# Understanding the effect of aging on cancer incidence

> **NIH NIH R36** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2020 · $76,817

## Abstract

PROJECT SUMMARY
In breast cancer, the median age of diagnose is 61 year old and the incidence then declines in elderly women.
However, very few studies focus on the effect of age-related changes on tumorigenesis in the aged breast and
almost all experimental models use young mice (3 months). Therefore there is a need to develop mouse
models that best reflect the incidence of the disease in humans using aged rather than young or elderly mice.
In order to begin characterizing the effect of aging in mammary tumorigenesis, we performed preliminary
studies in an inducible mammary tumor model, in which all variables are identical except for age. After
oncogene induction, we found that aged (18 months = 61 years in humans) mice have increased tumor
incidence, compared to young (3 months) mice. In addition, tumors from aged mice express a unique genetic
signature, compared to tumors from young mice. In contrast the increased tumor growth in vivo, aged
mammary epithelial cells induced ex vivo formed smaller colonies compared to induced young mammary
epithelial cells. Furthermore, our preliminary studies also suggest that the aged mammary gland is
characterized by a decrease in collagen abundance and disorganized fiber orientation. Based on these
findings, we propose to further analyze age-related alterations in both normal and tumor mammary cells, and
microenvironment architecture (collagen abundance and orientation). In Aim 1, we will assess cell-intrinsic
age-related changes in tumors arising from aged mice. We will perform transcriptome analysis of tumor cells
arising from young and old females in two mouse mammary tumor models, MMTV-rtTA/TetO-ErbB2 and
MMTV-rtTA/TetO-Ras. To identify potential novel targets in tumors arising from aged mice, we will compare
the young and aged tumor signatures with young and old normal mammary epithelial cells. In Aim 2, we will
investigate the cell-extrinsic effect of age-related changes in collagen composition on mammary tumor growth.
First, we will further characterize the age-related changes in collagen abundance and orientation young and
aged normal mammary glands using second harmonic generation imaging. We will also establish a 3D culture
method using decellularized mammary glands from young and aged mice to study the effect of biological aging
on tumor cell growth in vitro. We will confirm our studies in a series of swapping experiments using establish
young and aged syngeneic cohorts. The purpose of the proposed studies is to improve our understanding of
how age-related changes in the mammary gland contribute to breast cancer risk, and may identify new targets
for breast cancer treatment in older women.

## Key facts

- **NIH application ID:** 10043596
- **Project number:** 1R36AG068233-01
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Maria Lucia Gomez
- **Activity code:** R36 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $76,817
- **Award type:** 1
- **Project period:** 2020-09-01 → 2020-11-03

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10043596

## Citation

> US National Institutes of Health, RePORTER application 10043596, Understanding the effect of aging on cancer incidence (1R36AG068233-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10043596. Licensed CC0.

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