# Targeting Senescence to Improve Wound Healing in Aging

> **NIH NIH K76** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2024 · $243,000

## Abstract

Impaired or delayed wound healing is a major problem affecting primarily older adults, millions of older adults in
the United States are affected per year. Delayed wound healing increases aged patients’ risk of chronic wounds,
wound infections, and tissue necrosis, resulting in significant morbidity and mortality. Wound care is also a rising
economic problem with an estimated $10 billion annually spent on wound care for older adults. The various
causes for delayed healing of aging ultimately result in perturbations of normal wound healing processes. This
includes a recently discovered wound healing response incorporating cellular senescence, a biologically active
state of permanent growth arrest caused by various stressors like tissue injury. Senescent cells (SnC) that arise
acutely in cutaneous wounds have beneficial effects in wound healing when they are transiently present,
however, specific SnC identities and their associated functions during wound healing have still not been
thoroughly characterized. My preliminary data generated during my GEMSSTAR award confirm a robust and
transient increase in beneficial senescence during excisional wound healing in young (2 month) mice, required
for timely wound resolution. However, my data also demonstrates that in aged (24 month) mice with delayed
wound healing, this acute wound senescence response is significantly attenuated. A similar diminished acute
senescence-like response occurs during aged human wound healing suggesting that attenuation is conserved
between species. To gain better understanding of wound SnCs that benefit wound healing and which are
diminished in aging, my lab has isolated high-expressing p16Ink4a (a common senescence marker) cells from
the wounds of young p16tdTom mice. Preliminary single-cell RNAseq analysis reveals multiple wound cell types
with high p16+ expression during wound healing. A majority are within distinct clusters of fibroblasts (Fb) and
macrophages (Mϕ) with p16+ expression associated with positive regulation of wound healing: p16+ wound Fbs
upregulate genes for protein synthesis and certain collagens while p16+ wound Mϕs are more anti-inflammatory
and promote extracellular matrix deposition with both cell types being more apoptosis-resistant compared to their
respective p16-negative counterparts. As transient senescence is important for optimal wound healing in
younger organisms this project’s goals are to uncover the cellular mechanisms by which specific wound SnCs
positively influence wound healing and determine their roles in delayed healing of aging. I will test the overall
hypothesis that age-related attenuation of beneficial wound SnCs contributes to delayed wound healing in aged
mammals and that restoration of these key wound SnCs can promote more timely wound resolution. The
following Aims are designed to elucidate changes in wound SnCs throughout aging, define their beneficial impact
on wound healing, and provide the therapeutic framework for treatment ...

## Key facts

- **NIH application ID:** 10909391
- **Project number:** 5K76AG083300-02
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** Daniel Sam Roh
- **Activity code:** K76 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $243,000
- **Award type:** 5
- **Project period:** 2023-09-01 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10909391

## Citation

> US National Institutes of Health, RePORTER application 10909391, Targeting Senescence to Improve Wound Healing in Aging (5K76AG083300-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10909391. Licensed CC0.

---

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