Considering the whole of the past thirty years, it is fairly safe to say that studies showing improved longevity in animal models have a terrible track record when it comes to the reproduction of findings. Small gains in life expectancy in one study promptly evaporate when it is attempted by other groups. Very few approaches to slowing aging can be reliably reproduced, and the most well-studied of those, calorie restriction, is probably the cause of many of the early failures. It used to be the case that all too few researchers controlled for the effects of calorie restriction: it is easy to make animals eat more or less as a consequence of pharmaceutical interventions, and the results due to changed calorie intake are larger than the results due to most of the interventions tested. The Interventions Testing Program has spent much of the last fifteen years demonstrating that most prior mouse studies of interventions thought to modestly slow aging should be taken with a grain of salt. The same is also true of studies in lower animals, in species with much shorter life spans, but where length of life is affected to a greater proportional degree by environmental influences.

The authors of the open access paper below try to put some numbers to the difficulties involved in picking out small changes in the aging process due to an experimental intervention. The animals involved tend to have quite variable life spans, and are very prone to life expectancy changes based on the details of their environment. This state of affairs requires larger numbers of animals and better statistical approaches to have any confidence in sifting out useful data. But the wrong conclusions are drawn, I think. The point of view of these researchers is that the way forward is to keep on chasing small effects on aging, and to improve the state of experimental design in order to make it more practical to find those small effects.

This is a ridiculous position. What should in fact happen is for the research community to put aside the lines of work that produce only small and erratic effects, stop digging into the biochemistry of exercise and calorie restriction as a gateway to mediocre therapies, and focus instead on biotechnologies with results that are reliable, reproducible, and large enough to be clearly identified even given the challenges. Today that means senolytics capable of clearing senescent cells, cell therapies, amyloid clearance, other line items resulting from the SENS approach of damage repair, and little beyond that short list. If the last few decades has taught us anything, it should be that attempts to tinker with the operation of metabolism in order to slightly slow aging by recapturing some of the effects of calorie restriction are expensive, unreliable, and produce only small gains. Why then is this metabolic tinkering with poor outcomes still the primary choice for most of the research community? It makes little sense, at least to those of us interested in the development of working, effective therapies that can produce rejuvenation in old humans.

Computational Analysis of Lifespan Experiment Reproducibility