The leading causes of death worldwide -- heart disease, stroke, cancer, diabetes, and Alzheimer’s — are diseases of aging. Yet there’s much more research into treating these diseases than preventing them.
The young science of biogerontology has discovered evidence that these diseases could likely be prevented by slowing or reversing the process of aging itself.
- Age-related diseases have common cellular causes, the so-called hallmarks of aging.
- Not all animals exhibit these hallmarks; in fact, some whales, sharks, and turtles live for centuries with no evidence of frailty or illness.
- Genetic modifications of animals in the lab have created longer-lived, healthier worms, flies, and mice.
- Over 50 drugs have been reported to extend life in mammals.
So, what's the most efficient way to find out how to extend these successful anti-aging results to humans?
Our plan is to identify the best possible example of a drug that extends life in animals -- a large, reproducible effect, from a safe drug, that isn't just an artifact of laboratory conditions or strain-specific genetics -- so that it'll have the best chance of also working on humans.
Verifying Promising Results
Most studies that show a lifespan-extending effect have never been independently replicated. We’d like to change that.
We’re writing grants to biogerontologists to run lifespan studies on rodents, investigating treatments that have already shown preliminary evidence of effectiveness, and prioritizing those with the largest effect sizes on longevity. In some cases we commission our own studies from contract research organizations.
Our Current Short List of Drugs To Test:
- C3 Carboxyfullerene
These are drugs which have been found to have large effects on animal lifespan, and good supporting evidence of aging-preventative effects, but haven't yet been independently confirmed by a reproducibility project like the Interventions Testing Program.
In other words, these are the drugs for which we believe the "value of information" is highest; the results are important if true, but there's still uncertainty about whether the experiments will replicate, so it's worth finding out.
High-Throughput Automated Phenotypic Screens
To expand our search for life-extending drugs to a broader range of compounds, we need to lower the cost per experiment. This can be done by using a short-lived invertebrate, such as C. elegans, and testing many drugs in parallel to see if they extend lifespan and health, using an automated system (with robotically-controlled cameras and machine learning algorithms for detecting patterns in motor behavior) to test whether animals treated with various drug compounds live longer or age slower.
Automation technology enables us to do experiments cheaply enough that we can run a nearly brute-force search through many possible drugs to see if any are effective anti-aging drugs. So far, invertebrate drug screens for lifespan have been quite successful in finding new anti-aging drugs; it just remains to scale up the process.
Factorial Lifespan Study
Once we've completed Steps 1 and 2, and have some drugs with good mammalian and invertebrate evidence of effectiveness, the next thing to test is whether combinations of those drugs work better than single drugs.
This doesn't have to be prohibitively expensive. A factorial study design, in which each animal receives a random subset of the drugs we test, requires far fewer animals than running separate studies for all the drug combinations.