A three-drug mix clears aging cells at lower doses
The accumulation of senescent cells in tissues is one of the recognised drivers of aging. A new three-drug combination appears to clear those cells even at lower doses than previously used. But the results are preliminary.
When cells stop dividing but refuse to die, they become senescent. They accumulate in tissues and secrete substances that damage surrounding cells and fuel inflammation. Drugs that selectively remove senescent cells are called senolytics. Until now, the most widely used combinations have been based on dasatinib and quercetin.
The researchers combined navitoclax (also known as ABT-263), dichloroacetate, and metformin into a combination they call DMA. Navitoclax has long been known as a senolytic, but at higher doses it damages platelets. By combining it with the other two compounds, the researchers were able to reduce the navitoclax dose tenfold. In cell culture experiments and in mice, DMA selectively eliminated senescent and malignant cells without harming healthy ones.
Results in mice
In aged mice, acute administration of DMA improved physical performance. Prolonged administration extended lifespan. These are relevant findings, but the study was published in the journal Aging and the experiments have not yet been replicated by independent research groups.
Far from clinical application
The combination has not been tested in humans. Metformin and dichloroacetate each carry their own side effect profiles, and the long-term effects of DMA as a combination are unknown. There are also many competing senolytics in development. Whether DMA stands out will only become clear through comparative research. The findings are an interesting signal, but do not yet support therapeutic claims.
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