Item Details

title

INTEGRATIVE MULTI-OMICS ANALYSIS OF AGE-ASSOCIATED GAIT SPEED DECLINE IN VERVET SKELETAL MUSCLE

author

Rudasi, Eleanor

abstract

Skeletal muscle aging, characterized by the progressive loss of mass and function known as sarcopenia, significantly contributes to frailty, morbidity, and reduced quality of life in the elderly. The complex, multifactorial nature of muscle aging, involving processes like inflammaging, mitochondrial dysfunction, and altered proteostasis, has hampered the development of effective therapies. A systems-level understanding integrating multiple layers of biological regulation is needed to decipher the mechanisms driving sarcopenia. This thesis aimed to identify coordinated age-associated molecular changes in non-human primate skeletal muscle using an integrative multi-omics approach. We analyzed bulk vastus lateralis muscle tissue from 28 vervet monkeys(Chlorocebus aethiops sabaeus) spanning a wide age range. Transcriptomic (mRNA), epigenomic (DNA methylation), and post-transcriptional (microRNA) data were generated and integrated using the MixOmics DIABLO framework. The analysis identified specific mRNAs, DNA methylation sites, and miRNAs significantly associated with age. Furthermore, the integrative approach revealed correlated multi-omics features and biological pathways perturbed during muscle aging, highlighting potential regulatory networks involving epigenetic, transcriptional, and post-transcriptional crosstalk. These findings provide novel insights into the molecular landscape of skeletal muscle aging in a relevant primate model, generating hypotheses about the interplay of regulatory mechanisms contributing to sarcopenia. This systems-level characterization offers potential avenues for future mechanistic studies and the identification of therapeutic targets to promote healthy muscle aging.

subject

African Green Monkeys

MixOmics DIABLO

mRNA miRNA mDNA

Non-Human Primates

transcriptome miRNome methylome

Vastus lateralis Skeletal Muscle Functional Decline

contributor

Quillen, Ellen E. (advisor)

Zimmerman, Kip D. (committee member)

date

2025-06-24T08:36:44Z (accessioned)

2025 (issued)

degree

Biomedical Science Research – MS (discipline)

embargo

2026-06-23 (terms)

2026-06-23 (liftdate)

identifier

http://hdl.handle.net/10339/111065 (uri)

language

en (iso)

publisher

Wake Forest University

type

Thesis