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

Ayelet Alpert, Yishai Pickman, Michael Leipold, Yael Rosenberg-Hasson, Xuhuai Ji, Renaud Gaujoux, Hadas Rabani, Elina Starosvetsky, Ksenya Kveler, Steven Schaffert, David Furman, Oren Caspi, Uri Rosenschein, Purvesh Khatri, Cornelia L. Dekker, Holden T. Maecker, Mark M. Davis, Shai S. Shen-Orr

Research output: Contribution to journalArticlepeer-review

Abstract

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 high-dimensional 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.

Original languageEnglish
Pages (from-to)487-495
Number of pages9
JournalNature Medicine
Volume25
Issue number3
DOIs
StatePublished - 1 Mar 2019

All Science Journal Classification (ASJC) codes

  • General Biochemistry,Genetics and Molecular Biology

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