# Optimizing Keratinocyte Calcium Signaling Enhances Differentiation in Aged Epidermis

> **NIH VA I01** · VETERANS AFFAIRS MED CTR SAN FRANCISCO · 2024 · —

## Abstract

Aged epidermis shows progressive defects in proliferation, differentiation and barrier formation, manifesting as
eczematous dermatoses, xerosis, itch and increased susceptibility to contact dermatitis and infections.
Previously, we found that defects in epidermal calcium signaling, transduced through the plasma membrane
calcium receptor (CaSR), underlie intrinsic aging. In preliminary findings we show that CaSR expression
decreases in aged epidermis and CaSR agonists rescue calcium signaling, E-cadherin reorganization, growth
and migration in aged keratinocytes, epidermal equivalents and aged or CaSR-/- mice. Because burn pit
pollution also causes premature skin aging (extrinsic skin aging) and is a focus of veteran health, we propose
to determine what age-related transcriptional or epigenetic mechanisms drive intrinsic vs. extrinsic aging. We
next will assess how increasing CaSR expression or function, using exogenous vitamin D or CaSR agonists,
rescue intrinsic or extrinsic age-related epidermal defects. Finally, we will use these results to develop
therapeutic approaches that ameliorate calcium signaling and differentiation/barrier defects in intrinsically aged
mice or mice whose skin is prematurely aged due to particulate pollution.
The overall hypothesis of this project is that the age-related decreases in calcium signaling dysregulate
intrinsic and extrinsic keratinocyte differentiation and barrier homeostasis.
The overall goal of this project is to normalize age-related epidermal defects by enhancing calcium signaling
and CaSR expression/function.

## Key facts

- **NIH application ID:** 10700473
- **Project number:** 1I01BX006094-01A1
- **Recipient organization:** VETERANS AFFAIRS MED CTR SAN FRANCISCO
- **Principal Investigator:** Theodora M Mauro
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2023-10-01 → 2027-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10700473

## Citation

> US National Institutes of Health, RePORTER application 10700473, Optimizing Keratinocyte Calcium Signaling Enhances Differentiation in Aged Epidermis (1I01BX006094-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10700473. Licensed CC0.

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