# Immune and inflammatory system changes in SuperAgers

> **NIH NIH U19** · NORTHWESTERN UNIVERSITY · 2021 · $711,656

## Abstract

ABSTRACT (Project 2)
 Immune and inflammatory system functions are important to respond to infection, however, emerging
evidence suggests that alterations in these systems accompany normative aging and neurodegenerative disease
changes (like Alzheimer's disease, AD). Less deeply understood is the constitutive impact of these systems on
organs and cells throughout the life span. In the proposed work we will explore the potential impact of immune
and inflammatory processes on the brain and the influence of these processes on resistance and resilience to
age-related cognitive changes that contribute to SuperAging. The basis for this approach is the well documented
immune and inflammatory system changes noted in normative aging, the pro-inflammatory microglial changes
associated with aging and AD, and the emergence of well-validated genetic risk factors for AD that have
demonstrated the importance of immune and inflammatory system genes in risk for the disease. These findings
suggest the immune and inflammatory system may play both a role in acute responses to infection as well as
exert a long-term impact on brain health, age-related cognitive changes, and/or resilience to brain-related
diseases.
 Project 2 of the SuperAging Consortium will explore this question through the study of unique individuals
within the general population who exhibit the phenotype of cognitive SuperAging – a trait defined as a two-
decade, or greater, superiority of memory capacity when compared to age-matched peers. We propose that
immune and inflammatory system function is related to the cognitive resilience seen in SuperAging individuals –
in the opposing way that it is related to risk for AD. We hypothesize that SuperAgers (SA) will demonstrate a
shift toward neuroprotection and lower pro-inflammatory profiles compared to Control and AD participants and
that these differences will clarify mechanisms of resilience to age-related phenomena. These hypotheses will be
pursued through three aims. In Aim 1 we will profile the individual transcriptomes of microglia and other cells in
brain tissue from SAs, Controls, and AD participants. In Aim 2 we will examine three different measures of the
adaptive immune and inflammatory systems – cytokine levels, T- and B-cell receptor repertoires, and antibody
profiles – in peripheral samples from SAs, Controls, and AD participants. Lastly, in Aim 3, we will investigate the
DNA sequence variations in ~500 different immune and inflammatory system genes in SAs and Controls. This
study design will allow us to unravel the link between potentially modifiable immune and inflammatory processes
and resistance to age-related decline of cognitive capacity.

## Key facts

- **NIH application ID:** 10276528
- **Project number:** 1U19AG073153-01
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Matt Huentelman
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $711,656
- **Award type:** 1
- **Project period:** 2021-09-30 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10276528

## Citation

> US National Institutes of Health, RePORTER application 10276528, Immune and inflammatory system changes in SuperAgers (1U19AG073153-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10276528. Licensed CC0.

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