The Hydra, a small freshwater invertebrate, is an advantageous model organism for regenerative biologists. Named after the serpent from Greek mythology that grew two new heads for each one cut off, this tiny, jellyfish-like creature holds within its genomic code the key to biological immortality. Hydra are unique because their stem cells exist in a continuous state of renewal. Kept safe and in isolation, these organisms show no signs of aging. Outside the lab, the only real threats they face are predators, weather extremes and disease. Ever resilient, Hydra can survive dismemberment by regenerating lost sections of their bodies. Chop a Hydra into segments, and each segment will become a new Hydra. Blend one up, and you’re left with a soup of cells. If you ball up those cells using a centrifuge, they reorganize, eventually forming a new Hydra. Assistant Professor Celina Juliano, Department of Molecular and Cellular Biology at the UC Davis College of Biological Sciences, and her colleagues are probing Hydra stem cells, hoping to find clues to the organism’s regenerative capabilities and longevity.

The eternal embryo

Hydra are named after the famed serpent of Greek mythology which grew two new heads for each one cut off. This ancient water jar depicts the Lernaean Hydra battling Heracles (Etruscan, c. 525 BCE). ﻿J. Paul Getty Museum Stem cells form the foundational building blocks of an organism’s body. During embryonic growth and development, stem cells differentiate, becoming various cells throughout the body. In many organisms, stem cells lose their ability to replace dysfunctional cells with age. Hydra stem cells are different. “If the animal has very powerful stem cells—because stem cells are the cells that give rise to all of your tissues—then you can regenerate very well,” said Juliano. “They sometimes call Hydra the eternal embryo.” Continuous stem cell renewal is a major focus of Juliano’s research. However, this doesn’t fully explain Hydra longevity. To uncover this mystery, Juliano is interested in how Hydra maintains its genome despite undergoing a large number of cell divisions. “The Hydra renews itself all the time, but just renewing yourself isn’t enough,” said Juliano. “The genome itself has to be faithfully propagated.” A Menagerie of Model Organisms What can a worm or fish tell us about the human body? When it comes to biology, quite a lot actually. In many cases, scientific inquiry begins with our relatives in the animal kingdom.

Why don’t Hydra age?

Juliano and her colleagues in the Juliano Lab are searching for the genetic elements that help prevent biological aging in Hydra. They’re particularly interested in transposons, which are also called “jumping genes.” In organisms that age, such as humans, transposon expression is kept in check by a variety of genetic pathways during youth. As time plods on, aging cells lose control over transposon repression. Uncontrolled, these jumping genes bounce around the genome, replicating, proliferating and inserting themselves into the genome like unhinged saboteurs. Some believe transposon expression plays a role in aging, but why the human body’s cells eventually lose control over this pathway is still a mystery. Hydra cells never lose the ability to repress transposons. “I wouldn’t say it’s the magic bullet of why Hydra doesn’t age,” said Juliano. “But this is one thing we’re interested in, how transposons are repressed in adult stem cells.”

The lack of aging in Hydra, scientifically termed non-senescence, is due to the seemingly endless ability to regenerate stem cells. ﻿Stefan Siebert/Juliano Lab