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              Advocacy & Research for Unlimited Lifespans


Mitochondrial Permeability Uncouples Elevated Autophagy and Lifespan Extension.

mtorc2 sgk autophagy aging longevity mitochondrial permeability

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#1 Engadin

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Posted 03 April 2019 - 06:56 PM


  • SGK1 regulates autophagy in both C. elegans and mammalian cells
  • Elevated autophagy and mPTP opening shorten lifespan in sgk-1/mTORC2 mutant worms
  • SGK-1 phosphorylates mPTP component VDAC1 on Ser104, promoting its degradation
  • Loss of SGK function exaggerates mPTP-dependent hepatic ischemia/reperfusion injury


Autophagy is required in diverse paradigms of lifespan extension, leading to the prevailing notion that autophagy is beneficial for longevity. However, why autophagy is harmful in certain contexts remains unexplained. Here, we show that mitochondrial permeability defines the impact of autophagy on aging. Elevated autophagy unexpectedly shortens lifespan inC. elegans lacking serum/glucocorticoid regulated kinase-1 ( sgk-1) because of increased mitochondrial permeability. Insgk-1 mutants, reducing levels of autophagy or mitochondrial permeability transition pore (mPTP) opening restores normal lifespan. Remarkably, low mitochondrial permeability is required across all paradigms examined of autophagy-dependent lifespan extension. Genetically induced mPTP opening blocks autophagy-dependent lifespan extension resulting from caloric restriction or loss of germline stem cells. Mitochondrial permeability similarly transforms autophagy into a destructive force in mammals, as liver-specific Sgk knockout mice demonstrate marked enhancement of hepatocyte autophagy, mPTP opening, and death with ischemia/reperfusion injury. Targeting mitochondrial permeability may maximize benefits of autophagy in aging.
This is it. The rest is not accessible so far but IMHO it's interesting enough to post it here. We will post the whole study once reason or me put our hands on it. Take it for granted.


Edited by Engadin, 03 April 2019 - 07:02 PM.

#2 Rays

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Posted 04 April 2019 - 10:27 AM

So, blocking the pores would help autophagy and increase lifespan, do I understand that right? E.g. using C60oo?



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#3 Harkijn

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Posted 18 April 2019 - 03:36 PM

So, blocking the pores would help autophagy and increase lifespan, do I understand that right? E.g. using C60oo?

I wish I understood more about this, too.

I hope some knowledgeable people chime in once they have digested the full study. Here it is.

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Also tagged with one or more of these keywords: mtorc2, sgk, autophagy, aging, longevity, mitochondrial permeability

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