Study reveals how diabetes drug promotes healthy aging
Metformin may hold surprising benefits in the fight against age-related illness.
ISLAMABAD (ONLINE) - Doctors commonly prescribe metformin to help people with type 2 diabetes lower their blood sugar levels. The drug increases insulin sensitivity through its effects on glucose metabolism.
Metformin may hold surprising benefits in the fight against age-related illness.
However, although there is clear evidence of metformin’s effectiveness, scientists do not fully understand how it interacts with cells and tissues at the molecular level.
Using cell cultures and mice, the researchers identified numerous biochemical switches for turning various cell and molecular processes on and off.
The findings shed light not only on metformin’s mechanism of glucose control, but also on a surprising number of other reactions and pathways.
Large-scale clinical trials of metformin are already under way to test the drug’s effectiveness in extending life span and health span — that is, the proportion of a person’s life span that they spend in good health. However, the underlying biochemistry has been unclear.
Teams from three research centers worked on the study: the Salk Institute for Biological Studies, the Scripps Research Institute — both in La Jolla, CA — and Weill Cornell Medical College in New York.
"These results," says Reuben J. Shaw, one of the study’s corresponding authors, "provide us with new avenues to explore in order to understand how metformin works as a diabetes drug, along with its health-span-extending effects."
"These are pathways that neither we, nor anyone else, would have imagined," he adds.
Shaw is a professor of molecular and cell biology at the Salk Institute and director of the Salk Cancer Center.
More recently, scientists have found that metformin may be effective in a number of other conditions, including obesity, cancer, metabolic syndrome, polycystic ovary syndrome, and nonalcoholic fatty liver disease.
Other recent research has also suggested that metformin may have anti-aging effectsTrusted Source and an ability to protect bone, especially during the early phases of rheumatoid arthritis.
Until the new study, scientists’ understanding of the biochemical effects of metformin was limited to knowing that the drug activates a signaling pathway called AMPK. This pathway plays a key role in balancing energy levels in cells.
Prof. Shaw had also discovered that when nutrients levels are low, the AMPK pathway holds back cell growth and alters metabolism. Researchers have seen this effect in cancer. Knowing this led Prof. Shaw and colleagues to wonder if metformin might also work through other pathways.
New pathways may explain anti-aging effects
For the new study, the teams used a "quantitative proteomics platform" to screen kinases. These are signaling proteins that can switch cell processes on and off.
The researchers found hundreds of kinases whose switching activity responds rapidly to metformin with potential impact on healthy aging. Many of the signaling pathways work independently of AMPK.
Scientists were already aware of two of the pathways — protein kinase D and MAPKAPK2 — and that they concern cellular stress. This could explain the link with healthy aging and the impacts on extending life span and health span.
