As indicated by some of the comments to a recent post about resveratrol - and why I'm not hot on research to slow aging in comparison to research aimed at repairing aging - I'm failing to clearly make what I consider to be the most important point. I made another go at it as a sequence of ideas in the most recent Longevity Meme Newsletter:
3) Practicing calorie restriction is free, but research is not. The present purposing of the aging research community to metabolic manipulation is expensive, but money isn't the real concern. An opportunity is being lost: the real cost is the slowdown in developing a research infrastructure that is instead purposed towards identification and repair of aging damage, a more efficient way forward to extended healthy lives. This is the difference between tuning your engine and taking it to a mechanic: tuning gets you so far and so far only; at some point, you're going to have to repair the components.
4) It does you no good in the long term to buy an extra decade of healthy life if that's all you get; it was only useful if researchers spent that decade working hard on repairing aging, rather than further metabolic science. There's only so much you can do with slowing aging through metabolic manipulation - the elderly wouldn't benefit, for example - but a working repair mechanism for the cellular damage associated with aging could be used to restore the aged and hold off aging over and over again. It's more efficient and effective.
5) There is more than enough money in the world to have your cake and eat it - to fund both lines of research, metabolic tinkering and repair of damage. But this is not happening now. Successful fields have gravity - they attract new researchers and shape the course of science on a timescale measured in decades; without a great deal of work, the fight against aging will be metabolic manipulation and little else for the foreseeable future. That would leave us rather stranded twenty years from now.
Which earned me some rather sarky comments in private email from one of those fellows who sells resveratrol. So, let's try again, by means of example this time; I'll pick out two early stage technologies that are starting to show promise for a game of compare and contrast. Both involve the age-related damage wrought by free radicals that occurs in - and is caused by - mitochondria, vital cellular components that convert food into more convenient forms of energy to power your cells. You might first want to take a look at a post from last month that summarizes the latest view of the mitochondrial free radical theory of aging, and explains how the accumulation of damage to mitochondria is a root form of aging damage.
First up is the enhancement of the anti-oxidant catalase:
"Rabinovitch's group genetically engineered mice to produce a natural antioxidant enzyme called catalase. The mice lived 20 percent longer than normal mice - on average they lived five and a half months longer than the control animals, whose average life span was about two years
We had differing hypotheses about where putting catalase might do the best in terms of the advantage to life and health of the mice," Rabinovitch explains. So they targeted the gene in three different places in the mouse cells - the cytoplasm, the nucleus - where they thought it might protect the all-important DNA of the cell - and the powerhouses of the cells, the mitochondria - where cells "burn" glucose for energy and churn out high levels of these oxidizing free-radicals. The mice that lived longest had the gene in their mitochondria.
"What we learned was that increasing the levels of catalase specifically in mitochondria was the way in which we could most effectively increase the 'healthspan,' as we call it, the increased time of healthy life for the mice," Rabinovitch says. Mice with high catalase levels in the other cell structures showed only modest life extension.
The catalase soaks up some portion of free radicals before they can attack your vulnerable mitochondrial DNA. Damage to this DNA, as explained in that post I referenced above, leads to an unfortunate chain of events that causes entire cells to rabidly produce damaging free radicals and export them throughout the body. But stop a fraction of the original mitochondrial free radicals from attacking their birthplace, and you have slowed the rate at which one cause of aging happens - you have slowed down aging, and extended healthy life.
Great, right? Well, yes, considered in isolation - and if you are young. If you are old and already damaged, you're pretty much out of luck. Gene therapy to boost your levels of catalase isn't going to do much for you, no matter how many hundreds of millions of dollars were spent getting it from the laboratory and into clinics. It can't repair what has already happened. It's also not so great if you were young at the outset, and after twenty years of research focus and construction of a multibillion dollar industry and scientific infrastructure, there has been little progression beyond ever more sophisticated manipulation of metabolism in this sort of way - you're still aging, and you will still suffer and die as a result.
Let's look at the second technology: protofection. This is a methodology demonstrated to be a means by which scientists will be able to completely replace the mitochondrial DNA in your cells:
Today our team confirmed our previous preliminary data showing that we can achieve robust mitochondrial transfection and protein expression in mitochondria of live rats, after an injection of genetically engineered mitochondrial DNA complexed with our protofection transfection agent. A significant fraction of cells in the brain is transfected with this single injection even though we so far did not optimize the dose.
This achievement has important implications for medicine: protofection technology works in vivo, and should be capable of replacing damaged mitochondrial genomes.
Replacing damaged mitochondrial DNA means completely shutting down the consequences of free radical damage. You're not slowing this aspect of aging, you're stopping it - and for the already aged, you would be reversing this form of aging damage. With a mature protofection technology, people could repair mitochondria every time it was needed - and consider that most folk make it through their first 30 years just fine at the present rate of damage.
It should be quite clear that protofection is a far superior and more efficient answer to free radical damage of mitochondria than any form of antioxidant therapy. Now consider this: in the present day of highly regulated medicine and expensive development, both these technologies would likely cost much the same in money and time to move from where they are now to widespread, safe use in humans. Where would you invest the time and money?
That, then, is the point - the practical difference between slowing aging and reversing (or repairing) aging. Presently, that portion of the scientific community invested in longevity and aging research is heavily - almost completely - weighted towards slowing aging and manipulating metabolism, such as in the case of the catalase work above. If work in repairing aging had as much interest, backing and support, then we could have our cake and eat it - use techniques that slow aging as stepping stones to live in good health to take advantage of techniques that reverse aging. But that is not the case today, and without a great deal of hard work (by organizations like the Methuselah Foundation, amongst others) it will not be the case tomorrow either.
The bottom line is this: we can miss the boat or not - it's up to us.