# Viral burden and systemic inflammation as biomarkers for chronic disease and frailty in aging

> **NIH NIH U01** · INDIANA UNIVERSITY INDIANAPOLIS · 2022 · $649,153

## Abstract

Abstract
 According to the US Census Bureau there were 47.8 million people older than 65 living in the U.S. in
2015 and is projected to more than double by 2050. The implications on health care costs are substantial.
Identifying members of the aging population at increased risk for disease and frailty is a major public health
imperative. Frailty and many of the chronic diseases of aging coincide with chronic inflammation. The cause
of chronic inflammation is not known. One potential etiology is lifelong stimulation of the immune system by
acute and chronic infections. Chronic antigenic stimulation can lead to a state of “immunosenescence”, which
is associated with chronic secretion of inflammatory mediators. Persistent viruses, by virtue of their ability to
establish latency, are ideally poised to drive chronic antigenic stimulation. In this project we hypothesize that
older adults will exhibit higher viral burden that will lead to increased immune stimulation and chronic
inflammation, and that this burden will be able to predict propensity for and timing of frailty and age-
related diseases. To address this hypothesis we will measure viral burden in the blood and link it to
inflammatory gene expression profiling and markers of T cell activation/senescence to validate these as
"biomarkers" for prediction of chronic disease and frailty. This will be done through two large aging cohorts
which are collecting blood along with extensive questionnaires and tests to assess the presence of chronic
diseases and frailty. We propose the following specific aims: (1) To measure the blood virome (including
bacteriophages) in an elderly population and younger controls. We will determine the presence of RNA
and DNA viruses as well as bacteriophages in the blood compartment of younger and older adults using
shotgun sequencing and RNA-Seq. The presence and activity of cytomegalovirus as a potential driver of
immune aging will be assessed by monitoring anti-CMV immune responses. (2) To assess markers of
chronic inflammation in an elderly population and younger controls and correlate these with evidence
of immune aging and viral specific immune responses. We will determine the degree of systemic
inflammation in the blood of subjects through measurement of cytokines and gene expression profiling of
PBMCs. We will assess the degree of lymphocyte activation, senescence, and virus-specific activity by flow
cytometry. (3) To correlate the blood virome, evidence of systemic inflammation and the presence of
chronic disease and frailty in test subjects and create a potential inflammatory and viral “biomarker”
for the detection of the complications of aging. Using data from specific aims 1 and 2, we will connect viral
burden (including bacteriophages) and markers of chronic inflammation to each other and to clinical outcomes
in a cross-sectional and mixed cross-sectional/longitudinal manner. This interdisciplinary project should not
only deliver biomarkers for the complicati...

## Key facts

- **NIH application ID:** 10412933
- **Project number:** 5U01AG060900-05
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** JANKO Z. NIKOLICH
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $649,153
- **Award type:** 5
- **Project period:** 2018-09-30 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10412933

## Citation

> US National Institutes of Health, RePORTER application 10412933, Viral burden and systemic inflammation as biomarkers for chronic disease and frailty in aging (5U01AG060900-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10412933. Licensed CC0.

---

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