Fight Aging!

I wanted to point out an example of research into the biochemistry of calorie restriction as an example of how scientists progress in their investigations of cellular biology. If the cell is a machine, then the biotechnology revolution has provided scientist-mechanics with wrenches to pull out cogs and screwdrivers to force the settings on inner switches. It has also bequeathed reams of disordered notes from a thousand other mechanics, and from all this sense and understanding has to eventually emerge.

So how do you find out what does what in a cell, and by extension in the entire organism that the cell belongs to? Pulling out pieces to see what they were needed for isn't such a bad strategy, especially guided by educated guesswork and related discoveries made by many other engineers. Good educated guesswork is very possible these days, and the cost of chasing down a dead end (in time and money) is falling all the time - it makes sense to explore and take risks. In this vein, a recent paper shows how scientists added more genes to the list of those needed for longevity produced via calorie restriction in worms, though the story is better told in the science press:

Carrano's next set of experiments focused on WWP-1's potential role in the regulation of lifespan. When she genetically engineered worms to overexpress WWP-1, well-fed worms lived on average 20 percent longer. Deleting PHA-4, which was discovered in Dillin's lab and so far is the only gene known to be essential for lifespan extension in response to diet restriction, abolished the life-extending effects of additional WWP-1 placing the ubiquitin ligase as a central rung on the same genetic ladder as PHA-4. Without WWP-1, cutting down on calories no longer staved off death.

When a study by others found that UBC-18 interacts with WWP-1, Carrano wondered whether it could play a role in diet-restriction-induced longevity as well. She first confirmed that the UBC-18 functions as an ubiquitin-conjugating enzyme and gives WWP-1 a hand. She then tested whether it played a role in lifespan regulation. "Overexpression of UBC-18 was not enough to extend the lifespan of worms but depleting it negated the effects of caloric restriction," says Carrano, who is busy looking for potential substrates of the UBC-18-WWP-1 ubiquitination complex.

Cogs, switches, and dials - and keep careful note of the results of each manipulation. That's the way it works behind the curtain. The processes of biochemistry common between most species are an enormous jigsaw puzzle, worked on by thousands of scientists and technicians. At the end of the road, there will be one or more ways to increase human life span by some amount through improving the metabolism of the next generation.

People who live all their life with a better, human-engineered metabolism will reap the benefits, but I doubt these future methods will be of much benefit to people already old when development is complete. That will include most of us, I would imagine, given the likely timescales involved in research and development. Changing metabolism is fundamentally a way to slow aging, not reverse it. If you're already old, you're out of luck. This is one of the reasons I support work into repairing the damage of aging over work to manipulate metabolism so as to slow aging.

By all means practice calorie restriction - it's free, available now, and the science backs the claim that it does great things for your long term health - but don't believe that deciphering the mechanisms of calorie restriction is the grand future of engineered longevity. It isn't. A true reversal of aging, and far greater healthy longevity are all plausible through other lines of research, however: don't work to merely slow the damage of aging, rather work to reverse and repair the known forms of damage.

Carrano, A., Liu, Z., Dillin, A., & Hunter, T. (2009). A conserved ubiquitination pathway determines longevity in response to diet restriction Nature DOI: 10.1038/nature08130