The animal that wouldn’t die

Hydra. Photograph by Przemysław Malkowski, distributed under a CC-BY 2.0 license.
Hydra. Photograph by Przemysław Malkowski, distributed under a CC-BY 2.0 license.

Understanding aging and how it affects the lifespan of an organism is a fundamental problem in biology that is of great interest to our society. During the last decade, an incredible amount of research has been published trying to understand aging processes, unraveling what factors accelerate or decelerate this process in several animal models (worms, flies, mice, etc…). In the majority of those studies we all assume that aging is a universal feature in nature that affects all animal species. Quite surprisingly, there is one animal that breaks this rule: the cnidarian Hydra vulgaris. It may sound like science fiction, but this small tubular polyp has been reported to live unlimitedly if the environmental factors are good enough 12.

The apparent immortality of Hydra Vulgaris was first reported by Prof. Daniel Martinez at the Pomona College in Claremont, California, in 1998 (1). He analyzed mortality patterns of different groups of H. vulgaris for four years surprisingly not finding evidences of aging or mortality whereas other cnidarians die after 3-6 months of life. Although there has been some controversy 3, those same findings have been repeated by other groups, even finding how some genes can regulate this process 4. Thus, it is pretty clear that Hydra Vulgaris seems to live forever… but how is that possible?

The enigma of the everlasting Hydra is being solved in the latest years. The biological reason behind this unique potential to escape aging and mortality is actually simple: this cnidarians have adopted a life cycle in which proliferation and population growth occurs exclusively asexually by budding. This means that individual Hydra organisms do not proliferate sexually (two Hydra parents contributing with genetic information) but they do it asexually (the new Hydra generated is genetically identical to the single parent). The budding asexual mode of reproduction is highly demanding for these animals and requires each individual polyp to maintain a huge number of undifferentiated proliferating cells to allow the generation of new individuals. These undifferentiated cells are stem cells, which can virtually be converted into any cell type of the animal and in Hydras constitute almost the 10% of the total number of cells in their body 56.

This incredible stem cell system of Hydra, which occupies almost all the central body column of the organism, possesses a continuous self-renewal capacity. Thanks to this indefinite expansion capacity, the high number of stem cells fastly and relentlessly renews all the tissues in their body, replacing all cells in the organism every twenty days. This constant renewal process helps to avoid individual cellular damage and genetic instability that is normally acquired over time in aged differentiated cells of other organisms (ours included!). An old cell in Hydra is fastly replaced by a new one coming from a stem cell, and that new cell will be replaced soon again by another one, repeating a cycle that continuously renovates aged cells avoiding aging in this animals.

Thanks to this outstanding stem cell system, Hydras possess another remarkable feature highly related to immortality: regeneration. The first regeneration experiments in Hydra are actually quite old, starting in the eighteenth century when Abraham Trembley (1710-1784) discovered that after cutting the polyp in half, each part could produce a complete and separate healthy new animal. Even more, recent experiments amazingly show that one can disaggregate one Hydra into separated and isolated cells, put all those cells back together and observe that a new animal is formed in the next few days 7. Again, it sounds like science fiction, but it is not. It is all due to the continuous production of stem cells in the adult tissue and the maintenance of cellular polarity in the differentiated cells (i.e., each differentiated cell knew where it was before disgregation). These features allow the cells to reorganize and create new cells where needed, being able to create in the end a new organism.

This is all truly exciting. However, since Hydras are really simple animals, there is an obvious question arising here: are any of these investigations relevant to human aging research? The answer is: they are. Hydra shares many genes with humans and deciphering which ones are important for maintaining Hydra’s immortality can reveal new genetic pathways implicated in human ageing. Following this idea, the group of Dr. Thomas C.G. Bosch in Kiel (Germany) published two years ago an article in PNAS in which they examined the genetic characteristics of Hydra’s stem cells, discovering a new link to ageing in humans. Boehm AM et al found that the gene named FoxO plays a decisive role in the maintenance of stem cells and therefore its activity controls Hydra’s immortality (4). Surprisingly, FoxO has been found to be particularly active in centenarian humans and its activity is positively correlated with longevity in many species. The mechanisms by which FoxO extends lifespan have remained elusive but thanks to Hydra investigations the authors propose that FoxO controls human stem cell populations controlling old-cell renewal in adults, following the theory that organismal aging is a consequence of stem cell senescence (2).

What is most interesting about this research is that aging is not solely a passive degenerative process that occurs while time passes by but it’s in fact actively regulated by genetic pathways. Understanding the molecular basis of immortality in Hydra and manipulating these pathways could offer the opportunity to find new human age-related genetic pathways that could help to combat age-related disorders. The first scientist reporting Hydra’s immortality, Prof. Daniel Martinez, has been awarded a few years ago with a $1.26 million grant to study mechanisms related to aging in Hydra. So a lot of progress is yet to come!

References

  1. Martínez DE (1998) Mortality patterns suggest lack of senescence in hydra. Exp Gerontol 33(3):217-25. doi:10.1016/S0531-5565(97)00113-7
  2. Boehm AM, Rosenstiel P, Bosch TC (2013) Stem cells and aging from a quasi-immortal point of view. Bioessays. 35(11):994-1003. doi: 10.1002/bies.201300075.
  3. Estep PW (2010) Declining asexual reproduction is suggestive of senescence in hydra: comment on Martinez, D., “Mortality patterns suggest lack of senescence in hydra.” Exp Gerontol 33, 217-25. Exp Gerontol 45(9):645-6. doi: 10.1016/j.exger.2010.03.017.
  4. Boehm AM, Khalturin K, Anton-Erxleben F, Hemmrich G, Klostermeier UC, Lopez-Quintero JA, Oberg HH, Puchert M, Rosenstiel P, Wittlieb J, Bosch TC (2012) FoxO is a critical regulator of stem cell maintenance in immortal Hydra. Proc Natl Acad Sci U S A 109(48):19697-702. doi: 10.1073/pnas.1209714109.
  5. Bosch TC, Anton-Erxleben F, Hemmrich G, Khalturin K (2010) The Hydra polyp: nothing but an active stem cell community. Dev Growth Differ 52(1):15-25. doi: 10.1111/j.1440-169X.2009.01143.x.
  6. David, C. N. and Plotnick, I (1980) Distribution of interstitial stem cells in Hydra. Dev Biol. 76(1),175–184. doi: 10.1016/0012-1606(80)90370-X
  7. Bosch TC (2007) Why polyps regenerate and we don’t: towards a cellular and molecular framework for Hydra regeneration. Dev Biol 303(2):421-33. doi: 10.1016/j.ydbio.2006.12.012

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