Association of Immune Cell Subsets with Longevity: The Cardiovascular Health Study

Abstract Background Changes in the immune system are a potential biological mechanism of aging. We investigated the association of circulating immune cell subsets with age at death and survival to age 90. Methods Immune cell phenotypes were measured at baseline in 1,625 adults, aged 70 to 85 years, in the Cardiovascular Health Study. We selected five primary immune cell subsets: gamma-delta T-cells, natural killer cells, CD8+ T effector memory CD45RA expressing cells (TEMRA) cells, ratio of CD4+ to CD8+ cells, and ratio of naïve to memory CD8+ cells. We used linear regression and Poisson models, adjusting for demographics and clinical factors; and tested for effect modification by sex and race. In a secondary analysis, we investigated 23 additional immune cell subsets, using the Holm-Bonferroni method to adjust for multiple comparisons. Results No primary immune cell subsets were significantly associated with longevity. Two secondary subsets were significantly associated with age at death. Each SD higher proportion of CD4+CD57+ cells was associated with a 0.64-year earlier death (95%CI:-0.99,-0.30) and each SD higher proportion of CD4+CD28-CD57+ cells was associated with a 0.54-year earlier death (95% CI:-0.87,-0.21). Several subsets had significant interactions with sex and race in the fully adjusted model of age at death. A higher proportion of CD4+CD57+ T-cells was significantly associated with lower likelihood of survival to age 90 (RR: 0.79) and 1.07-year earlier age at death in males, but not in females. Conclusions Our results suggest that CD4+CD57+ cells are associated with earlier death and this relationship was stronger in males than females.