# The effects of time restricted feeding on AGE-RAGE signaling in women at high risk for breast cancer

> **NIH NIH R21** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2021 · $57,525

## Abstract

Pre-diabetes is associated with increased breast cancer risk. Recent studies have recognized a role for
intermittent fasting, in the form of early time restricted feeding (TRF), in avoiding circadian de-synchrony to
improve insulin resistance. TRF is an eating pattern that prolongs the overnight fasting duration by coordinating
caloric intake with light-dark circadian rhythm. Prolonged nighttime fasting duration may be associated with
reduced breast cancer and recurrence risk. The underlying mechanistic aspects of prolonged overnight fasting
duration and relationship to breast cancer risk is not yet known.
Advanced glycation end products (AGEs) are reactive metabolites that accumulate in tissues as we grow older.
We now consume copious amounts of AGEs as part of the modern diet. The pathogenic effects of AGEs
contribute to insulin resistance, diabetes and cancer through the aberrant activation of stress response
pathways. A high impact finding of our animal studies is that dietary-AGE induced increases in breast tumor
growth are restricted by TRF. Dietary-AGE mediated increases in breast tumor growth were dependent upon the
stromal expression of the transmembrane receptor for AGE (RAGE). Soluble RAGE (sRAGE) is a broad term
used to define various truncated forms of full length RAGE that are found in the circulation. It encompasses a
group of tumor suppressive variants of the oncogenic full RAGE, thought to sequester AGE in the circulation by
acting as a decoy receptor. Accompanying the TRF mediated decreases in dietary-AGE induced tumor growth
was a significant increase in sRAGE.
We hypothesize that TRF induced increases in sRAGE may represent a cancer risk modification by reducing
AGE-RAGE toxicity in patients with pre-diabetes. The objective of this study is to assess the impact of TRF on
AGE-RAGE toxicity in women at higher risk of breast cancer, and explore the mechanistic implications of TRF
induced sRAGE in dietary-AGE mouse tumor models. We propose two specific aims; To conduct a pilot
Randomized Controlled Trial (RCT) designed to measure the effect of TRF on AGE-RAGE toxicity in
postmenopausal women with pre-diabetes (SA1) and to examine the mechanism of sRAGE upregulation in
response to TRF in vivo (SA2).
It is essential to identify disease risk factors in order to modify therapies aimed at decreasing breast cancer risk
in vulnerable populations. sRAGE has been identified as clinically important in diabetes and breast cancer. As
the epidemic of diabetes continues to expand, increasing the number of women at high risk of breast cancer,
identifying the mechanism and type of sRAGE increased in response to TRF will provide a platform for larger
intervention studies. Such studies would be aimed at further defining the potential of targeting environmental
AGE as a cancer prevention strategy through fasting.

## Key facts

- **NIH application ID:** 10304658
- **Project number:** 1R21CA258139-01A1
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** Victoria Jane Findlay
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $57,525
- **Award type:** 1
- **Project period:** 2021-09-10 → 2022-04-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10304658

## Citation

> US National Institutes of Health, RePORTER application 10304658, The effects of time restricted feeding on AGE-RAGE signaling in women at high risk for breast cancer (1R21CA258139-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10304658. Licensed CC0.

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