Fight Aging!

Here I'll point out a view of the great divide in aging research from the other side. I have long argued that the most important divide in the field of aging research is between (a) the minority position of those who see aging as an evolved program, so that, for example, epigenetic changes occur that cause altered cellular behavior that in turn leads to an accumulation of damage, dysfunction, and death, and (b) the majority position of those who see aging as a matter of accumulated damage occurring as a side-effect of the normal operation of metabolism, and that damage results in epigenetic changes, dysfunction, and death. There is a horse and a cart, and some argument over which is which.

Researchers in fact know a great deal about the differences between old tissue and young tissue. They have a very good catalog of those differences. They also have a pretty good catalog of the dysfunctions in specific organs and tissues that accompany age-related disease. The middle ground between those two things, the enormously complex biochemical interactions spanning decades of time that produce aging, is much more of a blank spot on the map. Only tiny slices have been mapped, and it is this gap that allows the freedom to theorize over whether change produces damage or damage produces change.

Why is this important? Because whether you stand on one side or the other of this theoretical divide determines which approach to treating aging you should favor. Treatments for aging must aim at root causes to be effective. If change, such as epigenetic change leading to altered levels of proteins in cells, is the root cause of the damage of aging, then treatments should consist of restoring the right protein levels and epigenetic markers rather than addressing damage. But if damage is the root cause of aging then treatments should be repairing that damage. The potential rejuvenation therapies that are on the wrong side of the line will likely be ineffective in comparison to those on the right side of the line.

Obviously, given my support for the SENS approach to treating aging, I'm in the damage camp. I think that the evidence, such as the presence in old tissues of harmful cross-links that our biochemistry cannot break down, strongly supports the view that aging is caused by damage accumulation, and the observed epigenetic and protein level changes are reactions to that damage. Here, however, is a view from the other side, the programmed aging camp:

Aging is an accumulation of damage. If we want to return the body to a more youthful state, we're going to have to repair that damage. Or ... the body never forgets how to be young. Given the appropriate signaling environment, the body will restore itself to a youthful state. The future of medicine is the future of anti-aging medicine. I don't think anyone seriously disputes this. Infectious diseases are a minuscule problem compared to a century ago, and with hygiene, good public health practices, and responsible restraint in applying antibiotics, we may hope to avoid a return to the days when tuberculosis and syphilis were pandemic. We are fast learning to treat congenital disorders, and safe gene therapies are already being tested.

This leaves diseases of old age as the next frontier. To slow the progress of aging, there is no doubt that signaling approaches work in animals, and will work (probably with less efficacy) in humans. Caloric restriction (CR), exercise and other forms of hormesis are the best approaches we know at present. Pills (e.g. metformin) may offer some of the benefits of CR without the hunger, and an "exercise pill" has been proposed. The next step is to actually reverse aging, to restore the body to a more youthful state. Among those of us who advocate research in the technology of age reversal, there are two prevailing paradigms. I am with the school that says the same signaling approach can be extended to trick the body into thinking it is younger than it is, and the body will renew its cells and replace damaged biomolecules on cue. The other school says that once the toothpaste is out of the tube, it's not going back in. We will have to engineer prosthetics, use bioengineering and regenerative medicine to replace body parts that have worn out.

In the beginning, anti-aging medicine was thought to be fanciful, if not impossible. How could human engineering improve on processes that Nature has been perfecting for a billion years? Then a science of regenerative medicine began very slowly chipping away at that conventional wisdom, and a glimmer of hope pointed to promise of fixing the body directly with engineering, at least in the long run. But a funny thing happened along the way. There are indications in many areas that the body knows perfectly well how to rejuvenate itself, and we need only learn to speak the body's (biochemical) language in order to say, "Have at it!" A few people like me are pointing out that this contradicts everything we thought we knew about evolutionary biology, and that the "selfish gene" is in need of an overhaul. But bench scientists are choosing to sidestep this theoretical debate and simply to do the practical thing. They are pursuing a signaling approach because it works.

I would argue that the signaling approach is largely characterized by failure to obtain meaningful outcomes, and at great cost. Just look at the end result of sirtuin research; enough money expended to fully implement SENS rejuvenation programs in mice, and nothing to show for it but greater knowledge of a small slice of our biochemistry. Where there are successes in more recent years, these seem to result from activation of stem cells in old tissues - and restoring stem cell populations is on the SENS agenda - without any accompanying repair of other root cause damage. This will produce benefits, and fortunately it seems that putting damaged cells in damaged tissues back to work has far less of an effect on cancer risk than was feared, but this doesn't do anything to clear out issues such as amyloids, lipofuscin, and persistent cross-links.

Link: http://joshmitteldorf.scienceblog.com/2015/11/19/anti-aging-medicine-two-paths-diverge/