Investigating the Agelessness of Hydra

Hydra are one of the few ageless species, or at least a good candidate for such: researchers have watched populations age for years with no signs of increased mortality rates or declining pace of reproduction. One might view these creatures as an incremental step up from bacteria or yeast: multicellular animals that can reproduce asexually via budding, and which are extremely proficient at regeneration.

One line of thought regarding the agelessness of hydra is that they simply consistently and relentlessly renew all the tissues in their body, which is accomplished by having very many stem cells that don't decline over time. Hydra might follow a strategy of eliminating the inevitable buildup of malformed proteins, aggregate waste products, and similar damage in individual cells by (a) sacrificing and then replacing damage-bearing cells, and (b) using the bacterial approach of moving as much damage as possible into one of the two daughter cells produced in any cell division. Since a hydra has no brain, any cell can be sacrificed at any time so long as it is replaced with an equivalent new cell - the whole organism can be replaced completely over any arbitrarily short period of time provided it can find the metabolic resources to do so.

There's nothing magical about making cell lineages last essentially forever. All bacteria do it, and even complex organisms like we humans are capable of it. There is, for example, the process that ensures that the first cells of a human child are biologically young and free from damage even though the parents bear decades worth of accumulated damage in their cells. It's also possible that hydra use an aggressive repair and renewal process of this nature, either when they bud or on an ongoing basis.

Aging doesn't happen because it has to, aging happens because it's almost always advantageous from an evolutionary perspective - that we age is an example of the success of the gene built upon the pain, suffering, and death of the individual who bears it. Though apparently this isn't the case for hydra, and many other types of life that are closer to what we might think of as self-replicating machines rather than populations of individual entities. One might argue that the big downside of individual entityhood is the need for brain cells that store data, and thus cannot simply be replaced at arbitrary times. Or perhaps one might argue that a necessary precondition for individual entityhood is a loss of the processes of aggressive regeneration and tissue replacement such that a thing like a brain might be able to evolve in the first place.

In any case, not everything that the aging research community works on is both interesting and potentially useful when it comes to intervening in human aging. Ongoing research into the biology of hydra is certainly interesting, but I'm dubious that we'll find anything that can inform us of a way out of our present predicament, the one in which we are aging to death. We and the hydra live in very different worlds, with very different requirements for success.

Here, for example, is a paper that steps into the stem cell biology of the hydra, but I don't think it tells us all that much in the end. The interesting matter to my mind is not really stem cell population size, or the ability to manipulate it by some genetic manipulation, but rather damage over time - breaking hydra agelessness by removing an aspect of their biology doesn't necessarily say anything meaningful about aging in general. Further, the release materials for this work overly stretch the case for the relevance of this work to human aging:

FoxO is a critical regulator of stem cell maintenance in immortal Hydra

"Surprisingly, our search for the gene that causes Hydra to be immortal led us to the so-called FoxO gene", says Anna-Marei Böhm, PhD student and first author of the study. The FoxO gene exists in all animals and humans and has been known for years. However, until now it was not known why human stem cells become fewer and inactive with increasing age, which biochemical mechanisms are involved and if FoxO played a role in ageing. In order to find the gene, the research group isolated Hydra's stem cells and then screened all of their genes.

The Kiel research team examined FoxO in several genetically modified polyps: Hydra with normal FoxO, with inactive FoxO and with enhanced FoxO. The scientists were able to show that animals without FoxO possess significantly fewer stem cells. Interestingly, the immune system in animals with inactive FoxO also changes drastically. "Drastic changes of the immune system similar to those observed in Hydra are also known from elderly humans", explains Philip Rosenstiel of the Institute of Clinical Molecular Biology at UKSH, whose research group contributed to the study.

"Our research group demonstrated for the first time that there is a direct link between the FoxO gene and ageing", says Thomas Bosch from the Zoological Institute of Kiel University, who led the Hydra study. Bosch continues: "FoxO has been found to be particularly active in centenarians - people older than one hundred years - which is why we believe that FoxO plays a key role in ageing - not only in Hydra but also in humans". However, the hypothesis cannot be verified on humans, as this would require a genetic manipulation of humans. Bosch stresses however that the current results are still a big step forward in explaining how humans age. Therefore the next step must be to study how the longevity gene FoxO works in Hydra, and how environmental factors influence FoxO activity.

I would say certainly and by all means do more work on the biology of hydra agelessness, but I don't think that these researchers have made any great leap of relevance to human aging here.

Comments

FOXO3 is known as a tumour suppressor.

More time should be spent researching FOXO3.

Posted by: RHW at December 26th, 2012 7:59 AM

FOXO1 is easy to activate, simply by inhibiting the pro-ageing IGF-1 signal pathway with myo-inositol--a simple seed sugar found in the beany/grainy diets commonly eaten by healthy 90-100 year olds. Anti-ageing researchers reveal both their nutritional ignorance and their remarkable laziness, by not investigating what oldies eat, for lessons for living longer, from those who have lived the longest!

Posted by: Dr Rob Peers at June 1st, 2013 2:42 AM

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