# Validation of Nuclear Morphology as a Biomarker of Aging and Aging-Related Phenotypes

> **NIH NIH U01** · JOHNS HOPKINS UNIVERSITY · 2020 · $603,574

## Abstract

Abstract
Alterations in the nuclear protein lamin and associated structures in the nucleus have been
identified as a source of nuclear morphology changes that markedly impact overall cellular
function. These changes in nuclear morphology are thought to drive molecular changes that
influence a wide range of aging-related phenotypes and chronic disease states. Importantly, we
have recently used high-throughput measurements of nuclear morphology to identify outstanding
biomarkers of chronological age. We hypothesize that these age-related changes in nuclear
morphology are highly correlated with chronological age in healthy individuals, and that a specific
age-related biological change in lamin underlies this phenomenon. Building on our prior
development of these high-throughput and accurate measures of nuclear morphology, we propose
here to further develop this biological discovery and technology as a valid and reliable biomarker
of aging-related biological mechanisms. We hypothesize that changes in nuclear morphology can
be rapidly measured and that age-related alterations correlate with aging-related phenotypes and
disease states independently of chronological age, consistent with a measure of cellular biological
age. To test these hypotheses and move results toward clinical utility, we have assembled a highly
synergistic, interdisciplinary team propose the following specific aims:
Aim 1. Using our validated single-cell technologies, we will develop a mechanistic understanding
of how descriptors of nuclear morphology in human dermal fibroblasts and B-lymphocytes are
robust biomarkers of aging in healthy individuals. Aim 2. Establish the accuracy and precision
with which our proposed biomarkers identify chronological age for individuals with varying
demographic, behavioral, and health characteristics. Aim 3. We will examine the strength with
which morphological biomarkers discriminate individuals with adverse phenotypes and outcomes
of aging, and at risk for the development of these, from healthy older adults, above and beyond
chronological age.

## Key facts

- **NIH application ID:** 9952304
- **Project number:** 5U01AG060903-03
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Denis Wirtz
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $603,574
- **Award type:** 5
- **Project period:** 2018-09-30 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9952304

## Citation

> US National Institutes of Health, RePORTER application 9952304, Validation of Nuclear Morphology as a Biomarker of Aging and Aging-Related Phenotypes (5U01AG060903-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9952304. Licensed CC0.

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