Friday, November 6, 2015

Anti-aging drug will put you on a very nasty waiting list.

A commentary article in the 18 September issue of Science describes an 'anti-aging' drug that an investigator wants to use in clinical trials.  We guess that scientists will never stop pushing the envelope, and perhaps the very job of science is to do that.  But at least, when it's costly and has consequences, the consequences should be acknowledged up front so that anyone supporting the idea knows what their getting into.

Of course the usual cast of characters, experts convened by NIH to hear the proposal, did their usual hyperbole job (one quoted as saying that "this is a ground breaking, perhaps paradigm-shifting trial.").  Experts are, after all, not wholly disinterested when it comes to research funding.

The proposed idea is to follow a few thousand older people for at least five years to see what happens to them on a chosen long-known-safe drug related to diabetes treatment.  They say, but without any real evidence that I could discern from the article, that they're not trying to extend life particularly, but just to add healthy years to one's lot.  Because these lucky survivors will purportedly be healthier, their medical needs will be less so the burden on the health-care system will be less, too. Yes, fund this work and reduce health care costs!  Does that sound like snake oil?

In this effort the idea is just to choose a known test drug to show proof of principle with the idea that the 'real' anti-aging compound will some day be discovered.  Despite the hype and breathless promotion by aging researchers (who are also researching aging!), from an actual biological point of view this is likely to be yet another stroll through Dreamland, and we've had plenty of those in regard to Fountain of Youth ideas.  Anyone remember monkey glands?  Or 'orthomolecular medicine'? Vitamin C?  Indeed, vitamin D?

The reason we make our skeptical assertion is that forestalling age-related diseases mainly means slowing down the process of degeneration.  That essentially is the expected effect of the proposed study.  But in reality, if this were successful it would mean, first, people having more years at risk for more decrepitude or for diseases to arise.  And secondly, it means the newly experienced years will almost inevitably involve living with more morbidity, that is, less quality of life, for longer times.

Why is this? In a nutshell, some cause or system failure will eventually get each of us.  Only cryopreservers can seriously think otherwise (and they're deluded).  Most of the causes of late adult death involve gradual decay of some biological system(s).  Often one thing leads to another: bones broken in a fall lead to infection or immobility that leads to something else, or livers and intestines may be fine but neural processes decline, and so on.  Stopping one decay will directly enable other decays to take its place in the survivor who would have passed away from the first one.  Our lifespan seems mainly to be based on surviving all roughly independent, or correlated, causes until one finally gets you.  The alternative is that lifespan is calibrated by some single factor, and many candidates have been advanced, like loss of chromosomal telomere length.  Nonetheless, the former, multiple-cause view is clearly applicable to a great extent.

The reason is that the processes of neural decay, mutational cause of cancer, clogging or bursting of arteries, toxic buildup in tissues, physical wear on joints, slowing down of cell division in the gut, lung, and immune systems and so on are undoubtedly at least partially local and independent, and simply not due to any single underlying cause.  This means that even if there is a magic calibrator with some major delaying or slowing effect, as does seem likely, given the different lifespans of various mammal species, that slowing down many or all decays will just extend the period in which the person will have to suffer through many different, simultaneous, forms of falling apart.

This is not a pretty picture, but based on history it is the nearly inevitable result of life-extension. Preventing pneumonia is, so to speak, a great way to increase cancer and dementia risks.  So will taking lifetime regimens of the newly discovered statin-replacement drugs that have recently been so highly touted.  So would the piling up of billions of elderly people in a resource-crowded world.

Facing up to the reality, in the absence of any solace from religious hopes, is a major challenge in our age of science.  But the real world intrudes nonetheless.  The grim reaper will get us in the end, of course.  And the grim reaper of our wallets will be fleecing us all the way there.

1 comment:

Rick said...

I'm not sure this is right. It seems to count on an assumption that all such declines will occur at a roughly equal pace, and that most of us are killed by gradual declines over years. Perhaps this is true, and perhaps there is no way to slow or prevent gradual decline, but it doesn't seem to be obvious that there is no way to sharpen the gradient a bit while keeping lifespan the same. I would assume that the decline of (say) a single fatal case of pneumonia is rather more rapid than the decline of Alzheimer's (and far less miserable). Untreated diabetes is a more gradual and miserable decline than a catastrophic MI late in life.

This piece seems to imply that we all have a roughly equal period of misery and decline at the end of our lives, and that the only way to get more good years is to stack on more bad years later on. I just don't see much reason to believe that. It seems obviously false in many ways: an elderly person who works hard to maintain her muscle mass might very well have died from the same stroke at 80 whether or not she went to the gym twice/week, but it seems pretty obvious that her doing so would contribute more to her quality of life than being sedentary.