# Determining how the epigenome serves as the interface between exercise and facilitated memory formation in the adult and aging female and male brain

> **NIH NIH F32** · UNIVERSITY OF CALIFORNIA-IRVINE · 2021 · $66,390

## Abstract

Project Summary/Abstract
Normal aging is accompanied by a decline in the capability to learn, form new memories and to retrieve
previously established ones. Given a steady increase in life expectancy in the United States, where 16% of the
population consists of adults over the age of 65, the need for understanding the mechanisms by which behavioral
interventions prevent cognitive decline or impairment in both normal aging individuals in addition to those with
Alzheimer’s Disease (AD) are dire. As observed from our lab and others, hippocampus-dependent learning is
facilitated by exercise in situations that are usually subthreshold for encoding and memory consolidation and
requires the induction of brain-derived neurotrophic factor (BDNF). Previous exercise experience enables a
short, subthreshold exercise session, to again induce hippocampal BDNF in male mice, supporting the idea of a
‘molecular memory window’ for the previous exercise that facilitates later learning and memory consolidation.
Preliminary data in this proposal reveals that initial exercise establishes a ‘molecular memory window’, enabling
a short, subthreshold exercise session to facilitate learning and formation of long-term memory in situations
usually subthreshold for encoding in adult (3-month old) male mice. In a separate group of male mice, short,
subthreshold exercise also facilitated synaptic plasticity in the hippocampus, including the regulation of synaptic
structure and function genes only in mice with prior exercise experience. The epigenome is able to incorporate
prior experience (e.g. exercise) to form stable changes in cellular function, resulting in long-lasting behavioral
adaptations. Therefore, this proposal is focused on the concept that the epigenome serves as the interface
between exercise and facilitated memory formation in the adult and aging female and male brain. The overall
hypothesis is that exercise creates a ‘molecular memory’ which is encoded via epigenetic mechanisms, allowing
for facilitated long-term memory formation and synaptic plasticity in the adult and aging female and male brain.
Specific aims within this proposal will investigate the following in adult and aging females and males: Aim 1,
determine exercise parameters that establish ‘molecular memory windows’; Aim 2, examine the impact of
exercise on synaptic plasticity; and Aim 3, Identify the gene expression networks and determine the epigenetic
signature of the ‘molecular memory window’ for exercise. Given that age is the strongest risk factor for
Alzheimer’s Disease, our ability to use a novel approach and identify the epigenetic mechanisms underlying the
capability of exercise to facilitate memory function will fundamentally impact all aging individuals of both sexes
in the treatment and prevention of age-related cognitive decline or impairment. This training fellowship will allow
for development of molecular, physiology, and bioinformatics expertise. With the guidance of both Dr. Wood an...

## Key facts

- **NIH application ID:** 10233702
- **Project number:** 1F32AG071209-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Ashley A Keiser
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $66,390
- **Award type:** 1
- **Project period:** 2021-06-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10233702

## Citation

> US National Institutes of Health, RePORTER application 10233702, Determining how the epigenome serves as the interface between exercise and facilitated memory formation in the adult and aging female and male brain (1F32AG071209-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10233702. Licensed CC0.

---

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