Fight Aging!

You might think of autophagy as a form of self-maintenance for your cells: it is the destruction of damaged and older cellular components such that newly built components can take their place. It is an attractive, intuitive idea that an increased level of autophagy leads to consistantly better function in cells, which in turn leads to longer-lived animals. Over the past years, researchers have demonstrated strong links between autophagy and healthy longevity:

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.

Some of the most interesting work has been published this year and last. If you want a primer on why autophagy is important, and why it is that some damaged cellular components take a heavy toll of life and health, then look back in the Fight Aging! archives :

• On Autophagy
• Autophagy Required For Calorie Restriction Benefits?
• The Prospects for Enhancing Autophagy to Combat Age-Related Degeneration
• All Roads Lead to Autophagy?

What should I find today while meandering through PubMed but another longevity mechanism tied to increased autophagy. You might recall that researchers are achieving impressive results in mice by manipulating p53 - even managing to break the link between cancer protection and aging to give both added longevity and added cancer protection, not one at the cost of the other. In the paper I noticed today, we see that manipulating p53 is another way of manipulating autophagy for beneficial results on health and longevity:

The effects of p53 on whole organism longevity are mediated by autophagy:

The tumor suppressor protein p53 has a major impact on organismal aging. Recently it has become clear that p53 not only controls DNA damage responses, senescence and apoptosis but also plays a major role in the control of autophagy. Thus, deletion, depletion, or inhibition of p53 induces autophagy in human, mouse and nematode cells.

We therefore tested the hypothesis that the mutation of the p53 orthologue CEP-1 might increase the life span of Caenorhabditis elegans through an increase in baseline autophagy. For this, we evaluated the survival of nematodes lacking cep-1, alone or in combination with RNA interference with the autophagy gene bec-1 (which encodes the orthologue of Atg6/Beclin 1).

cep-1 mutants exhibited a prolonged life span. While BEC-1 depletion during adult life did not cause significant modification of the life expectancy of wild type controls, it did reduce the increased life span of cep-1 mutants down to approximately normal levels. These results indicate that the life span-extending effect of the cep-1 mutation is mediated by autophagy. These results lend support to the hypothesis that autophagy has a broad positive impact on organismal aging.

Given the level of funding and interest in calorie restriction mimetics, I imagine that the development of autophagy-enhancing drugs will proceed in the much the same way over the next few years.