# FOXO3, Telemere Dynamics and Healthy Brain Aging

> **NIH NIH P20** · KUAKINI MEDICAL CENTER · 2022 · $163,577

## Abstract

Project Summary/Abstract 
Longevity appears to be strongly affected by genetic and cellular factors. The FOXO3 gene that encodes the 
transcription factor forkhead box O-3 (FOXO3) has been consistently linked to increased human lifespan. 
Aging is typically accompanied by gradual brain atrophy and neurocognitive decline, but the cellular 
mechanisms underlying the aging process are still unclear. 
The proposed study seeks to understand how aging at the cellular level, as characterized by telomere 
shortening and altered telomerase activity, is related to longevity and brain aging. We hypothesize that the 
protective FOXO3 gene variant is associated with decelerated brain aging, and suggest that a slower rate of 
brain aging is also linked to greater telomerase activity and telomere length in peripheral blood leukocytes 
(PBL). Brain volume and function will be cross-sectionally assessed by structural magnetic resonance imaging 
(MRI) and resting-state functional connectivity (RSFC) MRI, respectively, in 100 male and female Kuakini 
Honolulu Heart Program (Kuakini HHP) Offspring study participants. Regional brain atrophy and disrupted 
RSFC will serve as indices of brain aging and will be examined for associations with FOXO3 genotype and 
PBL telomerase activity and telomere length. Additionally, we will investigate whether differences in RSFC 
associated with FOXO3 genotype, telomerase activity or telomere length, 8-oxo-dG (a measure of DNA break 
frequency), or anti-inflammatory cytokine levels in the blood relate to cognitive processes impaired in normal 
aging. Results from this study may provide insight into effects of the protective FOXO3 variant on the rate of 
brain aging, and may elucidate biological mechanisms of aging and eventually identify interventions to increase 
the number of years of healthy living.

## Key facts

- **NIH application ID:** 10493191
- **Project number:** 5P20GM125526-04
- **Recipient organization:** KUAKINI MEDICAL CENTER
- **Principal Investigator:** Kalpana Juliet Kallianpur
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $163,577
- **Award type:** 5
- **Project period:** 2019-09-10 → 2023-02-01

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10493191

## Citation

> US National Institutes of Health, RePORTER application 10493191, FOXO3, Telemere Dynamics and Healthy Brain Aging (5P20GM125526-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10493191. Licensed CC0.

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