A clinically meaningful metric of immune age derived from high-dimensional longitudinal monitoring

Abstract

<p class="first" id="P3">Immune responses generally decline with age. However, the dynamics of this process at the individual level have not been characterized, hindering quantification of an individual’s immune age. Here, we use multiple ‘omics’ technologies to capture population- and individual-level changes in the human immune system of 135 healthy adult individuals of different ages sampled longitudinally over a nine-year period. We observed high inter-individual variability in the rates of change of cellular frequencies that was dictated by their baseline values, allowing identification of steady-state levels toward which a cell subset converged and the ordered convergence of multiple cell subsets toward an older adult homeostasis. These data form a highdimensional trajectory of immune aging (IMM-AGE) that describes a person’s immune status better than chronological age. We show that the IMM-AGE score predicted all-cause mortality beyond well-established risk factors in the Framingham Heart Study, establishing its potential use in clinics for identification of patients at risk. </p><div class="section"> <a class="named-anchor" id="S1"> <!-- named anchor --> </a> <h5 class="section-title" id="d5613313e339">Reporting Summary.</h5> <p id="P4">Further information on experimental design is available in the Nature Research Reporting Summary linked to this article. </p> </div>