A fair amount of chatter is taking place over recent research into the protein p16INK4a and the gene producing it. The name indicates it is an INhibitor of cyclin-dependent Kinase 4A; romantic, slipstreamed naming schemes are the first casualty of complexity in science - and it doesn't get much more complex than biochemistry. I noted the EurekAlert! release at the Longevity Meme, but the HHMI News article is an easier read and more to the point as to what folk are thinking could be done with the research. See what you think:
A single molecular switch plays a central role in inducing stem cells in the brain, pancreas, and blood to lose function as they age, researchers have found. Mice lacking that switch show considerably reduced aging-related decline in stem cell function and tissue regeneration.
People tend to think that old tissues have less regenerative capacity because they are wearing out. This work shows that they are not just wearing out; they are actively shutting themselves down.
While the finding could ultimately lead to drugs to slow or reverse degeneration in the brain and other tissues, the researchers cautioned such treatments would have to be balanced against the chance of increasing cancer risk in patients.
I think if you asked before these studies whether you could delete a single gene and rescue stem cell function in multiple tissues, and neurogenesis in an old brain, many people would have said that aging is such a complex phenomenon that you would not get a significant effect.
This last quote aptly illustrates why there is great interest in this research - it's always exciting to find a common trigger for many different aspects of aging biochemistry.
Much of the discussion presently taking place relates to evolutionary explanations for this mechanism: the well known trade-off between aging and cancer that are seen in many cellular mechanisms:
Morrison theorized that p16INK4a is a suppressor of stem cell function that evolved as part of the regulatory machinery that also includes proto-oncogenes that encourage cell proliferation. "We are all evolutionarily selected to, on the one hand, maintain regenerative capacity of our tissues through adult life so that we can repair our cells and survive injuries - while on the other hand, limit proliferation in our tissues with age, so cells don't divide out of control, causing cancers," he said. "And the way that we achieve that balance is by having proto-oncogenes that promote proliferation come into balance with tumor suppressor genes that inhibit proliferation. This work shows one way that this balance changes with age.
While these tumor suppressor mechanisms don't even exist during fetal development, where cells must divide rapidly, it makes sense that they become stronger in old age, when we are more at risk of getting a cancer. So, the benefit is that genes like p16 allow us to get older before we get cancer, but the bad news is that they make us lose function with age.
Beyond the whys and wherefores, the temptation is, as always, to latch onto the latest idea and what-if your way forward. What if this all works much the same way in humans? What if reliable cancer therapies pan out by 2015? Wouldn't that make therapies directed at p16 worth exploring as a path towards healthy life extension?
From where I sit on the sidelines, it seems that tinkering with the structure of the engine - building better components for hot-swapping on the go - is not as utilitarian a path forward as developing the means to repair accumulated age-related damage to the present engine. Improving components is a matter of slowing aging; repairing damage is a matter of preventing and reversing aging.
Look at it this way: you might gain as much in the first decade of full-on commercialization from the results of either of these two different philosophies of development, but replacing a component of your biochemistry in order to slow aging is a one-time deal per component. You change your biochemistry, and there you go, running on the same old timer with a few extra ticks of the second hand. With a working repair technology, you can keep coming back again and again until something else becomes the limiting factor to your health and life span.
That said, there's no such thing as useless knowledge in biochemistry; it's all grist for the mill of the next few decades. We'll be hearing more about p16INK4a, I'm sure, as research into aging, cancer and stem cells continues to overlap and reinforce mutual progress.