Characterization of Aging of the Immune System and the Impact of Aging on Immune Response

Aging of the immune system leads to a decline in immune response, increasing the vulnerability to infectious, cardiovascular, metabolic, and autoimmune diseases. At the cellular level, the composition of innate and adaptive immune cell subsets changes over time. We identified a trajectory of immune aging by longitudinally tracking population levels using peripheral blood samples collected from healthy young and older adults (as part of the Stanford-Ellison aging study). The position of each individual on this trajectory was captured by the IMM-AGE score, providing additional clinical benefit beyond what is captured by chronological age and standard clinical lab tests. So far, the IMM-AGE score of an individual was determined from peripheral blood mononuclear cell (PBMC) samples measured by Mass cytometry (CyTOF), using a T-cell centric panel that mainly allowed for the identification of T cell subsets. To improve the accuracy and utility of the IMM-AGE metric we included markers for the identification of B cell subsets and subsets derived from the myeloid lineage. The immune cell subsets used for the calculation of IMM-AGE imply that one’s location on the IMM-AGE trajectory may indicate the individual’s capacity to mount an immune response. To explore this concept we employed CyTOF and simultaneously measured 85 unique markers associated with immune system functionality upon stimulus, exhaustion, senescence, and metabolic capacity, in 40 young and old individuals. This allowed for an assessment of the relationship between metabolic cell state and functionality in the context of immune aging.