# Effects of 12-weeks of High-intensity Resistance Aerobic Circuit Exercise Training on Epigenetic Aging and Inflammation in Older HIV-infected Veterans

> **NIH VA I01** · SALEM VA MEDICAL CENTER · 2020 · —

## Abstract

The Veterans Health Administration (VHA) is the largest U.S. HIV health provider with 64% of these
Veterans 50+ years of age. HIV infection in the setting of antiretroviral therapy represents a chronic disease
with an advanced aging phenotype manifested as increased cardiovascular disease, sarcopenia, and frailty,
primarily driven by systemic inflammation. We found a 42% reduction in VO2peak in older HIV+ adults that
significantly improved with high-intensity aerobic (AEX) and resistance training (RT). Yet, durable strategies for
high-intensity exercise in older adults remain a challenge and limited data are available in older HIV+ adults.
There is an urgent need to address these knowledge gaps in order to prevent widespread disability in HIV+
Veterans. Our objective is to provide a high-intensity exercise program for older Veterans that can be widely
disseminated and attenuates processes underlying aging. Epigenetic changes with increased age encapsulate
the putative effects of biological aging and lifestyle factors. DNA methylation (DNAm) patterns are frequently
modified in genes encoding pro-inflammatory cytokines, but can be reversed with exercise training. DNA
methylation age (DNAm Age) is an epigenetic biomarker that is expressed in years and provides a concrete
benchmark of advanced aging. We found that HIV+ adults have DNAm Age 11 years greater than age-
matched adults without HIV. Further, in adults without HIV, increased DNAm Age is associated with physical
inactivity, weakness and frailty. Our preliminary data in the Veterans Aging Cohort Study (VACS) show that
DNAm Age correlates with the VACS Index, a measure of frailty in HIV+ adults. However, the impact of
exercise training on DNAm Age has yet to be determined in any patient population. We propose to adapt our
center-based high-intensity AEX+RT intervention in older HIV+ Veterans into a video telehealth (VTEL)
delivered functional (no stationary equipment) exercise program that leverages epigenetic outcomes to
demonstrate anti-aging effects of exercise. The overarching hypothesis is that VTEL high-intensity
functional circuit exercise in older HIV+ Veterans will improve the advanced aging phenotype and
attenuate DNAm epigenetic processes underlying aging. Our experimental approach includes a 12-week
VTEL exercise intervention in 80 older HIV+ Veterans who are randomized to exercise or standard of care
sedentary control groups. AIM 1 will determine the effect of VTEL exercise on VO2peak, sarcopenia, and frailty
as phenotypic outcomes of advanced aging in HIV. AIM 2 will investigate the effect of VTEL exercise on DNAm
Age as a biomarker of advanced aging. AIM 3 will determine the effect of VTEL exercise on DNA methylation
of specific genes encoding specific pro-inflammatory cytokines in leukocytes. This approach will advance our
understanding of effective and feasible exercise strategies to prevent and minimize disability in patient
populations with advanced aging. Findings will prov...

## Key facts

- **NIH application ID:** 9836352
- **Project number:** 1I01RX002790-01A2
- **Recipient organization:** SALEM VA MEDICAL CENTER
- **Principal Investigator:** Vincent Charles Marconi
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2019-10-01 → 2023-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9836352

## Citation

> US National Institutes of Health, RePORTER application 9836352, Effects of 12-weeks of High-intensity Resistance Aerobic Circuit Exercise Training on Epigenetic Aging and Inflammation in Older HIV-infected Veterans (1I01RX002790-01A2). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9836352. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*