Metformin & Rapamycin Show Combined Benefits in New Study
Channel: Lifespan News
Date: 2022-08-28

Rapamycin and metformin are viewed by many as the two most promising anti-aging drugs, but now scientists have found that these drugs can work hand in hand and show combined benefits, boosting each other's effectiveness and blocking side effects - or at least that’s what we’ve seen in mice.

When tested by the Intervention Testing Program metformin failed to significantly increase lifespan in mice. However, in combination with rapamycin, it worked synergistically, leading to a drastic increase in median and maximal lifespan.

In this new study, the researchers put the “combination hypothesis” to the test again, using male mice of a common pre-diabetes model. The mice received either rapamycin, metformin, or a combination from 12 to 30 weeks of age.

Being pre-diabetic, these mice usually gain a lot of weight with age. Metformin treatment did not alleviate this trend, but both the rapamycin and combination treatments allowed the mice to maintain normal weight until the end of the experiment.

The mice used in this experiment are of a variety known to develop fatty liver. While metformin alone had only a modest effect, fatty liver was completely prevented by rapamycin, both alone and in combination with metformin.

While generally considered safe, metformin is suspected to be toxic to the kidneys. In this new study, metformin treatment substantially elevated kidney inflammation levels and the albumin/creatinine ratio, a measurement of kidney damage. Rapamycin did exactly the opposite, and the combined treatment was just as good as rapamycin alone in preserving kidney function.

The researchers gathered their results in a table that illustrates the effects of the combination treatment. In every case in which one or both drugs had a beneficial effect, this effect was fully preserved. In one case, metformin enhanced rapamycin-induced insulin sensitivity despite having no effect on its own. In three cases, rapamycin-induced deleterious effects were alleviated or blocked by metformin, and in two cases rapamycin's benefits were maintained in the combination treatment despite metformin independently working in the opposite direction.

Despite this study’s limitations, such as using only diabetes-prone male mice, this new study demonstrates an intriguing synergy between the two molecules. Combination treatments may ultimately be the way to go.

SOURCES AND FURTHER READING
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LSN: Metformin’s link to birth defects - https://youtu.be/sUHDpMRmeC4
LSN: Metformin’s link to reduced exercise gains - https://youtu.be/WQE34DUcbsk

Lifespan.io article - https://www.lifespan.io/news/rapamycin-and-metformin-show-synergy-in-mice/ 

Rapamycin/metformin co-treatment normalizes insulin sensitivity and reduces complications of metabolic syndrome in type 2 diabetic mice - https://onlinelibrary.wiley.com/doi/full/10.1111/acel.13666

Evidence for Rapamycin Toxicity in Pancreatic β-Cells and a Review of the Underlying Molecular Mechanisms - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3717855/

Longer lifespan in male mice treated with a weakly estrogenic agonist, an antioxidant, an α-glucosidase inhibitor or a Nrf2-inducer - https://pubmed.ncbi.nlm.nih.gov/27312235/

The effects of addition of coenzyme Q10 to metformin on sirolimus-induced diabetes mellitus - https://pubmed.ncbi.nlm.nih.gov/29228766/

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