# Common Post-Infectious Premature Epigenetic Aging

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2024 · $614,367

## Abstract

Project Summary:
 Last year in the United States, there were 1.3 million cases of pneumonia (excluding
covid19). Worldwide, last year, there were 49 million cases respectively. Even after successful
therapy, pneumonia and other severe infections are associated with >3-fold increased mortality
risk due to increased cardiovascular disease, cancer, and recurrent infections.
 Preliminary evidence by our group and others have demonstrated that these severe
infections induce detrimental premature epigenetic scars that accelerate age-associated
epigenetic perturbations and induce pathologic inflammation and decrease immune
responsiveness. While other studies have identified post-infectious premature aging, this study
will be the first to identify which post-infectious premature aging epigenetic scars are associated
with post-infectious mortality, inflammation and decreased immune responsiveness.
 We previously identified that post-infectious detrimental epigenetic scars last at least 6
months. Studies with longer-term follow up have confirmed these epigenetic scars are still
present 82 weeks after resolution of the original insult. Therefore, we will follow participants with
severe pneumonia for 24-months after completion of successful therapy and make use of
cutting-edge single cell sequencing to clarify how these detrimental scars are persistently
propagated.
 Our preliminary in vitro data demonstrates that infection induced premature epigenetic
aging and immune perturbations can be mitigated by drugs that inhibit the TCA cycle such as
metformin, everolimus, and metformin. This study will implement mechanistic studies to explore
how inhibitors of the TCA can be used to alleviate post-infectious premature epigenetic scars
and restore immune responsiveness.

## Key facts

- **NIH application ID:** 10899585
- **Project number:** 5R01AG078268-02
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Andrew R DiNardo
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $614,367
- **Award type:** 5
- **Project period:** 2023-08-15 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10899585

## Citation

> US National Institutes of Health, RePORTER application 10899585, Common Post-Infectious Premature Epigenetic Aging (5R01AG078268-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10899585. Licensed CC0.

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