# Optimization and standardization of telomere length measurement by qPCR for population-based health research

> **NIH NIH U01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $322,280

## Abstract

ABSTRACT
 Aging is associated with progressive decline of physiological functions and increased risks for major
aging-related diseases. Telomere attrition has been proposed as one of the cellular mechanisms that
accompany aging and pathologies related to aging. Critically short telomere length (TL) leads to senescence
and is etiologically linked to a range of different human diseases. A growing number of biomedical,
epidemiological and population research studies have used telomere length as a biomarker of cellular aging
that reflects the cumulative effects of environmental exposures and life experiences as well as a risk factor for
major diseases.
 Of the major methods utilized to determine telomere length, quantitative PCR (qPCR) remains the most
suitable for large-scale population studies with hundreds or even thousands of samples, due to its low cost,
ease of adoption, low DNA quantity requirement and advantages for high throughput. However,
inconsistencies have been reported when qPCR TL assays were repeated for the same samples using
different pre-analytical and analytical conditions, highlighting the need for careful methodological study of each
step of this process. Sample type selection, sample collection, storage, processing issues and assay
procedures have each been identified as import steps that may contribute to assay variability. Systematic
studies of how each of these steps impacts the assay is urgently needed to reach a consensus on the best
practices for qPCR TL analysis.
 In this proposal, we plan to optimize the pre-analytical and analytical conditions for qPCR focusing on
three specimen types: whole blood, the most commonly used specimen for TL in population-based studies;
dried blood spots (DBS), a non-invasive collection method widely used to collect neonatal samples, and saliva,
another non-invasive home collection method. We further propose to create a set of fully characterized quality
control (QC) DNA samples and a reference standard genomic DNA sample, to be used as shared resources
for labs that perform qPCR TL. Finally, we propose to augment telomere length measurement by validating
assays for single nucleotide polymorphisms (SNP) associated with TL identified through prior genome-wide
association studies (GWAS) and examining whether a genetic sum score (from combining the effects of all
SNPs) is associated with longitudinal telomere length change in a pediatric cohort as well as an adult cohort.
We realize that sample collection, storage and processing conditions, as well as cross-tissue comparisons are
critical for qPCR TL and these issues are addressed by other U01 proposals and the U24 network. As a voting
member of the steering committee for the U24, we will fully participate in the U24 network by assaying samples
distributed by the U24 and the NIA intramural labs for method comparisons as directed by the committee; and
by fully adhering to guidelines and protocols established by the committee.

## Key facts

- **NIH application ID:** 10174683
- **Project number:** 5U01AG064785-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Jue Lin
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $322,280
- **Award type:** 5
- **Project period:** 2019-09-30 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10174683

## Citation

> US National Institutes of Health, RePORTER application 10174683, Optimization and standardization of telomere length measurement by qPCR for population-based health research (5U01AG064785-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10174683. Licensed CC0.

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