# Aging with HIV: Novel Biomarkers of Inflammation and Morbidity

> **NIH NIH K23** · WEILL MEDICAL COLL OF CORNELL UNIV · 2022 · $194,806

## Abstract

PROJECT SUMMARY/ABSTRACT
The candidate’s career goal is to become an independent physician-scientist studying HIV and aging, and the
increased burden of medical co-morbidities and geriatric syndromes in older adults with HIV (OAH). The
candidate has laid the foundation for achieving this goal by gaining clinical expertise in caring for OAH,
conducting research, and obtaining a Master’s Degree in Clinical and Translational Investigation. To achieve
her career goal, the candidate will need to expand upon her geroscience and translational research skills,
including additional biostatistics and research methods training which are described in this resubmission.
A key component of the candidate’s training will be conducting the proposed research project. Despite
effective antiretroviral medications, OAH bear a greater burden of medical co-morbidities and geriatric
syndromes than their HIV-negative peers. Translational research investigating biomarkers inflammation offers
as opportunity for insight to the process of accelerated/accentuated aging that is observed in OAH. Cell-free
mitochondrial DNA (cfmtDNA) is released from cells undergoing stress and necroptosis-mediated cell death
and has the potential to serve as a mediator and marker of chronic immune activation and dysregulation.
We hypothesize that cfmtDNA will be associated with lower cognitive performance and greater frailty in a
longitudinal study of OAH. Previously, we have studied a cohort of OAH (age 55 and over) at our institution,
and those with cognitive impairment had higher average levels of cfmtDNA in plasma than participants without
cognitive impairment. We propose to leverage this existing study to investigate the following specific aims: 1)
Determine the association between cfmtDNA and cognition in OAH; 2) Determine the association between
cfmtDNA and longitudinal physical function in OAH; and 3) Evaluate the immunostimulatory potential of
cfmtDNA from OAH with and without cognitive decline. Participants from our existing cohort will be invited
back for two study visits separated by 18-24 months, each visit will include detailed neurocognitive
assessment, physical function measures, falls and instrumental and activities of daily living, and blood and
urine specimen collection for analysis and creation of a biorepository. Together, these investigations will shed
light on the relationship between cfmtDNA, immune activation and geriatric-related syndromes in OAH.
This project proposes a five-year, multifaceted training program under the mentorship of Dr. Marshall Glesby
as the primary mentor, as well as Drs. Mary Choi, Lishomwa Ndhlovu, and Eugenia Siegler as co-mentors.
Together with a Scientific Advisory Committee, they will provide the expertise in research design, biomarkers,
immunology and geroscience that will allow support the success of this project. The completion of the
proposed project will lead to an enhanced understanding of cfmtDNA as a biomarker of geriatric syndromes i...

## Key facts

- **NIH application ID:** 10463849
- **Project number:** 5K23AG072960-02
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Carrie Down Johnston
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $194,806
- **Award type:** 5
- **Project period:** 2021-08-15 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10463849

## Citation

> US National Institutes of Health, RePORTER application 10463849, Aging with HIV: Novel Biomarkers of Inflammation and Morbidity (5K23AG072960-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10463849. Licensed CC0.

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