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Extracellular vesicle-encapsulated miR-30c-5p reduces aging-related liver fibrosis

Extracellular vesicle-encapsulated miR-30c-5p reduces aging-related liver fibrosis

Alice C Rodrigues ^1,2, Yujing J Heng ³, Frank J Slack ^1,3,4

Alice C Rodrigues ^1,2, Yujing J Heng ³, Frank J Slack ^1,3,4

¹Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
²Department of Pharmacology, Universidade de Sao Paulo Instituto de Ciencias Biomedicas, São Paulo, Brazil.
³Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
⁴Harvard Medical School Initiative for RNA Medicine, Harvard Medical School, Boston, Massachusetts, USA.

⁰Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.

Aging Cell +

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September 13, 2024

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View abstract on PubMed

Summary

This summary is machine-generated.

Extracellular vesicles (EVs) from young mice improve liver health and extend lifespan in old mice. A specific microRNA (miRNA), miR-30c, within these EVs shows potential for antiaging liver therapy.

Area Of Science

Gerontology and Regenerative Medicine
Molecular Biology and Genetics
Metabolic and Liver Diseases

Background

Aging is linked to reduced health span, with no approved antiaging drugs.
Extracellular vesicles (EVs) from young donors can prolong lifespan in aged recipients.
The impact of EVs on liver metabolism during aging remains largely unknown.

Purpose Of The Study

To investigate the effects of EVs from young (sedentary and exercised) mice on aged mouse metabolism and liver health.
To identify youth-associated microRNA (miRNA) cargos in EVs that may promote healthy liver function.
To explore the therapeutic potential of miR-30c for age-related liver fibrosis.

Main Methods

Aged mice were treated with EVs from young sedentary (EV-C), young exercised (EV-EX), or aged (EV-A) mice.
Metabolic parameters including insulin sensitivity, locomotor activity, and respiratory exchange ratio were assessed.
Liver fibrosis and stellate cell activation were analyzed, with a focus on miR-30c delivery via engineered EVs.

Main Results

Treatment with young-derived EVs (EV-C and EV-EX) improved insulin sensitivity, increased locomotor activity, and lowered respiratory exchange ratio in aged mice compared to EV-A.
Young-derived EVs reduced aging-induced liver fibrosis.
EVs containing miR-30c mimic reduced hepatic stellate cell activation and fibrosis by targeting Foxo3.

Conclusions

Juvenile EVs can ameliorate age-related metabolic dysfunction and liver fibrosis in mice.
miR-30c, delivered via EVs, is a promising candidate for antiaging liver therapy.
EV-based therapies hold potential for promoting healthy aging and treating age-related diseases.

Keywords:

aging exercise extracellular vesicles fibrosis miR‐30 microRNAs

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