Hormonal
Metformin treatment increases DICER1 protein levels by promoting the nuclear translocation of the RNA-binding protein AUF1, which stabilizes DICER1 mRNA and leads to the upregulation of specific microRNAs (e.g., miR-34a, miR-125) that inhibit cellular senescence.
Metformin, used for type 2 diabetes, appears to slow cellular aging by stabilizing a protein called DICER1. This stabilization allows the cell to produce specific microRNAs that prevent cells from becoming 'zombie' senescent cells, which drive inflammation and aging. This effect is observed at standard therapeutic doses in humans and equivalent doses in mice, suggesting it may contribute to the drug's potential anti-aging benefits beyond glucose control.
Here, we show that metformin treatment increases the levels of the microRNA-processing protein DICER1 in mice and in humans with diabetes mellitus. Our results indicate that metformin upregulates DICER1 through a post-transcriptional mechanism involving the RNA-binding protein AUF1. Treatment with metformin altered the subcellular localization of AUF1, disrupting its interaction with DICER1 mRNA and rendering DICER1 mRNA stable, allowing DICER1 to accumulate.
Why this rating
Strong evidence from multiple models (mice, human cell lines, human clinical cohort), though direct human longevity data is not yet presented.
Source
Metformin‐mediated increase in DICER1 regulates microRNA expression and cellular senescence
Nicole Noren Hooten et al. · Aging Cell · 2016
DOI 10.1111/acel.12469
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