TL;DR the greatest risk to a long-lived organism is cancer, when cells start to reproduce incorrectly. To prevent this, not only you need a method to supply fresh stem cells to all organs but also a "check" (almost certainly an enzyme of some kind) to kill off runaway cells, to be replaced by core-produced stem cells. This mechanism does not protect the core itself: if it's overused, to the contrary, the core either withers away, or kills off the rest of the organism.

It would be a basic biologic protection system. The "core" would need to produce a sort of totipotent stem cells and keep the blood saturated in them. The stimulus to produce such cells would then be the depletion of such cells in the blood.

At the same time the organ has to "retire" the cells grown too old and weak, and implement some kind of regenerative check on all cell lines to prevent random mutations from devolving into cancers (see "integrity check", below). And/Or maybe the Hayflick limit for "normal" or fully grown cells is much lower, so they don't have the time to degenerate but rather go into apoptosis - they live fast, die early and leave a beautiful corpse.

(So another difference of the Evas would need to be that their cells are on average much "younger" than a normal human's).

If we make this work this way, at least two awkward limitations follow.

One: reproduction becomes incredibly complicated, unless the core allows for a "grace period" before going active (maybe just after puberty?) and pregnancy shuts down the core enough to let a foetus grow and mature to term undisturbed (a newborn will have a DNA which isn't the same as the parent's, and the DNA check routine would kill it at a very early stage).

Two: the core itself cannot "self-check". Immature core cells are immature core cells, mature core cells are totipotent stem cells. In some ways, the core is a stabilized tumour, and in some other ways it behaves like a liver. It can have some limited regeneration capabilities, but the reproduction of immature core cells is a very, very touchy business - triggering it too often or too fast is likely to make the whole process go awry in some terrifying way. Most likely, the core goes fully cancerous and starts eating up the rest of the organism.

(It might be possible to have an Evangelion regenerate by pumping him full of some metabolism-slowing drug, and keeping him hypothermic and in a coma, so the core doesn't exceed its design specs. Or transplanting a large enough compatible core chunk).

Hypothetical core development

• at birth: the core begins to grow (e.g. somewhere under the heart).


• age three to fifteen: the core grows but is otherwise nonfunctional. Normal body growth can take place, bones are digested and remade longer, new organs can develop and mature.


• age fifteen to eighteen (more or less): the core activates and takes some roles of a human's Major Histocompatibility Complex, plus some really wicked, DNA-based integrity check system. Some biological effects and possibly a shock occurs. Also, any damaged or mutated tissues are swiftly killed and replaced, possibly triggering some form of septic shock or rhabdomyolisis. Bottom line: not all Evas survive their coming of age.


• age eighteen onwards: the core has the blood saturated in "repair workers". Most large scale cellular damage can be repaired. Actually, large damage to the brain will be repaired but leave the victim with severe mental effects, amnesia being the least.


• during pregnancy, pregnancy hormones shut down the core and floating cells so that they don't "think" it's a good idea to do something for that poor swollen uterus full of fluids and who-knows-what. Downside: a pregnant Eva is much more vulnerable than a human, since it has next to no regenerative powers (they'd be superfluous with a working core). As a stopgap measure, a wounded pregnant Eva might immediately abort the pregnancy and return to "full defense mode".


• normally, the core awakens periodically and tops up the reservoirs at leisure, and it always filters out weakened stem cells from the bloodstream, destroying them and using the raw materials to build new cells.


• a large systemic shock (e.g. loss of a limb) sends the Eva in a regenerative coma, with metabolism reduced to the bare minimum and just enough circulation to keep repairs going. The core goes into low-level, long-term activation and wears out a bit, eating into its own regenerative reservoirs. It's important to keep the Eva well fed, otherwise his chances on recovery depend on body fat and muscle reserves. In ancient times, fat was synonym of health; for Evas it is still so.


• in case of multiple, repeated activations, while the rest of the body gets "iguana-like" regeneration, the core itself has "lizard-like" regeneration, and the mechanism goes awry. As a result, the Evangelion dies, not too horribly since the heart is the first to go.


• lower genetic diversity between Evas allow easier core transplants between them.

The answer is in Genesis: The Tree of Life.

https://www.biblegateway.com/passage/?search=Genesis+3&version=KJV

3:22 And the Lord God said, Behold, the man is become as one of us, to
know good and evil: and now, lest he put forth his hand, and take also
of the tree of life, and eat, and live for ever:

3:23 Therefore the Lord God sent him forth from the garden of Eden, to
till the ground from whence he was taken.

God expelled Adam and Eve before they could eat from the Tree of Life. But Lilith remembered. Also she knows a lot more about angels than Cain does. She snuck them back in to Eden and got out with a fruit from the Tree of Life.

The fruit regenerates itself. The immortality core in the Evangelons is a bite from this fruit. Each Evangelon takes a bite as a rite of passage - gaining prohibited immortality and scorning the command of God. This bite of fruit integrates itself into the being, granting divine immortality. But it is not the fruit and it will not regenerate itself. If it is damaged somehow or taken from the Evangelon, that being becomes just another son or daughter of Adam.

LSemi went all around the answer without actually being specific.

To 'regenerate' a cell means the cell has to die. If the cell itself is immortal, it would never die, and thus there would be no need to regenerate it. Otherwise, one risks the inevitable cancerous growth, where regeneration occurs uncontrollably without concurrent cell death. If the cell does die, and needs to be regenerated, then this process must be very tightly controlled for cancer and mutations. That is, every regenerated cell must be identical to the original, and must only be regenerated upon the death of the original cell.

The weakest link in immortality is the possibility of the cells mutating and the DNA degenerating. The original organism may be immortal, but in subsequent regeneration, will this immortality be lost? If there is one immortality organ controlling the regeneration of all other organs, then one of the functions of this organ would be to ensure the quality and purity of all of the reproductions, with the ability to terminate them should they deviate from specs, or become cancerous. That is, this organ would ensure that all regenerated cells would be exact duplicates of the original. However, this quality control can not be absolutely assured if the controlling organ itself can be regenerated. What enforces the enforcer? By what mechanism can it be assured that the regeneration of the regenerating organ is never compromised?

By ensuring that the regenerating organ is always the original copy, and that the regenerating organ can not itself be regenerated, immortality can not be lost through mutation or cancer.

Different DNA

These Cruel Angels actually have two sets of DNA. One for the majority of themselves, and a second for the core. The core is only able to replicate the first set of DNA. Due to the complexity of the core's DNA, or maybe as an evolved safety measure against core cancer, the core cannot replicate its own sequence. The core only grows during gestation. It is full sized and stops shortly after the Eva is born.

Or slightly differently, the core can take in other sets of DNA and replicate it, but not its own. Then the core might be valuable to ordinary Humans, or there might be a way for Evas to regenerate each others' cores.

It is a design limitation

The core was included in the design of Evas and was responsible for their long lifespans and regeneration. Explanation of why the Evas have a core and other humans do not is a bit of a mystery.

However, just as normal human cells have a Hayflick Limit limiting cell to around 50-70 division due to the shortening of the telomeres, the DNA in the core likewise has a division limit, based on something similar to regular telemores, but enough different that the core cannot repair its own.

Cells in the core are also limited to 50-70 divisions, but the cells in the core have a longer life cycle than typical cells. This longer-life design is inappropriate for the human overall, as this also results in a comparatively slow metabolism.

Once the core cells reach their own Hayflick limit, the body dies. It turns out that the body is not really immortal, it is just capable of a very long lifespan.

When I completed this, I saw it as actually similar to the answer given by Xavon_Wrentaille

It is already dead.

This has precedent - the lens of the human eye "dies" during development, and discards all internal organelles so that it is transparent.

Why would your core require this? The vast majority of the core is a chitinous mass, that contains, guides and separates the individual components that allow for regeneration. If this protective sheath were still alive, then it would continue to grow and regenerate, eventually cutting the rest of the body off from regeneration.

On the other hand, if the different regenerative components - producing telomerase, platelets, et cetera, to rebuild tissue damage - were to come into contact then they would undergo unconstrained growth, and engulf the Evangelion in a cancer-like mass that prevented it from being able to move or act.

The core only works while undamaged

Being a complex organ, the core stops functioning entirely when it's damaged. Think of a clockwork. Every part has to play together in order to accomplish a goal. If you remove even one cogwheel the whole contraption stops working. Now for your core, this would mean the following:

• It can regenerate organic matter


• It stops regenerating once it's damaged


• It can never regenerate itself since it can't regenerate at all once damaged

However, you wrote:

It cannot repair damage done to it, which reduces the Evas regenerative ability.

Keep in mind that this solution stretches the word "reduce" quite a bit

It certainly reduces the ability, but only to zero. If you want a damaged core to function (less efficiently), I would suggest a different approach like the "different DNA" answer.

It has it's own circulatory system, so that if the heart is damaged, it can be repaired without a beating heart. This circulatory system is dormant until needed at which point the organ secretes from a 'bladder' the repair cells to the damaged area. However, this circulatory system does not feed back to the organ itself.

Cells are produced and stored in this bladder until needed. This allows for the quick delivery of a large amount of repair cells. The bladder can repair itself since it is full of repair cells. However the organ only has a small number of these cells at any given time as it sends them to the repair bladder, any repairs to the organ itself are slow.

The cells flow towards the bladder after production, if it detects damage, it repairs it right away in the organ itself. Think of it like a tree, the leaves produce the cells, they flow through the stem, to the branch, to the trunk. If the leaf is cut off, there is no path for the cells to move backwards. If a repair cell happens to have just been produced and is still there when the damage occurred, then it can repair the leaf.

When 1/2 of the repair cells are destroyed, it takes twice as long for the bladder to fill. It solves the issue of 'where does the matter come from' when repairing. It's not infinite, it slowly builds over time and is stored in the repair bladder. Too much damage to the body would require a longer period of time to heal, when low in cells it only repairs the essentials for life. This idea leaves open the possibility of medical advancements that would allow surgeries to manually distribute these cells back to their producers for repair...same for organ transplants I suppose.

BTW decapitation is game over...there can be only one.

I'd throw in some already existing biological tissues and organs that might be used as an inspiration.

• Teeth. Our whole problem with dentists arises from the fact that dentine tissue cannot be re-created by a somewhat mature organism. A fetus "knows" how to create teeth, it has cells that develop into teeth tissue, but more or less aged specimen does not have those progenitor cells anymore.


• Thymus. The organ plays a role in "bootstrapping" immune system, but it is apparently of little use (citation needed) for a mature organism. Hence its tissue are slowly replaced by fatty tissue. One might speculate that the decrease of immune response in elderly people has something to do with it, but I digress.

To summarise: either the organ is actually dead / has no progenitor cells for its tissue in adult organism, or the organ is not needed anymore in adult organism and is slowly replaced with inert tissue.

For the second option, the actual Sci-Fi effect would be produced by some other cells that the organ produces, that live in the body more-less indefinitely, but don't really need to be produced in the later life, causing the Sci-Fi effect to detoriate with age. The analogy might be blood cells, such as B-cells (immunity) or erythrocytes (oxygen transport), if you factor out that erythrocytes are short-lived.

This is a fun question to think about.

Copying and the Hayflick Limit

Generally what stops humans from being immortal, well at least one of the mechanisms, is whats known as the Hayflick limit. Basically its a limitation to the number of regenerations a cell line can take, before it experiences programmed death. Theres a good reason for this. The more a cell reproduces, as in copy, copy of copy, copy of copy of copy, the more 'noise' is introduced to the genome in the form of mutations, inefficiencies and ultimately, cancers. Cancer in fact largely works by disabling the hayflick limit and thus becoming immortal (Or at least until it kills the host, or the hosts immune system kills it.)

So how dow we work this into our immortal 8ft tall guys with a core?

Mother cells and Stem cells

The cores job is to store a pristine copy of the genetic blueprint of the human, as well as a reserve of stem cells that can be deployed to replace cells getting close to the hayflick limit. The stem cells are always first generation copies, because at the center of the organ is a reserve of mother cells that never die and when they divide there is always one of the divided cells that keep the original genome. But if these cells are destroyed, they will not grow back, because then the mother cells would not be original copies anymore. The mechanism that ensure the mother cells are original also ensures they can not grow back. (Note, Mother Cells are not a thing in IRL biology)

The Blood-Core Barrier

The organ features a blood-core barrier around the mother cells that only allows a heavily filtered set of blood components in, as, much like the brain which also can not reproduce its cells (mature neurons dont really have a reproductive capability), no immune system exists in there, this is to prevent auto-immune disorders attacking the core. This is not really a problem as the blood-core barrier doesn't allow any cells in except red blood cells and since red adult blood cells ALSO don't have reproductive capacity they can't be hijacked by viruses. The downside of this is a rupture or damage to the barrier makes the core extremely vunerable to infection.

Putting it together

As long as the organ is uninjured, and the mother cells are protected from infection or rupture, the core can generate stem cells forever to replace dying cells elsewhere in the body. If the core is injured however, particularly the reserve of mother cells, all bets are off, and even with close modern medical care, the patient can only reasonably expect to live another 50 or therabouts years, as now their cells will age , die, and mutate just like the rest of us.

Caveat

I'm a little hazy on the exact way mother cells can create new stem cells without the mother cells themselves being prone to the hayflick limit or copying errors, but perhaps they have a unique mode generating the stem cells I guess.

The organ requires a specific diet to operate and without that plant it cannot regenerate the body or itself--it dies and the body becomes mortal.

The concept is adapted from something in Larry Niven's Ringworld I can't believe how many topics on this site have similarities to ringworld.

What I recall of his explanation was that the human appendix had evolved to process a certain type of now-extinct plant (something similar to sugar cane). When humans started eating this plant at 20ish years of age they evolved from an irresponsible, ignorant nymph stage into an adult stage and became intelligent, strong and long-lived. After this change they lived almost exclusively on this plant.

Since the plant went extinct, we have never been able to get out of the nymph stage and our bodies are exposed to all these horrible age-related problems including extremely early death.

When the original species that colonized earth re-located us they couldn't believe what we'd accomplished considering we were stuck in the "nymph" stage.

I haven't read this for like 40 years so I'm probably quite inaccurate.