Asprosin-driven metabolic-epigenetic rewiring attenuates mesenchymal stem cell senescence with therapeutic benefits for infarcted hearts.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Senescent mesenchymal stem cells (MSCs) exhibit impaired self-renewal, limiting their therapeutic potential. While multi-omics have revealed downregulation of pan-tissue Fbn1 with aging, particularly in MSCs, the role of its derivative asprosin in MSC senescence is unknown. To elucidate the regulation of senescence/reparative function in aged MSCs by asprosin and evaluate its therapeutic potential for aged MSC-mediated cardiac repair after myocardial infarction (MI). Serum asprosin levels were measured by enzyme-linked immunosorbent assay, and asprosin expression in MSCs was determined by western blotting. Fbn1 expressiondynamics with aging were assessed using public transcriptomic/single-cell datasets. Gain/loss-of-function (lentiviral overexpression/CRISPR-Cas9 knockout) studies were employed to validate the role of asprosin. The effects of recombinant asprosin on senescent MSC proliferation, migration, and pro-angiogenic secretion were tested. Glycolytic flux (Seahorse), metabolites (glucose uptake, G-6-P, lactate), and lactylation (pan-lysine, H3K18la) were measured. Integrated H3K18la CUT&Tag/RNA-seq was performed to identify downstreamtargets, and therapeutic efficacy was assessed in an MI mouse model using intramyocardial injection of asprosin-overexpressing aged MSCs. Circulating asprosin was correlated with adipose mass in young obese mice but was attenuated in aged ob

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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