Arguing for Daphnia as a Model for Discovery in Therapies for Aging

The most commonly used animal models in aging research are nematode worms, flies, and mice. The ubiquitous use of animal models for discovery of mechanisms of aging and assessment of therapies to potentially slow or reverse aging is a matter of economics. It is more cost effective to carry out studies in lower animals with short life spans, even given the sizable fraction of discoveries that turn out to be inapplicable to longer-lived mammals, or even outright misleading. A fair amount of effort goes towards improving the cost-effectiveness of short-lived model organisms in this regard. A number of groups explore the use species that fall outside the usual set, such as daphnia, a class of small aquatic crustaceans.

There is a vast body of literature where people claim that certain drugs, diets, or regimens extend the lives of model organisms such as ants, worms, flies, fish, or mice. People perform an intervention, measure how long the animals live, get an extension of median life of 10, 15, or 20 percent, and publish a paper. There are several problems with this approach. One problem is that papers - even those on the same species - often use different controls, making it impossible to compare results. We're lacking nice, standardized data about life span across laboratories and across organisms.

My colleagues and I realized that we need a standardized, scalable system we can use to test how drugs, diets, and other interventions affect behavior, reaction to stimuli, and additional measures of health span. We started developing a system using Daphnia magna, a species of water flea that has been used in toxicology and environmental research for decades, but hasn't been used to study aging.

What's so great about Daphnia? The species has a life span of one month, and even though it's an invertebrate, it is a complex organism. It is beautifully transparent, with a beating, two-chambered heart, an innate immune system, eyes, a brain, and muscle tissue. In fact, when we use electron microscopy to zoom in on the cells of Daphnia, we see that the neurons and muscle cells look very similar to human neurons and muscle cells. Daphnia is also extremely sensitive to small concentrations of drugs.

Our recent paper is establishing the baseline for Daphnia as a new model organism for studying aging. We describe the system in detail, including how we set up the tank, fed the animals, removed new offspring, and set the light cycles and temperature. These appear to be boring details, but the whole point is getting the boring details right. We are developing a set of routines that are needed to raise Daphnia in a standardized way that is also scalable.



It would be cool if the authors of this paper could sell the tanks to further enable people to do their own experiements. They have a smarttanks site

It would also be good if someone could test a few of the recently proposed senolytics such as dastinib + quercetin, and festin on daphnids.

The full paper:

One limit of this system is that it can only really be used for water soluble small molecule drugs at present.

Posted by: jimofoz at March 10th, 2022 11:36 AM
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