# Quantifying the genomic consequences of chronic social stress for accelerated aging

> **NIH NIH F32** · DUKE UNIVERSITY · 2020 · $64,926

## Abstract

PROJECT SUMMARY
 People that experience chronic exposure to unresolved social stress, including that induced by low
socioeconomic status or social isolation, exhibit increased risk of immune dysregulation, major diseases of aging,
and mortality itself. These observations have led to the hypothesis that social stress accelerates the process of
aging by altering some of same biological pathways that are also changed with age. Support for this idea has
come from a small number of well-characterized markers of inflammation and cellular senescence (e.g., IL-6
levels, CRP levels, and shortened leukocyte telomeres). However, we know much less about how changes in
gene regulation link experienced social stress to biological aging, in part because identifying the causal effects
of social stress on gene regulation remains a major challenge.
 Recent work in nonhuman primate animal models has helped overcome this challenge by showing a
direct causal relationship between chronic social stress and gene expression in immune cells. The goal of the
proposed research is to build on these models to address three outstanding questions about the relationship
between social stress and aging. First, does chronic, social subordination-induced social stress cause
accelerated aging in immune gene expression patterns, such that low status animals exhibit expression patterns
typical of older individuals? Second, is the relationship between the gene regulatory signature of social stress
and the gene regulatory signature of aging exacerbated by environmental challenge with aging-relevant
environmental stimuli? Third, does social stress induce increased cell-to-cell variance in gene expression levels,
either at baseline or in an immune challenged state, consistent with recently reported increased variance during
aging? To address these questions, the proposed study will take advantage of a powerful model for studying the
causal effects of social status: experimental manipulation of dominance rank in adult female rhesus macaques,
where earlier introduction into newly formed social groups predicts higher social status. It will draw on both cross-
sectional and longitudinal samples from 50 animals in 10 social groups, allowing us to ask whether the alleviation
of social stress also alters gene expression signatures of aging.
 Together, the proposed analysis will provide valuable insight into whether, when, and to what degree
social stress recapitulates, and potentially accelerates, aging at the gene regulatory level. Notably, rhesus
macaques are not only excellent translational models for human social stress, but also the most intensively
studied primate model for environmental effects on human aging. The results of this project will therefore have
direct translational value for understanding the risks that chronic social stress pose to healthy aging, including
environmental factors that exacerbate or ameliorate these risks.

## Key facts

- **NIH application ID:** 9792237
- **Project number:** 5F32AG062120-02
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Noah Simons
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $64,926
- **Award type:** 5
- **Project period:** 2018-12-01 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9792237

## Citation

> US National Institutes of Health, RePORTER application 9792237, Quantifying the genomic consequences of chronic social stress for accelerated aging (5F32AG062120-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9792237. Licensed CC0.

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