Fight Aging!

The Interventions Testing Program has been underway at the National Institute on Aging for something like a decade now. The aim is to rigorously test all the supplements and drug-like compounds thought to modestly extend life in mice on the basis of older studies, and the results to date have largely been a demonstration that very few such items do in fact extend life in mice. Sufficient rigor was lacking in many old exploratory studies, some of which were conducted in advance of the present widespread understanding that any inadvertent reduction in calorie intake in studied mice is going to extend life. Introducing novel compounds into the diet or which might cause nausea turns out to be an excellent way to make that happen.

So it goes. A lot of these past results were simply wrong, just as a majority of results in the sciences are wrong. Research is hard and has a high failure rate, which is why we need the scientific method in order to sift the gold from the dross. It has taken until now for there to be enough of an interest in treating aging, as well as a critical mass of researchers willing to stand up and say it is possible and plausible to treat aging, for more expensive assessment programs like this to emerge. The ITP is by no means the only such effort to obtain greater rigor in data on ways to extend life in mice. I should also point out this initiative:

Historic BAIT Project Underway at the Buck Institute

With BAIT, [researchers] are building a resource for tracking how mice age, both in response to drug treatment and under normal physiological conditions. It's a "big data" project that is yielding terabytes of information on physiological markers of health including cardiac function, metabolism, bone density, body composition, activity and blood pressure, among others. "We are creating the gold standard for looking at variability in aging in mice."

"For a long time, we as an aging research community really have been focused on the survival curve. The goal had been to find treatments or genetic mutations that increase lifespan in mice, pushing the survival curve to the right. However, there have been precious few examples of understanding what the functional consequences of pushing the survival curve are. It's not necessarily a given that if you increase lifespan you will increase healthspan. Data from BAIT will provide us with numerous jumping-off points to push the research forward. We want to move therapies into the clinic; knowing how treatments impact specific functional parameters in the mice could give us a way to guide clinical trials in humans. This is the vital information that's been lacking."

The initial BAIT project involves 770 genetically identical mice that entered the study at 20 months of age (roughly equivalent to a 60-year-old human). One subset is aging normally; other subsets are being individually treated with four drugs that have already been shown to increase lifespan in simple animals such as worms and flies. BAIT is already the largest study in the world looking at functional aging in mice, and now that the pipeline is established, there is no reason not to scale up even further. [Researchers] think that, given the resources, BAIT could handle up to 50 or 60 compounds, providing a next-generation resource for drug development.

This is exciting stuff for those who feel that there is promise in working on ways to marginally slow aging through drug development, such as varied initiatives focused on calorie restriction mimetics. But a more sober assessment of what is possible and plausible suggests that this will gather a great deal of new knowledge but fail to produce ways to greatly extend life. The goals for the metabolic manipulation approach to slow aging, such as those put forward by the Longevity Dividend advocates, are to add five to ten years to healthy life by the mid-2030s. The cost of a serious attempt to achieve this goal will be stupendous: the entire research and pharmaceutical industry focused on turning a fraction of the present drug development pipeline to these efforts. We already know how much this costs and the sort of results (or lack of same) to expect, as we can just look at the past decade of sirtuin research to see in the vicinity of a billion dollars spent and very little to show for it yet.

The end result of drug development to slow aging is a treatment that is of limited use to old people even if it works, and most of us will be old by the time any such thing arrives. Aging is a process of damage accumulation, and slowing aging merely means a slower pace of that damage accumulation. Not much good if you are already so damaged that your mortality risk is high and quality of life low. The only way to make radical breakthroughs in the decades ahead, to produce methods of rejuvenation that can add decades of renewed, improved health for people already old, is to focus on - and fund - something other than the drugs and dietary compounds that so many people fixate on. Regular readers know by now that "something other" is best represented by the SENS research program, but any group working on ways to repair and reverse the underlying damage that causes aging rather than just slow it down has potentially far more promise than the mainstream approach of drugs to slow aging.

We don't have all the time in the world. If funding institutions and researchers continue to focus on scientific programs that are both inordinately expensive and very unlikely to produce therapies with meaningful effects for people who are already old, then we will miss our chance at a radical extension of healthy life far beyond present limits.