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All Roads Lead to Autophagy?

Some research groups are making the case that all roads lead to autophagy, the process of tearing down and replacing worn cellular components, when it comes to enhancing healthy longevity through adjustments to metabolism. Examples include calorie restriction (CR) - which you can manage all by yourself today - or drugs that mimic some of the effects of CR on regulatory mechanisms in our biochemistry, which you're going to have to wait a little longer for. But it's all down to increased autophagy, they say:

The better known life extension mechanisms in lesser animals are all driven by changes in autophagy - or so say the autophagy specialists. It's true that the various hyperspecialized communities of modern biology are overly cloistered and ignorant of one another's research, but the autophagy researchers are assembling compelling evidence for this position: "Here we show that mutational inactivation of autophagy genes, which are involved in the degradation of aberrant, damaged cytoplasmic constituents accumulating in all aging cells, accelerates the rate at which the tissues age in the nematode Caenorhabditis elegans. According to our results Drosophila flies deficient in autophagy are also short-lived. We further demonstrate that reduced activity of autophagy genes suppresses life span extension in mutant nematodes with inherent dietary restriction, aberrant insulin/IGF-1 or TOR signaling, and lowered mitochondrial respiration. These findings suggest that the autophagy gene cascade functions downstream of and is inhibited by different longevity pathways in C. elegans, therefore, their effects converge on autophagy genes to slow down aging and lengthen life span. Thus, autophagy may act as a central regulatory mechanism of animal aging.

Which is interesting, because other research groups are fairly sure that the enhanced longevity provided by these sorts of metabolic adjustment is accomplished through lowered levels of chronic inflammation and free radical generation:

This review focuses on the emerging evidence that attenuation of the production of reactive oxygen species and inhibition of inflammatory pathways play a central role in the antiaging cardiovascular effects of caloric restriction.

The evidence on both sides is compelling, but it can't be both all autophagy and all inflammation and free radical reduction, and it can't be just one or the other. Conflicting evidence and theories with good experimental backing on all sides are usually a good sign that there is something important left to be discovered, some shift in the overall picture of the field. For example, a comprehensively described link between autophagy, inflammatory processes and free radical generation. For now we're still missing a unifying view of the many known metabolic and genetic changes that increase longevity in mammals - how do they work?

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