LONGECITY

Aspirin Recapitulates Features of Caloric Restriction

The latest from Guido Kroemer's lab.  First author Pietrocola.

The age-associated deterioration in cellular and organismal functions associates with dysregulation of nutrient-sensing pathways and disabled autophagy. The reactivation of autophagic flux may prevent or ameliorate age-related metabolic dysfunctions. Non-toxic compounds endowed with the capacity to reduce the overall levels of protein acetylation and to induce autophagy have been categorized as caloric restriction mimetics (CRMs). Here, we show that aspirin or its active metabolite salicylate induce autophagy by virtue of their capacity to inhibit the acetyltransferase activity of EP300. While salicylate readily stimulates autophagic flux in control cells, it fails to further increase autophagy levels in EP300-deficient cells, as well as in cells in which endogenous EP300 has been replaced by salicylate-resistant EP300 mutants. Accordingly, the pro-autophagic activity of aspirin and salicylate on the nematode Caenorhabditis elegans is lost when the expression of the EP300 ortholog cpb-1 is reduced. Altogether, these findings identify aspirin as an evolutionary conserved CRM.

 

 

 

This article should verify a lot of the comments and referenced work here.

 

 

While salicylate readily stimulates autophagic flux in control cells, it fails to further increase autophagy levels in EP300-deficient cells, as well as in cells in which endogenous EP300 has been replaced by salicylate-resistant EP300 mutants.

That part doesn't sound good.

Aspirin is a double edged sword though with its broad spectrum cox inhibition. 

You can get the Willow bark which lacks the acetylated part but I never tried that. I do take about 2grams of Aspirin once every ten days or so. Tried taking 100mg every day but that gave me some kind of stomach problem, probably an ulcer. Which cleared up within weeks of discontinuation of daily aspirin.

 

 

 

While salicylate readily stimulates autophagic flux in control cells, it fails to further increase autophagy levels in EP300-deficient cells, as well as in cells in which endogenous EP300 has been replaced by salicylate-resistant EP300 mutants.

 

That part doesn't sound good.

 

Aspirin is a double edged sword though with its broad spectrum cox inhibition. 

 

I don't think that means anything bad.  It just means that salicylate doesn't improve on existing levels of autophagy and that EP300 acetyltransferase activity inhibition is the mechanism of action.  If it's already low/inhibited, then autophagy is already taking place and aspirin doesn't improve it further.

https://youtu.be/Gm626MgpveI?t=50m32s

Kroemer Interview.  Beginning at Fasting/Autophagy part.

Lower protein acetylation three ways:

1. Inhibit Acetyl-CoA formation (citrate lyase)
2. Inhibit acetyltransferase (ep300)
3. Activation of deacetylases, sirtuins (resveratrol)

Salicylate appears to act via the second method.