# Identifying potentially modifiable exposures to improve telomere health and disease outcomes

> **NIH NIH R21** · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · 2021 · $140,232

## Abstract

Project Summary/Abstract
Telomere attrition is a key aging hallmark. Telomeres are repetitive sequences of
TTAGGG at the ends of chromosomes, shortening with age, and cells enter
senescence states when telomeres reach a critically short length. Observational and
genetic studies have shown that shorter telomere length (TL) in blood is associated with
increased risk of Alzheimer’s disease (AD). However, the study sample sizes have been
relatively small, with a 2016 meta-analysis including only 860 AD patients and 2,022
controls from 13 studies. There is increasing evidence that brain changes take place
years before Alzheimer’s disease or its related dementias (AD/ADRD) are diagnosed.
While the relationship between TL and AD/ADRD is possibly causal, associations
between TL and cognitive function or decline are inconsistent and studies to test TL
associations with brain imaging features are largely missing. To fill these gaps, we
propose to use already available brain Magnetic Resonance Imaging (MRI) data from
100,000 participants in the UK Biobank building on our parent grant (R21NR018963-
01A1). We aim to test and characterize the relationship between TL and AD/ADRD and
related measures with a much larger sample size than that of any previous study. We
will conduct association and causation analyses on TL and cognitive function as well as
brain imaging measures, using both cross-sectional and longitudinal data. The parent
grant is not focused on AD/ADRD and aims mainly to delineate modifiable exposures
that directly influence or moderate TL, and how the relationships influence health and
risk of disease. The applicant group have extensive experience undertaking aging
oriented analyses in UK Biobank (UKB), including the brain MRI data. Additionally, we
include Drs. David Steffens and Lihong Wang to support the aims of this supplement.
Dr. Steffens is a psychiatrist and his expertise has been the characterization of mood
and cognitive outcomes in late life depression, as well as the neural basis and
outcomes of AD/ADRD. Dr. Wang is a neurologist and she has conducted neuroimaging
research in patients with late-life depression and cognitive decline. Both are familiar with
UKB dementia and imaging data. We expect to gain insight into the relationship
between TL and AD/ADRD via intermediate cognitive function and brain imaging
measures. Our findings will suggest brain regions to target to slow the progression
towards AD/ADRD.

## Key facts

- **NIH application ID:** 10288463
- **Project number:** 3R21NR018963-01A1S1
- **Recipient organization:** UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
- **Principal Investigator:** Chia-Ling Kuo
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $140,232
- **Award type:** 3
- **Project period:** 2020-09-02 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10288463

## Citation

> US National Institutes of Health, RePORTER application 10288463, Identifying potentially modifiable exposures to improve telomere health and disease outcomes (3R21NR018963-01A1S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10288463. Licensed CC0.

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