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Activity-based sensing reveals elevated labile copper promotes liver aging via hepatic ALDH1A1 depletion

ABSTRACT: Oxidative stress plays a key role in aging and related diseases, including neurodegeneration, cancer, and organ failure. Copper (Cu), a redox-active metal ion, generates reactive oxygen species (ROS), and its dysregulation contributes to aging. Here, we develop activity-based imaging probes for the sensitive detection of Cu(I) and show that labile hepatic Cu activity increases with age, paralleling a decline in ALDH1A1 activity, a protective hepatic enzyme. We also observe an age-related decrease in hepatic glutathione (GSH) activity through noninvasive photoacoustic imaging. Using these probes, we perform longitudinal studies in aged mice treated with ATN-224, a Cu chelator, and demonstrate that this treatment improves Cu homeostasis and preserves ALDH1A1 activity. Our findings uncover a direct link between Cu dysregulation and aging, providing insights into its role and offering a therapeutic strategy to mitigate its effects.

ORGANISM(S): Mus Musculus (mouse)

SUBMITTER: Jefferson Chan

PROVIDER: PXD059736 | JPOST Repository | Thu Jan 16 00:00:00 GMT 2025

REPOSITORIES: jPOST

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			Action	DRS
	22-048-Chan-Old-liver.raw	Raw
	22-048-Chan-Young-liver.raw	Raw
	22-150%20treat%20647-F017231.mgf	Mgf
	22-150%20treat%20648-F017233.mgf	Mgf
	22-150%20treat%20649-F017234.mgf	Mgf

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Activity-based sensing reveals elevated labile copper promotes liver aging via hepatic ALDH1A1 depletion

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