Less turnover. Less replacement.

Aging is mainly tissue attrition. Hence regeneration research is where time, money and energy are best spent when it comes to solving the puzzle of aging. Because the ability to regenerate is often – but not always – found in species with negligible senescence. Coupled or not with slow growth.

There is a certain arrogance in the medical field that humans don’t have anything to learn from other species, especially simple ones. And yet penicillin, a substance manufactured by a fungus to defend itself from bacteria – both unicellular organisms -, saved many human lives, humans which are both complex and multicelullar. In a similar way, we could learn a couple of things from primitive multicelullar organisms capable of something more than regenerating limbs.
Regeneration ability decreases from the young to the old and from the simple to the more complex species. And in order to implement complete rejuvenation in complex humans, understanding how simple organisms regenerate is crucial for two reasons:
1. Simple organisms are able to completely regenerate themselves as adults, some of them being able to reaggregate their bodies after having their cells separated (!) – this could be the inspiration for new products and services that could allow complex species like mammals to do the same.
2. Comparing the two types of regeneration – complete in simple animals and partial in complex ones – may aid in implementing new technologies in people or may explain why regeneration from simple animals can’t be implemented in complex ones.

While regeneration can take place at any level from molecules to organisms, I will refer here to the regeneration of tissues and organs.

Just like normal growth, regeneration must be regulated by the organism at its initiation, during the process and at its completion. The formation of scars is an example of incomplete regeneration where the process is not taking its normal course of creating a new tissue with the same shape and function as the previously injured one. And regeneration can certainly take place without the proper stop e.g. an axolotl that regenerates two tails instead of one. If the organism’s polarity is not immediately re-patterned, regeneration can start in the wrong place e.g. ectopic tail regeneration in salamanders.

During regeneration, cells from simple and complex animals do two things – albeit in different ratios:
1. They reorganize themselves by determining their location relative to other cells and if necessary, move around until the polarity of the organism is readjusted (more or less).
2. They differentiate while dividing so that the organism regains its previous shape, size and if possible, function.When differentiation can’t take place anymore for lack of the appropriate signals, compensatory hypetrophy sets in where the organ increases to the former size without compensating in function too – a pattern seen again and again in the way human beings age.

 

Simple animals regenerate by morphallaxis – a situation where cells rather reorganize themselves than commit to differentiation. These primitive animals – corals, sponges, hydras – don’t have much differentiated tissues anyway. Their bodies consist of a couple of layers of cells, so reorganization is more important than differentiation for lack of true tissues. Check out morphallaxis in the video below by watching a timelapse of reaggregation in sponges – an example of regeneration in primitive multicellular organisms that mainly repattern themselves through morphallaxis.

 

On the other hand, complex animals regenerate by epimorphosis – a phenomenon where a small group of stem cells form a blastema which later differentiates itself into the necessary cells. Reorganization of initial cells takes place in complex animals as well, but to a smaller degree.

In order for epimorphosis to take place, a supply of stem cells must be available and the former must be capable of differentiation. When these two conditions are not met, the organism tries to makes do. The elderly repair their injuries through the formation of extensive scars and compensatory hypertrophy, where the cells increase their diameter instead of their number. And when not even compensatory hypertrophy is possible anymore – because that necessitates a minimum number of capable cells – organ atrophy sets in until the very end.

Check out epimorphosis in the video below where regeneration takes place mostly by differentiation in a leopard gecko pet that lost its tail.

Regeneration is growth plus differentiation plus restoring polarity in the organism. What primitive animals do better than us is restoring polarity even when the body has been separated in its constituent cells. And what complex animals do better is differentiation, especially when young and healthy.

Anca Ioviţă is the author of Eat Less Live Longer: Your Practical Guide to Calorie Restriction with Optimal Nutrition ,The Aging Gap Between Species and What Is Your Legacy? 101Ways on Getting Started to Create and Build One available on Amazon and several other places. If you enjoyed this article, don’t forget to sign up to receive updates on longevity news and novel book projects!

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