A Tangible Benefit of Artificially Boosting Autophagy

The latest issue of Rejuvenation Research (Volume 12 Number 2) is available online. Leading the papers is an examination of what an artificial increase in autophagy levels does for mammal biochemistry. Autophagy, and macroautophagy in particular, is the process by which a cell recycles damaged components. In theory more recycling means less long-term damage caused by malfunctioning systems in a cell, and a general improvement in the operation of your tissues as the number of broken cell components are reduced:

Aging is characterized by several metabolic changes responsible for the decline of certain functions and the appearance of age-related diseases, including hypercholesterolemia, which is the main risk factor for atherosclerosis and cardiovascular disease.

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Caloric restriction (CR) was shown to increase longevity and prevent age-related diseases in various organisms, and to counteract the age-associated increase in plasma cholesterol. CR was thought to operate through the stimulation of the process of macroautophagy. The aim of this work was to investigate the effect of the stimulation of macroautophagy on age-associated cholesterolemia.

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Results show that the stimulation of macroautophagy reduces the total LDL and high-density lipoprotein (HDL) cholesterol plasma level to juvenile values, and triglycerides levels even lower.

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.

Anti-aging effects of anti-lipolytic drugs:

Genetic disruption of insulin and insulin-like signaling pathways may extend lifespan. Hyperinsulinemia and insulin resistance may accelerate aging.

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It is concluded that life-long weekly-repeated transient inhibition of insulin secretion by antilipolytic drugs may have an anti-aging effect, additive to the anti-aging effect of a milder caloric restriction. Speculation is that transiently lower plasma insulin levels might stimulate the anti-aging cell-repair mechanism autophagy, which has longer lasting effects on cell housekeeping.

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