# FOXO3 Genotype, InflammAging, Cardiovascular Disease, and Dementia. Kuakini Hawaii Lifespan Study III. Administrative Supplement.

> **NIH NIH R01** · KUAKINI MEDICAL CENTER · 2022 · $421,229

## Abstract

Project Summary
This is a supplement to the parent R01 award 5R01AG027060-12: FOXO3 Genotype,
InflammAging, Cardiovascular Disease, and Dementia. Kuakini Hawaii Lifespan Study III. The
parent R01 study proposed to utilize the Kuakini Honolulu Heart Program/Kuakini Honolulu-Asia
Aging Study (Kuakini HHP/Kuakini HAAS) cohort. The Kuakini HHP study began in 1965. AIM 1.
CONDUCT a prospective study of FOXO3 genotype on incident disease and mortality utilizing 47
years of follow-up data. Hypothesis: FOXO3 enhances longevity over the adult lifespan principally
through protection against vascular disease. AIM 2. TEST whether carriers of the longevity-
associated FOXO3 allele have a protective anti-inflammatory serum profile. Hypothesis: FOXO3
reduces mortality through a cytokine-mediated anti-inflammatory pathway. AIM 3. TEST whether
FOXO3 genotype influences cognitive aging and dementia. Hypothesis: Gene variants that
promote longevity may also promote healthy brain aging, including better cognitive function, less
brain pathology on autopsy and lower rates of incident AD and VCID. Inflammation may be a
mediating factor. The parent award was in response to PA-16-160: Research Project Grant (Parent
R01). As such, the focus was not on new data collection.
Due to COVID-19 we had a number of delays in completing the primary Aims. For example, we
had limited access to our medical center, which was in lock-down, we had supply chain
disruptions, including delays in obtaining replacements for broken equipment, and inability to
receive cytokine assay supplies in a timely manner. The AIM of this supplement is to complete the
work that was disrupted due to COVID-19 issues and to measure an additional 600 study subjects
(stored blood) for blood cytokine levels. The additional 600 study subjects will provide greater power
to detect potentially statistically significant relations from currently underpowered borderline results.
This supplement addresses the need to urgently examine scientific challenges surrounding healthy
human aging, particularly with regard to inflammaging, a major driver of aging-related disease and
disability.

## Key facts

- **NIH application ID:** 10622336
- **Project number:** 3R01AG027060-12S1
- **Recipient organization:** KUAKINI MEDICAL CENTER
- **Principal Investigator:** BRADLEY JOHN WILLCOX
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $421,229
- **Award type:** 3
- **Project period:** 2005-09-30 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10622336

## Citation

> US National Institutes of Health, RePORTER application 10622336, FOXO3 Genotype, InflammAging, Cardiovascular Disease, and Dementia. Kuakini Hawaii Lifespan Study III. Administrative Supplement. (3R01AG027060-12S1). Retrieved via AI Analytics 2026-06-08 from https://api.ai-analytics.org/grant/nih/10622336. Licensed CC0.

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