I’m just thinking out loud here.
If the cell was like a computer, it would need a processor, and it would need RAM. The nucleus would be the processor, and the endoplasmic reticulum would be the RAM (the Golgi Apparatus would be something like the network router, making sure proteins get sent to the correct places). Processes might be initiated in the nucleus, but some processes would be multi-step, requiring processes and callbacks to be registered in the endoplasmic reticulum. The need to conserve protein would force the adoption of paging (whatever the next process is could recycle protein from the last process). The need for protein conservation would probably also force the adoption of lightweight scripting languages (I mean lighter weight than base 4 DNA). DNA might be the machine language of living things, but a paging system that conserved protein (through re-use) would perhaps use larger molecules that worked at more than base 4. Evolution would encourage a system that was fast enough yet conserved protein.
There would have to be a garbage collector (as in the Java language – something that takes care of cleaning up variables, resources and processes after they are finished). For single celled organisms, the garbage collector would not have to be very good, so long as there was some kind of complete integrity check when the cell divided. Maybe the cell would forget to unregister a callback (or, in real-life, the forgotten unfolded protein), but why would it matter? After 30 minutes of eating, the single-celled organism divides, and undergoes some process that offers a real integrity check. The endoplasmic reticulum starts out clean again in the new cell. This is like a PHP script – no need to be terribly efficient about cleaning up the RAM while the script processes, because it is only going to run for 60 seconds. When it is done, all its variables will cease to exist, all the RAM it was using will be properly reclaimed. But problems arise for multi-celled organism that hope to live a long time. They need cells to stay in place and maintain a certain structure for a long time. The inefficient garbage collector that worked reasonably well for single celled organisms spells death for multi-celled organisms. And why wasn’t this problem addressed? Because rebooting is cheaper than building a perfect garbage collector that can last forever. It is cheaper for a multi-celled organism to have children than for that multi-celled organism to figure out how to be perfect in its use of its resources.
I recall when I was young I asked my dad why people got older, and he said it was because of genetic damage that builds up over time. That was the standard answer back then. My science teacher said the same thing. But of course, that can not be true. A 30 year old male and a 30 year old female can combine to create a child that is 0 years old. That is not possible if aging is a result of genetic damage. Assuming the egg cell and the sperm cell are exposed to the same genetic damage as the rest of the body, then the baby would be 30 years old the moment it is born, since it would be born with whatever genetic damage the male and the female had accumulated. No, to explain aging, we need a mechanism that allows two 30 year olds to give birth to a baby that is 0 years old. This article on aging raises the point:
How exactly does random damage to macromolecules translate into the reproducible and recognizable organismic phenotype we call “aging”? This issue was first raised in 1959 (2), but it still remains unsolved (3). Most often, free radicals or other noxious agents will damage macromolecules in a very stochastic, idiosyncratic fashion. It is difficult to understand how such a random process can lead to the significant and reproducible loss in tissue function observed during aging.
Aging can not simply arise from random accidents, otherwise the incidence of aging would appear as a bell curve, and on the extreme tips of that bell curve would be some individual humans who looked as if they had some age other than their chronological age. There would be the 20 year old with gray hair, dementia and osteoporosis, and there would be the 60 year old who is still able to play pro NFL football, because their body is really 20 years old. And, anyway, no one seriously suggests that the changes in the body of a 3 year old, as it becomes a 4 year old, arise simply from accidental genetic damage. There is clearly a process at work.
Reading on this issue, I get the impression that biologists currently have a model aging that goes like this:
1.) Senescence is used to end an individuals initial growth phase. Only some cells are suppose to enter senescence.
2.) Genetic damage causes other cells to undergo senescence.
3.) Once the body has largely stopped growing, cell death leads to loss of function, as the dying cells are no longer replaced.
About damage, the above article says:
Thus, we propose that aging ensues only when damage is extensive enough, and of a type capable of inducing a cellular response, which often results in either cell senescence or apoptosis.
But this really just moves the question: if aging is caused by senescence, then why does senescence cause aging? Why can’t the cells just live forever, and therefore why can’t the multi-celled organism (for instance, us humans) live forever? This bit is interesting:
There are considerable data indicating that, if a cellular response to damage is not activated, then cells can withstand a significant amount of damage to DNA without the organism showing signs of premature aging (10). Indeed, in most of the mouse models where caretaker functions have been inactivated, an increased level of DNA mutations has been observed as expected, but the mice fail to display an accelerated aging phenotype. For example, Xpc–/– mice accumulate up to 30-fold higher levels of DNA mutations than do their wild-type counterparts, yet there is no effect on their life span (11). A similar, though less dramatic result has been observed in the case of scavenging proteins. … There is a considerable accumulation of unrepaired mutations that has no deleterious effect on life span. … In contrast, mouse models in which the activity of gatekeepers (including telomerase, Wrn, Blm, ATM, or p53) has been manipulated do generally display an accelerated aging phenotype (16–20). In the cases of telomerase, Wrn, Blm, and others, the gene knockout results in generalized genomic instability, including not only double-stranded breaks, but also telomere shortening and/or stalled replication or transcription complexes, both of which appear to be interpreted by the cell as an unrepaired double-stranded break. As previously mentioned, this type of damage leads to activation of a response that culminates in cellular senescence or apoptosis (4). From these data, we must conclude either that genomic instability (but not mutations) plays a role in aging, or that longevity is related to the cellular response of the cell to such DNA damage.
So the cell can take a lot of genetic damage, with no impact on life span, but a few key gatekeepers are needed to watch over things.
Most cells can only reproduce a limited number of times, even when you remove them from the body and cultivate them under ideal circumstances in a petri dish:
Cells divide vigorously and can often be subcultivated in a matter of a few days. Eventually, however, cells start dividing slower, which marks the beginning of Phase III. Eventually they stop dividing at all and may or not die (reviewed in Hayflick, 1985; Hayflick, 1994). Hayflick and Moorhead noticed that cultures stopped dividing after an average of fifty cumulative population doublings (CPDs). This phenomenon is known as Hayflick’s limit, Phase III phenomenon, or, as it will be called herein, replicative senescence (RS).
The limit depends on the type of cell and the species it is from:
Early results suggested a relation between the number of CPDs cells undergo in culture and the longevity of the species from which the cells were derived. For example, cells from the Galapagos tortoise, which–as described–can live over a century, divide about 110 times (Goldstein, 1974), while mouse cells divide roughly 15 times (Stanley et al., 1975; Rohme, 1981).
But some cells are immortal:
Exceptions exist and certain cell lines never reach RS. These are said to be “immortal” and include embryonic germ cells and most cell lines derived from tumors, such as HeLa cells (Brunmark et al., 1986; Chen and Yu, 1994; Pera et al., 2000). Some types of rat cells have also been claimed as capable of evading RS (Mathon et al., 2001; Tang et al., 2001).
And, of course, in recent years, scientists have figured out ways to roll back specialized cells and make them more like embryonic stem cells.
As things stand now, if one of your cells suffers a certain kind of damage, it will become senescent, and then it becomes a risk for cancer. If it accumulates more damage of a certain type, it will eventually develop into cancer. So why does the body allow such cells to exist? Why not kill all such cells? The most obvious answer to that is that, once the body has stopped generating a lot of new cells, it can not afford to kill off all of its existing cells. It needs to hang on to them, with the hope that you, damaged as you are, can live long enough to raise children.
Here is an avenue I’d like to research (perhaps some day I will switch careers): what if all senescent cells in your body were forced to die, and your body was allowed to grow new cells? This assumes that science develops a reliable method for getting particular genetic commands to one’s cells – but there are experiments with using genetically engineered viruses that are getting closer to that goal.
I’ve read that senescence is unique to vertebrates. To put that another way, senescence is unique to creatures that have central nervous systems. Lately I’ve been wondering if the nervous system is the main reason our bodies do not already do what I’m suggesting – why not kill off all the senescent cells and replace them with younger cells? While it would be great to have new muscle cells and new bone cells and new kidney cells and new colon cells and new skin cells, it generally would not be a good thing to casually kill off nerve cells. That is where vertebrates store everything they’ve learned. Tadpoles spend several days learning how to swim, no doubt it would be suicide for an adult frog to suddenly forget how to swim in water – evolution will not allow the emergence of a vertebrate that loses crucial skills as an adult. But humans are in a unique situation. We can afford to retire from life – we already do so. We could retire from life for 4 or 5 years, and be helpless, and have nurses take care of us. We could afford to forget how to walk and talk and eat – some already do this when they are old. But the way things work now, when humans reach that point, they usually only go a few more years and then they die. It is fascinating to think where we will be when we know how to order our cells to die off and then renew. Then we would retire from life for a few years, relearn skills, and then return to life, made young again. We would not die, though there would be a sorrow like death, as we would probably suffer massive amnesia, depending on how many of our nerve cells renewed. Our friends would regret the disappearance of the person they knew and loved. They would have to learn to live with the fact that the soul is transitory and does not last, even as the body lives on forever.