Of mice, men and aging!

By Arvind M. Dhople, Ph.D., Professor Emeritus, Florida Tech

A lot of research findings seem to tell us what is good – or bad for yeast, mice, roundworms, or fruit flies.  Does that mean it will work for you?  Animal models are essential to research in the biology of aging.  Fruit flies and roundworms, along with more complex organisms like mice, rates, and nonhuman primates have many biological mechanisms and genes that are similar to humans.  They also experience many of the same physiological changes with aging. 

                Therefore, these animals can be used as models of human aging and human physiology, despite the obvious differences in appearance.  Scientists can use some exploratory approaches in animal models such as worms, flies, and mice that would not be possible in humans.  They also can better isolate the variable they want to investigate because animal studies are conducted in tightly controlled environments.

                Different type of studies use different animal models.  Animal models with a short lifespan take less time and fewer resources to study from birth to death and to test interventions that might affect the aging process.  Scientists might favor a fruit fly when studying a possible genetic target for an intervention to increase longevity, for example, because their average lifespan is only 30 days.  This allows researchers to measure the effects in about a month. 

                After scientists establish a possible intervention in one animal model, they then apply the intervention to increasingly complex organisms.  They might work their way up from worms or flies to mice and then to larger mammals, such as nonhuman primates.  At each step, researchers carefully study if the intervention has the same effect on the comparable biological pathway.

                Sometimes it does not.  Part of the reason might be that while mice, for example, have only a slightly larger number of genes than worms, and the genes in mice and worms serve similar functions, the activity of mouse genes is different and somewhat more complex than that of worms.  As a result, a genetic intervention that increases a worm’s lifespan by fourfold might have a significantly less impressive effect on a mouse’s lifespan.  For similar reasons, an intervention might be promising in mice, but that does not mean it will work the same way or at all in humans.

                Studies in animal models closer to humans, such as monkeys or other nonhuman primates, can be key to understanding how basic discoveries might apply to humans.  They are essential for pre-clinical studies, an intermediary step between research in animal models like mice and clinical studies in humans.  Studies in nonhuman primates, for example, have demonstrated in recent researchers how normal age related changes in the heart influence risk of heart disease.  They have also been important for testing interventions to lower risks of heart disease, such as drugs to decrease blood vessel stiffness.

                So, if something works to slow aging in mice, worms, fruit flies, or monkeys, does that mean it will definitely work for you?  The answer is no.  Certainly, data from animal studies provide critical insights to the aging process and can form the basis for testing potential interventions.  But direct testing in humans is essential before an intervention can be considered safe and effective.