Some people believe that metformin is a cornerstone to an anti-aging protocol.
Here’s research indicating that it has been found to cause problems with mitochondrial function. Multiple studies have demonstrated that metformin impairs mitochondrial function, primarily by inhibiting complex I of the mitochondrial respiratory chain. Here are the key findings from the research:
## Inhibition of Mitochondrial Respiration
Metformin has been shown to decrease mitochondrial respiration in a dose-dependent manner:
– It reduces oxygen consumption rates in cells, particularly affecting the rate of respiration used for ATP synthesis[3].
– The drug causes a decrease in basal, maximal, ATP-linked, and uncoupled oxygen consumption rates in intestinal cells[1].
– Studies in skeletal muscle of both healthy and diabetic rats showed that metformin impaired in vivo and ex vivo muscle oxidative capacity[2].
## Specific Effects on Mitochondrial Complex I
Metformin’s primary target appears to be complex I of the mitochondrial respiratory chain:
– It selectively inhibits complex I, leading to decreased NADH oxidation and reduced proton gradient across the inner mitochondrial membrane[5].
– This inhibition is weak and reversible but has been confirmed in various species and biological models, including cancer cells[5].
– The drug limits respiration and citric acid cycle activity in isolated mitochondria, indicating that the mitochondrion is the primary target for these effects[3].
## Alterations in Mitochondrial Morphology and Gene Expression
Research has also revealed that metformin affects mitochondrial structure and genetics:
– Treatment with metformin alters mitochondrial network morphology, with a higher percentage of cells showing punctate mitochondria compared to controls[1].
– The drug affects the expression of mitochondrial genes[1].
## Impact on Energy Efficiency
Metformin treatment leads to changes in cellular energy metabolism:
– Cells treated with metformin become energetically inefficient, displaying increased aerobic glycolysis and reduced glucose metabolism through the citric acid cycle[3].
– The drug causes an increase in the fraction of mitochondrial respiration devoted to uncoupling reactions, further reducing energy efficiency[3].
## Time and Dose-Dependent Effects
The mitochondrial dysfunction caused by metformin appears to be both time and dose-dependent:
– Higher doses of metformin result in more pronounced effects on mitochondrial function[2][4].
– Prolonged exposure to metformin increases the damaging effect on mitochondria in human platelets[4].
## Implications for Different Cell Types
The effects of metformin on mitochondrial function can vary between cell types:
– Cancer cells exposed to metformin show a greater compensatory increase in aerobic glycolysis compared to non-transformed cells[3].
– Studies have demonstrated mitochondrial dysfunction in various cell types, including intestinal cells, skeletal muscle cells, and human blood cells[1][2][4].
In conclusion, the research strongly supports that metformin causes mitochondrial dysfunction, primarily through its inhibition of complex I of the respiratory chain. This effect is observed across various cell types and experimental models, and it appears to be both dose and time-dependent.
Citations:
[1] https://www.nature.com/articles/s41598-021-81349-7
[2] https://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0100525
[3] https://pmc.ncbi.nlm.nih.gov/articles/PMC4147388/
[4] https://www.lunduniversity.lu.se/lup/publication/4254193
[5] https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2019.00294/full