# Impact of aging on intestinal tumorigenesis

> **NIH NIH UH3** · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · 2020 · $150,000

## Abstract

Aging has a profound impact on tissue regeneration and cancer incidence. However, the mechanisms of
how aging reduces the function of stem cells, alters the transformability of stem cells to beget tumors, or
influences tumor progression are poorly understood. Although aging is the single biggest risk factor for cancer
in humans and laboratory animals, cancer has been modeled and interrogated solely in young rodent models.
Our system for addressing these questions is the mammalian intestine where a majority of intestinal stem cells
(ISCs) in the small intestine and colon express Lgr5. Our preliminary studies suggest that ISC numbers are
diminished and less proliferative in old mice and humans and that elderly ISCs are less functional in an in vitro
organoid (3-D mini-intestinal) assay of stem cell function, indicating that cell autonomous mechanisms
contribute to intestinal stem cell aging. Finally, we find that aged mice, like aged humans, develop
spontaneous intestinal adenomas and carcinoma; however, the mechanisms of how aging reduces the
function of stem cells, alters the transformability of stem cells to give rise to tumors, or influences tumor
progression/metastasis are poorly understood. In this proposal, we will study how aging influences the genesis,
progression, and treatment response of intestinal adenomas and carcinomas in inducible, genetically defined
mouse models of intestinal tumors. Specifically, we will establish aging mouse colonies to interrogate how age-
related changes in the tumorigenic potential of intestinal stem and progenitor cells contribute to enhanced
tumor incidence in old age (Aim 1); that aging has autonomous and non-autonomous effects on tumor
progression (Aim 2), and that aging alters the treatment response of intestinal tumors to chemotherapy or
radiation (Aim 3).

## Key facts

- **NIH application ID:** 10000069
- **Project number:** 5UH3CA213396-05
- **Recipient organization:** WHITEHEAD INSTITUTE FOR BIOMEDICAL RES
- **Principal Investigator:** David M. Sabatini
- **Activity code:** UH3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $150,000
- **Award type:** 5
- **Project period:** 2016-09-20 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10000069

## Citation

> US National Institutes of Health, RePORTER application 10000069, Impact of aging on intestinal tumorigenesis (5UH3CA213396-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10000069. Licensed CC0.

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