Fight Aging!

Autophagy is, put simply, the process by which cells recycle damaged components. Of course like all cellular processes the reality on the ground is anything but simple, and autophagy interacts with all sorts of other processes in ways that can produce counter-intuitive results. But the weight of evidence points to more and better autophagy as beneficial overall, most likely because it leads to fewer lingering damaged components inside a cell. Repeated throughout all your cells, this should result in better functioning tissue, fewer errant biological systems, and a longer life - remember that aging itself is nothing more than accumulated damage and the thrashing of systems trying to adapt to that damage.

I've discussed the importance of autophagy numerous times in the past; you might look at one of the summary posts in the archives, for example. In short:

• Studies show extension of life span in laboratory animals by increasing autophagy
• Autophagy is required for calorie restriction to extend life span, and is boosted by the practice of calorie restriction
• Plausibly, more autophagy might extend life span by more rapidly eliminating damaged mitochondria

In any case, I thought I'd point out a good introduction to the scientific study of autophagy. This is an open access review paper on autophagy in C. elegans, one of the most studied of all species. This species of nematode worm has few cells, doesn't live very long, is cheap to breed and examine, and is very well documented. Despite being a tiny worm, many of its metabolic processes are sufficiently similar to those in mammals that researchers can learn from it - one of the most fortunate accidents of evolution is the degree to which central, longevity-influencing mechanisms of metabolism have been conserved across a vast range of species.

The mechanisms by which autophagy mediates lifespan extension are not yet understood. However, one possibility is that the increase in lifespan is mediated through the autophagy-dependent nonspecific or selective removal of damaged mitochondria, decrease in levels of intracellular reactive oxygen species, and subsequent protection against oxidative damage.

Such a mechanism would overlap with the presumed means by which autophagy may protect against genomic instability and tumor progression. It would also provide a framework for the conceptual integration of the oxidative damage theory of aging and the known stimuli that influence aging through autophagy-dependent mechanisms in C. elegans, including dietary restriction and insulin-like signaling.

Many of the long-lived mutants in C. elegans are resistant to oxidative stress and many mutations that decrease mitochondrial electron transport are long-lived, whereas conversely, mutations that increase oxidative damage shorten lifespan in C. elegans. Thus, longevity in C. elegans (and potentially other organisms) may be mediated either by mutations that directly affect cellular generation or breakdown of reactive oxygen species, or indirectly, decrease reactive oxygen specifies via upregulation of the autophagic turnover of the damaged organelles that generate these harmful species.