Skeletal Muscle Proteome Differs Between Young and Targeted Replacement Mice in a Sex-dependent Manner

Overview

Journal Front Aging Neurosci

Specialty Geriatrics

Date 2024 Dec 5

PMID 39634654

Authors

Chelsea N Johnson

Colton R Lysaker

Colin S McCoin

Mara R Evans

John P Thyfault

Heather M Wilkins

Jill K Morris

Paige C Geiger

Affiliations

Soon will be listed here.

Abstract

Introduction: Apolipoprotein E4 () is the strongest genetic risk factor for Alzheimer's disease (AD), yet it's unclear how this allele mediates risk. carriers experience reduced mobility and faster decline in muscle strength, suggesting skeletal muscle involvement. Mitochondria are critical for muscle function and although we have reported defects in muscle mitochondrial respiration during early cognitive decline, -mediated effects on muscle mitochondria are unknown.

Methods: Here, we sought to determine the impact of on skeletal muscle bioenergetics using young, male and female (control) and targeted replacement mice ( = 8 per genotype/sex combination). We examined the proteome, mitochondrial respiration, fiber size, and fiber-type distribution in skeletal muscle.

Results: We found that alters mitochondrial pathway expression in young mouse muscle in a sex-dependent manner without affecting respiration and fiber size or composition relative to . In both sexes, the expression of mitochondrial pathways involved in electron transport, ATP synthesis, and heat production by uncoupling proteins and mitochondrial dysfunction significantly differed between and muscle. For pathways with predicted direction of activation, electron transport and oxidative phosphorylation were upregulated while mitochondrial dysfunction and sirtuin signaling were downregulated in female vs. muscle. In males, sulfur amino acid metabolism was upregulated in vs. muscle.

Discussion: This work highlights early involvement of skeletal muscle in a mouse model of -linked AD, which may contribute to AD pathogenesis or serve as a biomarker for brain health.

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