Metformin, a commonly used drug for type 2 diabetes, has been found to not only lower blood sugar levels but also extend lifespan, according to a new study led by researchers at Massachusetts General Hospital. The study, published in eLife, discovered that metformin promotes longevity by stimulating the production of ether lipids, which are crucial for cell membranes.
The researchers conducted experiments using the roundworm Caenorhabditis elegans, which shares a significant portion of its proteins with humans and has an average lifespan of about two weeks. By silencing individual genes in these worms and exposing them to metformin and its sister drug phenformin, the scientists identified the genes required for the drugs to extend lifespan. They found that genes responsible for increasing the production of ether lipids are essential for the longevity-promoting effects of the drugs.
Further investigation revealed that increasing ether lipid synthesis alone, by overexpressing a key ether lipid biosynthetic enzyme, was sufficient to extend the lifespan of the worms. This process triggered a metabolic stress defense response through a factor called SKN-1, similar to the mammalian protein Nrf, resulting in a longer lifespan.
The researchers believe that promoting the synthesis of ether lipids could be a promising strategy for promoting healthy aging and reducing the impact of aging-related diseases in humans. However, they emphasize the need for additional studies in mammalian models and clinical trials to determine the effectiveness and safety of targeting ether lipid synthesis.
Senior author Alexander A. Soukas, MD, PhD, Associate Director of the MGH Center for Genomic Medicine, expressed the potential implications of the study, stating that promoting ether lipid biosynthesis could be a novel therapeutic target for healthy aging and aging-related diseases. He suggests that dietary or pharmacologic interventions to enhance ether lipid synthesis may one day represent a strategy for treating these conditions.
Overall, this research sheds light on the role of metformin in promoting longevity and highlights the potential benefits of increasing ether lipid production. The findings open up new avenues for exploring interventions that could support healthy aging and potentially extend human lifespan. However, more studies are needed in order to fully understand the viability and effectiveness of targeting ether lipid synthesis in humans.
