Garbage Management as the Road to (Cellular) Immortality

Over at the Scientist, you'll find an interesting researcher's perspective on a topic that's come up here a couple of times: the relationship between the mechanics of cell division, garbage management, and aging. In essence we might look back at the origins of cellular life and decide that aging was in some way an inevitable adaptation in bacteria and other single celled life, stemming from the need to manage their garbage load. A cell, after all, accumulates garbage in the form of malformed proteins and gunk that cannot be broken down. If allowed to build up indefinitely, that garbage will destroy the cell. In order to preserve a lineage, cells therefore practice garbage management when they divide: one daughter cell is given all the garbage, allowing the other to continue pristine.

This works out well for single celled organisms - after all, they can just write off the occasional daughter lineage turned into a garbage disposal mechanism. It isn't so helpful for the multi-cellular organisms that later evolved. Now the garbage-cluttered cells can't just be written off: they're still present in the organism, being broken, inefficient, and gradually messing up the cellular environment. The ugly realities of cellular garbage gives rise to the garbage catastrophe in aging, and related issues, such as the age-related failure of garbage recycling mechanisms that have evolved to deal with multi-cellular existence.

The bigger picture is far more complex and less certain than the simple outline I provide, of course, so you might look back into the Fight Aging! archives for a longer introduction.

And here's that article from the Scientist, which ranges from personal account to speculation on information theory applied to cell biology to outline of aging research:

Unicellular organisms were thought to be capable of dividing forever, as long as conditions allowed: one generation begetting the next down through time - a sort of immortality. If unicellular organisms were like somatic cells, then they would age as they divide, reach the Hayflick limit, and die. It wasn't until the 1950s that researchers who thought about aging began to change their minds. It became clear that the daughter cells of some unicellular organisms seemed to rejuvenate, to start from scratch, while the mother cells accumulated the cellular aberrations that signaled aging. This pattern of aging was seen in such evolutionarily distant organisms like Saccharomyces cerevisiae, known as budding or baker’s yeast, and bacteria such as Caulobacter crescentus and Escherichia coli.


For me, that realization begged a more fundamental question, one that as biologists, we are scarcely allowed to ponder: Why do cells allow some mistakes to accumulate? If evolution is such a powerful process - one that finds solutions to all manner of problems - how could there be processes or problems that can’t be fixed? As I continued my research into aging and cell division, I couldn't help but think about how to categorize these "unfixable" problems like aging. Could there be a mathematical description that might capture and explain biology's fallibility?

Read the whole thing; it's an interesting line of thought.


I read this article a few days ago. I have to say that the arguments and reasoning seem logical. It looks like a very interesting avenue to follow. I have however been pondering the authors speculations concerning the following statement:

"Last, if aging is a consequence of Gödel’s theorem in biology and of the cell’s incompleteness, then aging is not a program but an inescapable fact. The quest for a cure to the aging “disease” will inevitably fail."

It was then that the discovery that it was possible to revert Somatic Cells into iPS Cells made me think that these speculations may be wrong!

Now, I'm no scientist or biologist, and I have only (in the last year; so I know not much), discovered just how far the field of ageing research has come but, and it is a big but; if the above statement was true, then surely the newly reverted iPS Cells would show signs of ageing?

I am aware that initially, this ageing was seen in iPS Cells. However, I have also recently seen (I am sure, but can't find the links now. Maybe it was Biotime), that it is possible to create iPS Cells that exhibit NO AGEING! That appear, to all intense and purpose, to be the same as ES Cells!

I am not saying that the authors speculations are wrong here;I am just pointing out that the scientists/biologists may have already found a way to remove the 'Mother cell junk', by finding the way to create iPS Cells. Could it be that they just haven't put two and two together?

Posted by: Andrew Simpson at October 13th, 2010 3:09 PM

My main problem with something like this, is how then do we get non-dividing cells(neurons) with very high metabolism able to function for countless decades(in some animals approaching 2 centuries)? We've to keep in mind that the majority of the energy spent by neurons is not used for self-repair but for their signaling function.

Or how about we take a look at insects, say termites. The workers can often live 1-2 years, the queen can last up to 50 years while laying thousands of eggs per day(iirc), so it should be extremely metabolically active organism... yet it benefits from over an order magnitude increased lifespan. How do we explain such massively long life span if there is some intrinsic barrier to longevity? e.g how can one member of the species gain dozens fold higher lifespan increase merely by being sheltered from the environment?

Also, what about negligible senescence organisms? Tissue analysis shows no perceptible sign of aging, iirc, even after countless decades.

From what I've heard many cells are able to tag and recycle most of the molecular machinery, and that which they cannot recycle can be isolated and made to accumulate. If this is so, it's only a few more steps to establish an export mechanism for said garbage.

As for genetic material garbage, iirc, many cells have the ability to distinguish foreign rna and dna, and dispose of it. I've not heard of ERC accumulation in more complex organisms, so it seems nature did find away around that particular problem(or I'm misinformed).

The only long term problem could be degradation of genetic information, which should be manageable if we introduce more robust error correction mechanisms.

Posted by: Cameron at October 13th, 2010 9:48 PM
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