# Integrative multi-omic investigation of age-related changes in trabecular bone

> **NIH NIH K01** · WAKE FOREST UNIVERSITY HEALTH SCIENCES · 2021 · $33,242

## Abstract

The ultimate goal of this project is to identify age-related changes in bone in the context of other metabolically
active tissues. Age-related decline in bone strength increases risk of fractures which occur in 1 in 2 American
women and 1 in 4 American men after age 45. Our current methods of identifying individuals at risk of fracture
rely on bone mineral density. However, 85% of individuals with a fracture do not have bone mineral density low
enough to be clinically diagnosed with osteoporosis so other contributors to age-related bone fracture risk must
be identified and targeted with new treatment options. This project examines age-related differences in DNA
sequence, gene expression (“transcriptomics”), and protein expression (“proteomics”) of trabecular bone in
baboons to test the hypothesis that an integrated “omics” approach will identify more dysregulated pathways in
elderly individuals than individual analyses alone. Because of its strong similarity to humans in bone turnover,
age-related decline, and metabolism, the baboon will be used as a model for human bone aging.
Aim 1: Identify changes in protein interaction networks associated with transition out of middle-age bone
homeostasis to elderly bone decline. Network analyses will identify pathways that change with age and by sex.
Aim 2: Evaluate utility of multi-omic integration of genomic, transcriptomic, and proteomic data in describing
biological changes in bone driven by aging. Integrated analyses will differentiate between network dysregulation
arising from simultaneous age-related changes at multiple levels of cellular organization or inter-regulation
among the levels versus pathologies rooted solely in proteomic variation. Aim 3: Differentiate between age-
related changes in integrated biological pathways occurring within the musculoskeletal system versus those
occurring more broadly. Differentially integrated omic pathways between middle-aged and older animals will be
compared between bone and skeletal muscle, which are functionally integrated, and between bone and liver,
which are both metabolically responsive tissues.
Through the accomplishment of these significant aims, this project will train the PI in a new areas of omic analysis
(proteomics) which she will integrate with previous experience in the statistical analysis of genomic,
transcriptomic, and epigenomic data. This training will including coursework in aging biology and workshops in
proteomic, metabolomic, and integrative omics analysis plus extended hands-on training under the direction of
her mentors. Demand for these types of integrative omics skills is increasing in our current “big data” era. The
PI will develop the skills and preliminary data necessary to compete for independent NIH funding to study the
biology of bone aging in the context of the metabolic syndrome. Ultimately, this will lead to the success of her
long term goal of utilizing multi-omic technologies to identify the earliest declines in bone heal...

## Key facts

- **NIH application ID:** 10385127
- **Project number:** 3K01AG056663-03S1
- **Recipient organization:** WAKE FOREST UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Ellen Elizabeth Quillen
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $33,242
- **Award type:** 3
- **Project period:** 2020-06-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10385127

## Citation

> US National Institutes of Health, RePORTER application 10385127, Integrative multi-omic investigation of age-related changes in trabecular bone (3K01AG056663-03S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10385127. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*