Metformin is the most commonly prescribed type 2 diabetes drug, yet scientists still do not fully know how it works to control blood sugar levels.
In a new study, researchers found that the diabetes drug could trigger a surprising number of biochemical “switches” for various cellular processes.
This could explain why metformin has been shown to extend healthspan and life span.
The research was conducted by a team from the Salk Institute, The Scripps Research Institute, and Weill Cornell Medical College.
Previously, the only biochemical pathway that was known to be activated by metformin was the AMPK pathway. But the scientists believed more pathways than AMPK might be involved.
In the study, the scientists developed a novel screening platform to examine kinases, the proteins that transfer phosphate groups, which are critical on/off switches in cells and can be rapidly flipped by metformin.
Using this technology, they were able to decode hundreds of regulatory “switch-flipping” events that could affect healthy aging.
The results revealed that metformin turns on unexpected kinases and pathways, many independent of AMPK.
These kinases are poorly understood, but are known to have some relation to cellular stress, which could connect them to the health-span- and lifespan-extending effects observed in other studies.
In fact, metformin is currently being tested in multiple large-scale clinical trials as a health-span- and life-span-extending drug, but the mechanism for how metformin could affect health and aging has not been clear.
The current study indicates that kinases Protein Kinase D and MAPKAPK2 maybe two players in providing these health benefits.
The results broaden the understanding of how metformin induces mild stress that triggers sensors to restore metabolic balance, explaining some of the benefits previously reported such as extended healthy aging.
The big questions now are whether metformin can benefit the health of all individuals, not just type 2 diabetics.
The study is published in Cell Reports.
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