The U.S. population is growing older and by 2030 21% of the population will be over the age of 65. Many of the diseases associated with aging directly correlate with chronic systemic inflammation. Previous studies show that aging results in less naïve lymphocytes and an increased production of highly differentiated effector lymphocytes, likely due to repeated stimulation of the immune system. These highly differentiated effector lymphocytes (called immunosenescence) spontaneously secrete pro-inflammatory mediators. What is driving immunosenescence is unknown. We hypothesize that this immunosenescent behavior is more prevalent in older individuals due to a higher percentage of persistent or latent viral infections accumulated over a lifetime. We also hypothesize that the repeated T cell stimulation from a high viral burden results in an increase of immunosenescent markers and inflammatory mediators among older patients. In this study we collected blood plasma from older subjects aged 65 and older and young subjects between the ages of 20 and 40 to compare the presence of plasma inflammatory markers (using a bead array assays system) and evidence of T immunosenescence and activation (using flow cytometry). We further sought to determine whether any differences seen correlate with evidence of cytomegalovirus (CMV) infection, a classic chronic viral infection capable of establishing lifelong latency. We hypothesize that the immunosenexcent T cell phenotype and plasma inflammatory mediators will show a correlation to evidence of CMV viral burden, and the frequency of T cell activation will be higher in older adults compared to younger adults.

We hypothesize that immunosenescence is more prevalent in older individuals due to a higher lifetime prevalence of viral infections, especially those capable of establishing latency, which results in repetitive T cell stimulation due to recurrent reactivation. We also hypothesize that the immunosenescent T cell phenotype and plasma inflammatory mediators will exhibit a correlation to evidence of CMV viral burden, and the frequency of T cell activation will be higher in older adults.

To address this hypothesis, we analyzed 122 samples from subjects aged 21-40 years-old and 127 samples from subjects who are 65 years or older. Women and men are included in both cohorts, but the study is weighted more towards women due to their longer life expectancy. Inflammatory mediator proteins (chemokines and cytokines) were measured using cytokine bead array kits from Becton Dickinson. The cytokines assayed were IL-1ß, IL-1ra, IL-2, IL-4, IL-6, IL-10, IL-12, IL-17, IFN-gamma, TGF-ß, TNF-alpha, soluble TNFR 1 and 2, RANTES, MIGF, IP-10, and IL-8. Lymphocyte phenotyping was performed on CD4 and CD8 T Cells by flow cytometry using markers of cellular differentiation (naive, central memory, effector memory), immunosenescence (CD57, TEMRA), and cellular activation (HLA-DR and CD38). Finally, the above markers of immunosenescence and inflammation were correlated with cytomegalovirus (CMV) antibody titers.