood and who showed signs of more advanced immune-system aging were at increased mortality risk. Widowed men consistently had more aged T-cells than married men across multiple measures. However, among widowed women, this association was observed only for the EMRA CD4+:Naïve CD4+ ratio. Elevated levels of aged T-cells partially mediated the relationship between widowhood and mortality, with a stronger mediating effect observed in men than in women.

Our findings indicate that bereavement accelerates immunosenescence, contributing to the increased mortality risk observed in widowed men and revealing a biologically grounded pathway with potential for amelioration.