Autophagy vs. cholesterol

Over at Fight Aging!, Reason has penned a very nice piece of analysis on a recent article demonstrating that stimulation of one autophagic pathway can reduce plasma lipoproteins and triglycerides. From the blog post:

A Tangible Benefit of Artificially Boosting Autophagy

The researchers used a compound to block lipolysis in order to provoke greater levels of autophagy in rats. Interestingly, for all that this is a huge change to mechanisms known to be important to all the major metabolic processes, it has a fairly narrow effect in the biochemical area of interest:

[The action of the compound does not require] the counteraction of the age-related increase in lipoperoxidation, and only involves a restoration of the numbers of LDL receptors on liver membranes to juvenile levels.

Which is unfortunate, given that peroxidation of lipoproteins like LDL is one way in which damaged mitochondria spread increasing destruction through the body’s tissues. You’d think that more macroautophagy would mean fewer damaged mitochondria, and therefore fewer oxidatively damaged lipids, but apparently not. Or not within the timescale of this study, anyway.

An aside on the liver and it’s levels of receptors: last year researchers demonstrated a way in which liver function could be restored through boosting the number of receptors to keep them at youthful levels. That and this research are two quite different topics, but this is an interesting commonality. I wonder where else receptor levels might crop up in relation to aging and important metabolic processes involving the liver’s specialized tasks?

Given the present interest in developing calorie restriction mimetic drugs, I expect increasing amouts of money and interest to flow into tinkering with autophagy in the years ahead. All the same reasons and hoped-for outcomes apply. If you’re interested in the history of antilipolytic compounds in longevity research, you should do some digging at PubMed – see for example, this paper from the same folk back in 2003. They’ve been working on this for a while.

As Reason points out, this is reminiscent of last year’s report that stimulating another flavor of autophagy (chaperone-mediated autophagy, in contrast to the macroautophagy studied in this paper) can delay hepatic aging.

Questions arising:

  • Do the treated rats live longer? As the saying goes, only time will tell. Presumably the lifespan curves are already underway; unfortunately, rats live a pretty long time so it might be a while before we know the answer.
  • What is the target cell, if any? Is the decrease in blood lipids a consequence of every cell in the body upregulating autophagy and therefore needing more cholesterol and triglycerides in order to rebuild membrane-bound organelles, or is this a consequence of the drug acting mainly on specific tissues/organs? Especially if this pathway is to be targeted by drugs or, in the long term, genetic engineering, it will be important to find out where the action is taking place.
  • On a related note: Is there a down side? I’m wondering whether the effects of accelerating macroautophagy will be uniformly beneficial to all cell types. I’m especially concerned with respect to cognitive function: In worm and fly, age-related neuronal death is mediated by autophagy and there’s building evidence that the same is true in mammals. (This makes sense: Cellular homeostasis is a balance between creation of new components and destruction of old ones; one can easily imagine a delicate and finicky cell like a neuron losing control of this balance if the rate of degradation were to suddenly rise.)

ResearchBlogging.orgStraniero, S., Cavallini, G., Donati, A., Pallottini, V., Martini, C., Trentalance, A., & Bergamini, E. (2009). Stimulation of Autophagy by Antilipolytic Drugs May Rescue Rodents from Age-Associated Hypercholesterolemia Rejuvenation Research, 12 (2), 77-84 DOI: 10.1089/rej.2008.0806



  1. Yes, there is a downside. Bacterial pathogens that exploit or subvert autophagy may increase in population.

    If you would write about that article I linked to: “Autophagy in intracellular bacterial infection”

    I have the article but I am a lowly computer technician instead of a highly qualified molecular biologist but I will try to learn as much as I can.

Comments are closed.