Autophagy is, broadly speaking, the process by which your cells recycle damaged components. Cells are packed full of building blocks dedicated to specific tasks, and few of them are designed to last. The average cell is a little powerhouse of dynamic destruction and construction, tearing down and rebuilding organelles left and right. Like all important cellular processes, autophagy is complex, regulated by a web of genes and proteins. The Wikipedia entry gives a good introduction:

In cell biology, autophagy, or autophagocytosis, is a catabolic process involving the degradation of a cell's own components through the lysosomal machinery. It is a tightly regulated process which plays a normal part in cell growth, development, and homeostasis, where it helps maintain a balance between the synthesis, degradation, and subsequent recycling of cellular products. It is a major mechanism by which a starving cell reallocates nutrients from unnecessary processes to more essential processes.

A variety of autophagic processes exist, all sharing in common the degradation of intracellular components via the lysosome. The most well known mechanism of autophagy involves the formation of a membrane around a targeted region of the cell, separating the contents from the rest of the cytoplasm. The resultant vesicle then fuses with a lysosome and subsequently degrades the contents.

But we can say that more autophagy appears to be a good thing. You don't want damaged organelles running wild in your cells; one only has to look at the mitochondrial free radical theory of aging to see where that can lead - a trick of biochemistry prevents mitochondria from being recycled, and ever more damaged cells spew toxins into your body, causing the degenerations of aging that follow.

Scientists believe that a number of the benefits of calorie restriction result from an increased level of autophagy, producing a lower level of damage in your cells at any given point in time. Over at the Immortality Institute forums, you'll find an educational reprint on the process of autophagy:

Autophagy often gets overlooked as "just housekeeping," says Beth Levine, professor of internal medicine at the University of Texas-Southwestern Medical Center at Dallas. In fact, she says, failures in keeping house likely contribute to diseases such as cancer and neurodegeneration. In addition, autophagy wanes with age for reasons that aren't yet clear, says Levine, and is "mechanistically important" in aging itself.

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Other pathways have certainly been implicated in the lifespan extension induced by calorie restriction. Fasting upregulates expression of sir-2 in yeast and worms, and SIRT-2 in mice, and the resulting proteins may help mobilize glucose for use in the cell. At present, no one has tried to link autophagy to the sir-2 pathway, although Levine admits that she's pondered the notion.

Aging is ill defined and certainly multifactorial. The appeal of autophagy to ameliorate normal aging is its capacity as a jack-of-all-trades repair mechanism in the cell. "I believe that the induction of autophagy in caloric restriction-or loss-of-function mutation in insulin signaling-leads to increased degradation of damaged mitochondria and reduction of oxidative stress," says Levine. "And that's probably a downstream pathway that's in common to all these life extension phenotypes."

What interesting times we live in! A great new territory of knowledge and possibility is opening up around new biotechnologies, and aging is becoming open to intervention and ultimate defeat.

Technorati tags: aging, autophagy, biotechnology, life extension, medical research

Posted by Reason at May 3, 2007 8:53 PM | TrackBack (1)