# The effects of immune-age on immune-response and the molecular mechanisms which drive it

> **NIH NIH P01** · STANFORD UNIVERSITY · 2022 · $644,856

## Abstract

PROJECT SUMMARY
The immune system is a complex system which continuously changes as it responds to the internal and external
environments, making it very difficult to understand the variation between individuals and its functional
implications. Our SELA derived trajectory captures the variation in immune-cell composition between individuals,
thus describes the conserved cascade of cell compositional changes occurring during healthy aging. An
individual’s high-dimensional immune cell composition can be translated into a quantitative measure describing
its position along this immune-aging cascade reflecting the immune-age. Individuals’ immune-age alters as they
advance at different rates along this patterned trajectory, resulting in high inter-individual variation at baseline.
We hypothesize that the immune-aging trajectory is conserved between individuals due to epigenetic cell-specific
alterations that are induced through an interaction with common physiological and environmental changes that
occur with age. Furthermore, we hypothesize that this the baseline variation in immune-age between individuals
has functional implications during immune response, which ultimately may lead to variability in clinical outcome,
which is observed for the majority of insults and therapies. Project 1 is designed to enrich and refine our immune
age metric by expanding our cohort (adding 40-60 years-old twins) and by measuring in addition immune cell
types, factors (cytokines, epigenetic modifications, and metabolomics) found to be in correlation with immune
aging. Furthermore, we will identify factors that drive progression along the immune age trajectory. In addition,
we will gain comprehensive insight into the way age and immune history affect adaptive (B and T) responses
elicited by annual influenza vaccination in the old. Lastly, leveraging the 12+ years of bio-banked SELA samples
pre and post seasonal influenza vaccination we will test the hypothesis that molecular immune responses differ
as a function of baseline immune-age and decouple immune dynamics that are caused by different vaccine
compositions from those that are caused by immune-age. We will combine the latter molecular features
correlated with immune age with data on flu specific adaptive responses to obtain, for the first-time
comprehensive understanding of vaccine responses in older adults, a risk group for infection. We hope that
combining immune-age with B and T flu history, will allow to predict influenza vaccine response from baseline,
an unsolved problem of high concern for world health.

## Key facts

- **NIH application ID:** 10491680
- **Project number:** 5P01AI153559-02
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Shai Shlomo Shen-Orr
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $644,856
- **Award type:** 5
- **Project period:** 2021-09-21 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10491680

## Citation

> US National Institutes of Health, RePORTER application 10491680, The effects of immune-age on immune-response and the molecular mechanisms which drive it (5P01AI153559-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10491680. Licensed CC0.

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