# Age-Related Differences in Response to Radiation and Medical Countermeasures

> **NIH NIH UH3** · INDIANA UNIVERSITY INDIANAPOLIS · 2020 · $131,435

## Abstract

Relevant and predictive animal models are important to the study of human disease and response to
therapy. Models that employ only young animals may not be representative of the response of older/aged
human populations. The growing threat of terrorist events involving radiation, as well as the potential for
radiation accidents, underscores the need for effective medical countermeasures (MCM) against radiation.
Animal models in the geriatric population are lacking due to the high cost of aging the animals. It is becoming
increasingly clear that models of the hematopoietic acute radiation syndrome (H-ARS) in young adult animals
are not adequate representations of aged populations, since older animals (and humans) are likely to react
differently due to age-related changes in radiosensitivity, organ sensitivities, drug sensitivity, or gender
responses. The general causes of aging have been hypothesized to result from the progressive chronic
accumulation of cellular damage and the diminished capacity to maintain homeostasis and regenerative
potential.
 This proposal brings together uniquely qualified investigators who have collaborated for several years on
radiation effects on hematopoiesis and aging with current funding to evaluate radiomitigation and aging
biology. Dr. Orschell is a radiobiologist and experimental hematologist who developed and validated novel
murine models of H-ARS in young adult mice and has now developed a geriatric H-ARS model. Dr. Pelus is a
leader in stem cell biology and the effects of stress on blood stem cells. The PIs bring complimentary expertise
in radiobiology, stem cell biology, aging, as well as novel and developed animal models of adult and geriatric
H-ARS with state of the art experimental platforms.
 The PIs will test the hypothesis that advanced age impacts experimental outcome and response to therapy in
animal models of H-ARS. The PIs have documented age- and gender-related differences in the response of
young and geriatric mice to radiation, and lack of efficacy in geriatric mice of the only class of MCM thus far
approved for treatment of H-ARS. They will build upon these findings and investigate MCM with different
mechanisms of action, namely dmPGE2, lisinopril, and ciprofloxacin. In Aim 2, parameters of hematopoietic
recovery will be investigated kinetically in the H-ARS model, specifically: changes in hematopoietic
stem/progenitor and stromal cell supportive populations, DNA repair, and cell death/destruction pathways.
These results will identify age- and gender-related differences in pathway(s), cell populations, and function
between young and aged populations in response to radiation exposure that may predict or explain altered
responsiveness to MCMs, as well as identify targets that may enhance efficacy in victims of all ages, especially
the elderly. The team is uniquely positioned to evaluate the effects of age on outcomes and response to
therapy.

## Key facts

- **NIH application ID:** 10000012
- **Project number:** 5UH3AI128894-05
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** CHRISTIE M Orschell
- **Activity code:** UH3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $131,435
- **Award type:** 5
- **Project period:** 2016-09-23 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10000012

## Citation

> US National Institutes of Health, RePORTER application 10000012, Age-Related Differences in Response to Radiation and Medical Countermeasures (5UH3AI128894-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10000012. Licensed CC0.

---

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