What Can Other Primates Teach Us About Aging and Neurodegeneration?

It has been said that the only thing worse than using animals in medical research is to refrain from the use of animals in medical research. It is both terrible and necessary. Throughout the modern history of medical science animal studies have been needed in order to make progress, not just in human medicine, but also veterinary medicine. Many people are opposed to animal studies, and to the degree that this is motivated by compassion - and leads to sensible forms of advocacy - this is to their credit. Unfortunately all too few of these individuals follow the logic though to its end and thus devote near all of their efforts to oppose the animal farming, hunting, and fishing industries. These activities cause harms to animals that tower over those of research. All the animal studies carried out in a year are a rounding error against a few hours of the meat industry.

That aside, animal studies will one day soon be a thing of the past. Some will be replaced by the use of engineered tissue sections, but eventually all will give way to experiments that run on simulation platforms, coupled with a much more modest use of engineered tissues to validate those simulations. Even the early steps on this road will be more effective and far cheaper than maintaining animal colonies and lineages for use in research. The only reason that this transition hasn't yet occurred is that only now has tissue engineering arrived at the point of mass production of functional tissue sections that mimic the real thing closely enough to be useful. I would hope that the farming of animals one day goes the same way, and that we as a species continue on a somewhat upward slope of culture and enlightenment that leaves this and other presently acceptable forms of institutional violence behind us. That is no doubt a much longer and harder road than merely transforming life science research.

Primate studies are already in decline. They are far more expensive than studies in shorter-lived species and far more difficult to arrange in the present climate. Any new study similar to the decades-long calorie restriction studies in rhesus macaques now coming to their final years is unlikely to take place given today's culture and pace of technological progress. Thus I think that these researchers are arguing for the last days of a paradigm that is firmly in its sunset period:

Lessons from the analysis of nonhuman primates for understanding human aging and neurodegenerative diseases

Why do we need animal models? The simplest answer to this question is to increase our general knowledge, to experimentally test theories. Animal model usefulness is manifold, from the study of physiological processes to the identification of disease-causing mechanisms. They are necessary tools for solving the most serious challenges facing medical research. In aging and neurodegenerative disease studies, rodents occupy a place of choice. However, the most challenging questions about longevity, the complexity and functioning of brain networks or social intelligence can almost only be investigated in nonhuman primates (NHPs). Beside the fact that their brain structure is much closer to that of humans, they develop highly complex cognitive strategies and they are visually-oriented like humans. For these reasons, they deserve consideration, although their management and care are more complicated and the related costs much higher.

NHPs have significantly contributed to understanding of aging and neurodegenerative diseases. Aging NHPs show striking similarities with elderly humans. Most of our understanding on the biological changes observed during aging comes from studies in rodents because they present clear advantages (short life span, fully characterized genetic aspects, easy genetic manipulation...). However, rodents and humans diverged much earlier than humans and NHPs, and this is likely to have led to fundamental differences in their aging processes. In one pioneering work, for example, researchers compared the transcriptome of the cerebral cortex in aging mice, rhesus macaques and humans, providing a broad view of the evolution of aging mammalian brain. They found that only a small subset of age-related gene expression changes are conserved from mouse to human brain, whereas such changes are highly conserved in rhesus macaques and humans.

Due to their genetic proximity to humans and their highly developed social skills, NHPs are extremely valuable as experimental animal models. However, as the number of available animals is restricted for ethical reasons and also because of the high cost and large space required for breeding colonies, NHPs should only be used when no other suitable method is available to fill the gap of our knowledge. In any case, rodent (or other small animal models) and primate experimental models need to be used in parallel in order to obtain robust and complementary information. Alongside other models, nonhuman primates should have a unique place in the overall aging and neurodegenerative research strategy.


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