Sonntag, 19. März 2017

To be fair, I am getting ahead of myself - Is the Longevity Dividend real?

Often I like to say that Täuber's paradox (ref. 1) proves that aging research is more cost-efficient than other disease centered research. The idea is that the longevity dividend (ref. 2) strictly follows from this concept. To be fair, we don't know for certain. First of all, maybe we should rephrase it more precisely. It seems highly plausible that aging research is cost-efficient given - let's call it - the Täuber asymmetry. Slowing aging by about 1% is probably as effective as cutting cancer rates by 50%.

There are three key assumptions that must be satisfied in addition to Täuber's:
1a. Aging can be slowed as a whole, or at least many age-related diseases driven by the same underlying cause can be slowed together
1b. This is not an idiosyncratic one time deal like calorie restriction
2. The feasibility of (1a). The task must be technically achievable and cost-efficient

1a. Is close to certain. Calorie restriction (CR) is the proof of principle and despite a lot of controversy it is shaping up reasonably (ref. 3). This assumption could have been wrong if aging were driven by millions of changes and millions of genetic interactions that follow no underlying logic. The truth is definitely in-between. While aging is indeed multifactorial, it can be decelerated by the regulation of a few signaling pathways. Each pathway itself might result in thousands of important changes, but this has no bearing on the end result.

1b. If we want to use the longevity dividend for our benefit, we have to ask what comes next? Once we have CR-mimetics, for example, is there any way to do better? Perhaps CR is the only conserved anti-aging pathway and it will be impossible to easily extend lifespan beyond a certain limit? Maybe CR only affects healthspan and that's all that is reasonably achievable? (ref. 3)

Robust and additive lifespan extension by CR-related and especially unrelated interventions would strengthen assumption (1a) and especially (1b).

2. Here, the test case is probably rapamycin. CR is considered "impossible" to implement on a global scale and no true CR-mimetic has emerged until recently. Rapamycin inhibits a nutrient sensing pathway that is also suppressed by CR (mTOR signaling) and is much closer to clinical application. Let's keep in mind that current, under-funded aging research does not need to prove that (1a, 1b, 2) is completely true by finding a perfect drug. Given the funding situation, it would border on a miracle if we quickly found a drug that has fewer side-effects than rapamycin yet still slows aging by 10%. That would be like curing cancer, just considerably better and on <1% of the cancer research budget!

References

1. Keyfitz, N. (1977). What difference would it make if cancer were eradicated? An examination of the Taeuber paradox. Demography, 14(4), 411-418.

2. Olansky, S. J., Perry, D., Miller, R. A., & Butler, R. N. (2007). Pursuing the longevity dividend: scientific goals for an aging world. Ann NY Acad Sci, 1114, 11-13.

3. Mattison, J. A., Colman, R. J., Beasley, T. M., Allison, D. B., Kemnitz, J. W., Roth, G. S., ... & Anderson, R. M. (2017). Caloric restriction improves health and survival of rhesus monkeys. Nature Communications, 8.