Good news for Rapamycin users… though this study focuses on metformin:
Age-related tendon disorders are closely linked with tendon stem/progenitor cell (TSPC) senescence. However, the underlying mechanisms of TSPC senescence and promising therapeutic strategies for rejuvenation of TSPC senescence remain unclear. In this study, the senescent state of TSPCs increased with age. It was also verified that the AMPK inhibition/mTOR activation is correlated with the senescent state of TSPCs. Furthermore, a low dose of metformin mitigated TSPC senescence and restored senescence-related functions, including proliferation, colony-forming ability, migration ability and tenogenic differentiation ability at the early stage of aging. The protective effects of metformin on TSPCs were regulated through the AMPK/mTOR axis. An in vivo study showed that metformin treatment postpones tendon aging and enhances AMPK phosphorylation but reduces mTOR phosphorylation in a natural aging rat model. Our study revealed new insight and mechanistic exploration of TSPC senescence and proposed a novel therapeutic treatment for age-related tendon disorders by targeting the AMPK/mTOR axis at the early stage of aging.
I am wondering how important is the dose of metformin for the AMPK inhibition/mTOR activation.
Many years ago I read in Life Extension Magazine about the role of metformin as an anti-ageing medication. At the time it was recommended to take 850 mg 3 times a day. At the present time it seems that people take up to 1000 mg for the purpose. The maximum recommended dose for the treatment of diabetes is 2500 mg/day.
How are you reading this statement in the abstract of the paper?
I’m reading the statement as saying that mTOR activation was correlated with the senescent state of the TSPCs… and therefore the inhibition of mTOR via rapamycin (or metformin as used in this study, though rapamycin is a much more potentent mTOR inhibitor) restored the function of the cell.
@macneu2299 mentions in her statement “the dose of metformin for the AMPK inhibition/mTOR activation”, but I “think” the paper is saying the metformin increased AMPK and inhibited MTOR…
The article mentions that “Furthermore, a low dose of metformin mitigated TSPC senescence and restored senescence-related functions, including proliferation, colony-forming ability, migration ability and tenogenic differentiation ability at the early stage of aging”. My question is about a questionable anti-ageing dose of metformin. As I mentioned, Life Extension Magazine cited studies recommending 850 mg three times a day for years. I know that the TAME study will be using only 500 or 1000 mg per day.
Do we actually know an effective dose for anti-ageing, or only for the treatment of diabetes.
We don’t know the effective dose for anti-aging, but Nir Barzelai and the designers of the TAME trial are betting that 1500mg SR / day is the right dose:
Presentation on the TAME trial where they talk about dosing: