# GEMSSTAR PERSPIRE-COPD

> **NIH NIH R03** · DUKE UNIVERSITY · 2024 · $161,000

## Abstract

TITLE: Pulmonary Rehabilitation as a Senolytic Intervention to Reduce Exacerbations in COPD
(PERSPIRE-COPD)
PROJECT ABSTRACT
 Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are responsible for over
250,000 hospitalizations per year in older American adults (age ≥ 65). Current therapies are ineffective at
preventing AECOPD resulting in an urgent and unmet need to develop more effective treatments. A major barrier
to progress is identification of a modifiable biologic target. Among currently available treatments, pulmonary
rehabilitation (PR) is safe and effective at preventing AECOPD in older adults. However, the biological
mechanisms responsible for AECOPD prevention are not well understood. To address this gap in knowledge,
we will leverage PR as a model to identify modifiable biologic targets to prevent AECOPD. Our findings will allow
further PR optimization and provide biologic targets for future therapeutic drug development.
 Host immunity likely plays an important role in AECOPD prevention as a majority of events are caused
by respiratory viral infections. Considering this, I propose that age-related decline in immune system function
(i.e. immunosenescence) predisposes patients to higher AECOPD risk. Greater immunosenescence leads to
more AECOPD events. Immunosenescence is characterized by high levels of senescent T-cells and senescence
associated secretory phenotype (SASP). Therapies that eliminate senescent cells (i.e. senolytics) could
potentially lower AECOPD risk. Exercise interventions have been shown to remove senescent T-cells and
increase naïve T-cell proliferation. Considering PR is an exercise training intervention. I hypothesize that PR
reduces the relative frequency of senescent T-cells to naïve T-cells and SASP levels. These changes will
increase resilience to respiratory infections, lower AECOPD risk, and accelerate recovery from AECOPD. In
preparation for future investigations into AECOPD risk, we will test the hypothesis that PR is associated with a
decrease in relative frequency of senescent to naïve T-cells and SASP levels and determine the correlation of
these changes with an improvement in physical performance and HRQoL. To begin to address this line of
investigation, I’ve developed a PR biorepository that contains biospecimens collected at standardized intervals
and pre/post-PR measurements of physical performance and HRQoL.
 Completion of these aims will support my professional development towards a career as a translational
scientist with a focus in aging biology and clinical trials in older adults with COPD. The GEMSSTAR will deepen
my knowledge of SASP biomarkers, T-cell immunology, immunosenescence, and within-subjects methodology
and foster collaborations within the geriatrics research community. The project will result in 3 published
manuscripts, 2 presentations at national conferences, and preliminary data towards a subsequent K76 Paul B.
Beeson Career Development Award. Altogether, the GE...

## Key facts

- **NIH application ID:** 10917267
- **Project number:** 5R03AG082878-02
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Christopher Mosher
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $161,000
- **Award type:** 5
- **Project period:** 2023-09-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10917267

## Citation

> US National Institutes of Health, RePORTER application 10917267, GEMSSTAR PERSPIRE-COPD (5R03AG082878-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10917267. Licensed CC0.

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