Heath and Aging

Biology of Aging

Is what's good for mice good for men?

A lot of research findings seem to tell us what is good—or bad—for yeast, mice, roundworms (C. elegans), or fruit flies (Drosophila melanogaster). 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, rats, and nonhuman primates, have many biological mechanisms and genes that are similar to humans. They also experience many of the same physiological changes (changes in the body) 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 (like modifying a gene to measure its effects on health or longevity) 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. The animals typically have a very structured daily regimen with limited exposure to pollutants, stressors, or other elements that could otherwise affect lifespan and health span.

Animal models

Here are some animals commonly studied in aging research.

Roundworm (C. elegans)
Fruit fly (drosophilia melanogaster)
Mouse (mus musculous)
Rhesus monkey (macaca mulatta)

Different types 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. The roundworm’s 2- to 3-week lifespan makes it another ideal model for identifying and studying genes that might affect longevity. In a landmark study, NIA-funded researchers found that reducing the activity of a set of genes, called daf, increased roundworm lifespan by three- or even fourfold. Daf genes are involved in the roundworm’s ability to enter a type of hibernation stage, called diapause, to survive periods of food scarcity. This research would not have been as feasible if conducted using an animal model with an average lifespan of 10 or 20 years.

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 to NIA 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.

A Different Approach: Comparative Biology

mouse
naked mole rat
Courtesy of Thomas Park, Ph.D.,
Univ. of Illinois at Chicago
MOUSE
Lifespan: 4 years

NAKED MOLE RAT
Lifespan: 17 to 28 years

One approach to aging biology research is called “comparative biology.” It involves comparing two or more similar species that have very different lifespans—one lives much longer than the other—to understand how the longer-lived species has, as one NIA-funded researcher puts it, “exceptional resistance to basic aging processes.” Comparative biology studies generally focus on species that live at least twice as long as their close relatives.

A few possible theories explain what may be taking place among these longer-lived animals:

  • They experience a slower rate of age-related decline.
  • They can survive even when their organs and/or systems break down and have minimal function.
  • They are better able to tolerate cellular damage or diseases.

The naked mole rat, a mouse-size rodent that lives underground, has been widely used in comparative research. It lives approximately 17 years in the wild and more than 28 years in captivity. Its relative, the mouse, lives a maximum of 4 years. What accounts for this startling difference? Naked mole rats have lower metabolic rates and body temperature, meaning that they require less energy to survive. They have low concentrations of blood glucose (blood sugar), insulin, and thyroid hormone, so they are less susceptible to certain diseases. Naked mole rats are better able to withstand some types of biological stress and, at this point, there has never been a case of cancer reported in these animals. All these factors and likely others yet to be determined contribute to their healthier and longer life.

 

Publication Date: November 2011
Page Last Updated: January 18, 2012