From: Phil Osborn (philosborn@altavista.com)
Date: Sun Oct 14 2001 - 22:10:34 MDT
A few years ago, Scientific American ran a piece on mitochondrial aging, the gist of which was that as one aged, the population of mutated and generally defective or inefficient mitochondria increased in percentage. Consequently, the general efficiency of energy production in the cells declined.
I had a couple of problems with that right off. Not that I challenged their data, just that it raised some obvious questions. How is it that the mitochondria in the cells in general mutates so much while the mitochondria passed on in the egg does not? (If it did, then each generation would have more defective eggs, which does not generally appear to be the case.) Secondly, why is it that the proportion of defective mitochondria increases? What happens to select for them as opposed to selecting for cells with the best mitochondrial genes?
(For those unfamiliar with mitochondria, they are the main energy producers in the cell. They have their own DNA, totally independent of the main DNA in the nucleus, and they are inherited strictly from the mother via the egg. Mitochondria have certain inherent problems due to the fact of the high energy chemical transactions that they specialize in, mainly mutations or other damage from reactions that get out of control. In a given egg, there may be hundreds, I believe, of mitochondria, each with its own DNA. Actually, most of them will be direct descendents of a single mitochondria back down the reproductive line, and so will share the same DNA. When the egg is fertilized and begins dividing to form an embryo, the proportions of different mitochondria that end up in the new cells is purely random, as far as we know, meaning that even "identical" twins may have very different strengths and weaknesses, as conceivably the best DNA could, for example, have ended up in one organ in one twin and a different
one in the other.)
One hypothesis that I arrived at finally, which I would appreciate comment on, is that a higher level of energy production for a cell means a shorter doubling time and consequently a faster arrival at the Hayflick limit. I.e., assuming that cellular reproduction occurs in response to a signal and that the response likelihood is dependent upon available energy - which may not be the case, but it does seem reasonable - then those cells with an abundance of energy would be more likely to respond. Thus, over time, cells that have poorer mitochondria tend to dominate, simply because their telomeres are longer, having not divided as many times.
If this is the case, it is interesting to speculate upon the effects of different populations of mitochondria. If one had only mitochondria of a particular kind, how would this influence lifespan, as opposed to having a variety of widely varying mitochondria, ranging from high output to useless. A person with a wide variety of mitochondria might be expected to age rather dramatically as various cell populations with varying proportions hit the Hayflick limit early or late. A person with only one breed of mitochondria could be expected to age uniformly, with less likelihood of catastrophic organ failure.
Finally, with the cell itself, there appears to be a natural selection in favor of bad mitochondria. The most active mitochondria will also be those most likely to suffer damage from stray electrons, etc.
Comments? References?
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