MDI Biological Laboratory
Aging

Comparative Biology: Animal Models Strut Their Stuff

  • March 14, 2022
Scientists at the MDI Biological Laboratory use the comparative model approach to understand the basic biology of tissue regeneration and aging. Thanks to evolution and common ancestry, we humans actually share a large portion of our DNA with fish, worms, and salamanders. Humans and zebrafish, for example, share 70% of the same genes; 84% of human genes known to be associated with human disease have a zebrafish equivalent. That’s a lot of similarity. 

 

At MDIBL, researchers are particularly focused on the mechanisms of aging and regeneration. Non-mammalian model organisms like C. elegans, zebrafish, African turquoise killifish, and the axolotl regenerate naturally in ways that humans cannot. By decoding the instruction manual for their regenerative abilities, we can develop new strategies to enhance our natural ability to repair and regenerate damages tissues and slow or reverse the degenerative changes that occur as we age.

Zebrafish

We maintain a colony of 20,000 zebrafish, which are native to the Himalayan region and the Ganges River in India. Zebrafish are a great model for research because they are easy to breed, hatch in 2.5 days, and live for about two years.

Four faculty at MDIBL use the zebrafish:

  1. Jim Coffman studies how long-term exposure to stress affects how stress responses develop in baby zebrafish. Chronic stress, traumatic experiences, and toxic environmental exposures early in life can have persistent developmental effects, as well as trans-generational effects.
  2. Iain Drummond established the zebrafish as a model for studying kidney development, cilia and ciliopathies, human kidney disease pathology, and kidney injury/regeneration.
  3. Hermann Haller analyzes kidney vascularization in zebrafish, or how kidneys connect to the aorta and whole-body circulation during development, making blood flow possible. Understanding vascularization is an important first step in growing replacement kidneys.
  4. Romain Madelaine focuses on the nervous system. In humans, neuronal injuries and degenerative diseases are often induce permanent loss of smell or vision and muscular atrophy. Zebrafish can fully regenerate and restore sensory functions after injury and can help reveal molecular and therapeutic targets for alleviating or reversing age-related diseases.

C. Elegans

The short lifespan (12-18 days) of the worm C.elegans allows us to experiment with ways to slow down or even reverse aging. We also look at how stem cells maintain the capacity to become other cell types in the body. C. elegans are transparent and you can see their individual cells under the microscope. They primarily live in soil in temperate regions around the world, but in the lab, we raise them on agar media in petri dishes.

Three faculty at MDIBL study C. elegans:

  1. Aric Rogers uses C. elegans to identify the genes and environmental conditions that extend lifespan and delay the onset of age-related diseases such as diabetes, cancer, and neurodegeneration.
  2. Jarod Rollins studies how life-extending interventions, like restricting caloric intake, can help protect our cells and tissues from age-related decline.
  3. Dustin Updike looks at how stem cells maintain pluripotency, or the ability to become any type of cell in the body, work that will further our understanding of human fertility, wound healing, regeneration, and the formation of tumors.

Axolotl

Axolotls can regenerate almost any body part, including their limbs, brain, and heart; we study why humans form scars after an injury instead of regenerating new body parts like axolotls do. Unlike regular salamanders, axolotls do not go through metamorphosis (where they lose their external gills, and their lungs develop so that they can breathe on land). Instead, they stay fully aquatic their whole lives. Our axolotls are leucistic, meaning that their pigmentation has been changed so that we can see right through them — their organs, brains, and even the food that they eat can be seen through their skin.

Two faculty at MDIBL study axolotls:

  1. James Godwin explores the molecular signals from nerve and immune cells in the axolotl that underpin their resistance to scarring and active regeneration in hopes of helping human patients repair tissue after surgery, disease, or traumatic injury.
  2. Prayag Murawala tries to answer how tissue types such as the epidermis, bones, muscles, fibroblasts, nerves, vasculature, and immune cells in the axolotl coordinate after an amputation to perfectly restore the lost portion.

ATK

The African turquoise killifish (ATK) is MDIBL’s newest model organism. They have a very complicated breeding and hatching process that happens seamlessly in nature but is extremely difficult to simulate in a lab. Native to Africa, they live in ephemeral pools in semi-arid areas. The embryos can halt their development when the ponds they live in dry out and resume growth when the ponds fill up again. ATK fill a gap in aging research left by short-lived invertebrates, like C. elegans, and long-lived mammalian models, like mice. They display traits relevant to human aging, including vertebrate-specific genes, tissues and organs and a complex immune system, and can regenerate their caudal fin and heart tissue meaning it can be used to study how regenerative ability declines with age.

Together, our faculty advance the frontiers of regenerative medicine and aging with the help of non-mammalian model organisms. Armed with the secrets these organisms reveal, we are developing new strategies to enhance our natural ability to repair or regenerate damaged tissues and slow or reverse the degenerative changes that occur as we age.