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Metformin accelerates senescence in aged populations

metformin rapamycin

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#1 TaiChiKid

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Posted 07 December 2019 - 06:10 AM

A just released study on the effects of metformin on aged populations:

Late life metformin treatment limits cell survival and shortens lifespan by triggering an aging-associated failure of energy metabolism


A free full link to the study:  https://www.biorxiv....1/863357v1.full



Stabilization of cellular ATP levels alleviates late life metformin toxicity in vitro and in vivo.

    Late life metformin treatment limits cell survival and shortens lifespan.

    Metformin exacerbates aging-associated mitochondrial dysfunction causing fatal ATP exhaustion.

    Old cells fail to upregulate glycolysis as a compensatory response to metformin.

    The dietary restriction (DR) mimetic response to metformin is abrogated in old animals.

    PKA and not AMPK pathway instigates the early life DR response to metformin.



    Degradation of fatal ATP exhaustion may be counteracted by simultaneous use of rapamycin.





#2 8bitmore

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Posted 12 December 2019 - 05:18 PM

This meta study is bunk in my opinion - it conflates findings done on nematodes and mice with studies done on humans. One of the only human linked studies (1) is one showing Metformin's limiting impact on exercise-benefits in older individuals (which is well known) but says nothing about acceleration of senescence at all. Also, said human study is brought up in this sentence:


"In fact, observations consistent with a reversal of metformin benefits at old age and a negative impact of late life metformin exposure on adaptive, motor and cognitive abilities (Konopka et al., 2019; Thangthaeng et al., 2017) have recently emerged from descriptive studies performed in mice and humans."


Which is just rich BS - the mouse study they duly link to prove this point shows (2) that "Overall, metformin supplementation in male mice failed to affect blood glucose, body weights and redox homeostasis at any age." - meaning it has got nothing to do with age - these particular mice failed to respond to metformin at ANY age.


So, it turns out that mice never did well on Metformin due to renal toxicity whereas humana actually benefit on the kidney side of things (3)!


Now just like with any other substance, Metformin can be overdosed and it is entirely possible to get ill from it so my advice would be to dose properly (i.e. not a lot if not diabetic) and get bloodwork done ever so often to check liver/kidneys!



(1) https://onlinelibrar...1111/acel.12880

(2) https://www.ncbi.nlm...les/PMC5287385/

(3) https://www.ncbi.nlm...les/PMC6337137/

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