# High resolution longitudinal immune monitoring for elucidating immune aging dynamics

> **NIH NIH P01** · STANFORD UNIVERSITY · 2021 · $3,700,000

## Abstract

Since 2007, we have annually tracked the dynamics of immune system changes with the Stanford Ellison
Longitudinal Aging (SELA) cohort, which consists of ~150 young (20-40) and old (60+) individuals of various
ages for which we determined cell subset phenotypes and cytokine responses at high resolution, whole blood
gene expression, serum cytokines, HAI response to annual flu vaccination, and a standardized clinical
evaluation. Given the length of time and the depth of profiling, the SELA cohort is a unique resource.
Using a novel systems approach which leverages the high-dimensional and longitudinal nature of the data
allowed us to gain increased insight into immune-aging and describe an individual’s immune baseline
homeostatic state as shifting slowly along a continuum and a trajectory, well beyond what can normally be
obtained from cross-sectional analyses. We utilized this to build a reliable metric of immune-age (IMM-AGE),
which captures a life-long process of change in immune cell subset composition and cell responses in a single
value. IMM-AGE only partially correlates with chronological age and yet has prognostic clinical value with respect
to all-cause-mortality in healthy older adults beyond well-established risk factors. In addition, using SELA we
have identified several strong links between cardiovascular disease and immune-based predictive markers,
correlative to IMM-AGE, that offer better and earlier detection than existing standard clinical tests. Understanding
human immune variation and aging through the lens of a quantitative patterned process led us to testable
hypotheses which we will explore here. Specifically, our two research projects address two questions – (1) what
drives immune-aging; and (2) how does it relate to immune response, disease severity, and treatment? To
answer these questions we will continue the longitudinal profiling of SELA, now with more epigenetic and
environmental data, and recruit additional cohorts: a healthy twin cohort (ages 40-60), a current gap in SELA
and one informative of early immune aging; a cohort of older adults vigorously exercising and living well which
can be leveraged to distinguish features of biological aging and those modifiable by lifestyle and for which we
have measured immune parameters in 2011; and two additional cohorts, first of heart transplant subjects and
second of subjects in the Women’s Health Initiative with retrospective information on cardiovascular state. These
latter cohorts will allow us to test hypotheses raised from our published studies on the relation of immune-aging
to cardiovascular disease and its connection to flu history, an observed epidemiological association whose
mechanism has been unclear to date. Last, we will use post-vaccination samples from SELA collected over 12+
years to map flu-specific B and T cell response history and test whether this information, coupled with immune-
age, can help predict flu vaccine responses in older adults, a currently unsol...

## Key facts

- **NIH application ID:** 10190557
- **Project number:** 1P01AI153559-01A1
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Mark Morris Davis
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $3,700,000
- **Award type:** 1
- **Project period:** 2021-09-21 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10190557

## Citation

> US National Institutes of Health, RePORTER application 10190557, High resolution longitudinal immune monitoring for elucidating immune aging dynamics (1P01AI153559-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10190557. Licensed CC0.

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