There are many failures on the path from early study in cells to successful medical technology applied to humans. A success in cell cultures often turns out to be infeasible in animals, as cells in culture are not a part of a larger tissue and organism and thus not subject to the same signals, stresses, and influences. Work in organoids, tiny sections of living tissue, can certainly help to bridge this gap, but even an organoid that accurately reflects the structure and function of an organ is still not subject to the real ebb and flow of a living animal, all of the interactions with other tissues and systems.

Success in animal studies, usually carried out in mice, can fail in larger mammals for any number of reasons. While there are many similarities between mammals, there are just as many differences. The popular science article below focuses on the biochemical differences between species as a reason for the leap between mice and humans to fail so often. I think it overemphasizes the point, and fails to offer viable suggestions for an alternative. In the field of aging, I'd have to say that there are two important factors for a high failure rate, only one of which is really an issue of species differences, and both can be traced back to a poor high level strategy for the development of means to treat aging and age-related disease.

The first is that short-lived species exhibit vastly greater slowing of aging and life extension when stress response mechanisms are upregulated. So calorie restriction, increased autophagy, heat stress, and other hormetic effects produce sizable gains in life span, up to 40% or more in mice. Where direct comparisons can be made, we know that these methods produce no such result in humans. While beneficial for health, the existence of effect sizes of larger than five years of additional life is very implausible given the existing data. Yet members of the aging research community continue to put the majority of their effort into developing therapies that boost these stress responses. Results fail to translate because effect sizes in humans are much smaller and much less reliable, and clinical trials are looking for sizable, reliable outcomes.

The second issue is that most of the work on age-related conditions starts with the end stage disease state and works backward. Researchers end up trying to develop therapies based on manipulating proximate causes that are very late in the development of pathology, far removed from root causes. This tinkering with the operation of the disease state is far more vulnerable to small differences in cellular biochemistry between species, and tends to produce marginal results at the best of times. Small benefits based on tinkering with a complex, disarrayed biochemistry have a way of vanishing or becoming highly unreliable firstly in the move between species, and secondly in clinical trials once larger numbers of people and their individuals differences become involved. Again, this is a problem that exists because of the way in which research and development is conducted: it is the result of a poor choice of strategy.

The right approach to aging is to target and repair the known root causes. Many of these are the same in their important aspects in all mammals, such as the accumulation of senescent cells, or the class is the same and only the importance of different members of the class varies, such as accumulation of cross-links or lipofuscin, in which the specific molecules to target are different in mice and humans. Further, the effect sizes resulting from successfully reversing root causes of aging and age-related disease should be larger and more reliable in any species: it covers many downstream consequences, and even if those consequences are different in different species, they will still be reduced. This gives a greater expectation of success in future human clinical trials based on the existence of mouse data only.

Don't believe the mice