Hi folks…  I answer questions for the Howard Hughes Medical Institute Ask a Scientist program, and it occurred to me that perhaps people here, who tend to be pretty well educated, would be interested in reading and discussing some of the questions.  So, in a pilot sort of way, I thought I’d try an experimental post along these lines.  (Quick disclaimer: This is not for the purpose of giving medical advice.)  Today’s topic is about the aging of cloned animals.

Some cloned animals seem to age faster than normal.  If the clone cells “remember” the age of the mother, the process of DNA replication through mitosis is less and less efficient (my limited understanding.)  She wanted to know why single-celled organisms do not eventually produce less perfect copies, as differentiated body cells would, because they are also reproducing by mitosis.

“Answer” on the flip…
For some background information, I recommend the web page http://senescence.info/causes.html particularly the third section, animal cloning and aging.  The results summarized there seem somewhat inconsistent, such that in some but not all cases of cloning has accelerated aging been observed, and the initial hypothesis for the cause of accelerated aging–telomere shortening–does not appear correct.

Baker’s yeast is the single-celled organism most intensively studied on topics of aging.  There is a significant difference between a multicellular organism and a culture of unicellular organisms.  The effects of aging on single cells seem to be sporadic or statistical to some degree–if you were to follow a lineage as time goes on, the number of age-related problems increase, but in a unicellular population, the phenotypically ‘aged’ cells are selected against and gradually disappear from the population (whereas in a multicellular body, the aged cells hang around for a while, and sometimes are not easily replaced when they die).  

With unicellular organisms, the cells that are lucky and remain healthy reproduce the most, and this leads to a steady-state situation where some fraction of cells are constantly becoming old and being outcompeted and outbred by cells that stay young.  This is particularly true in yeast because cell division/mitosis is asymmetric; one cell, called the bud cell, gets mostly newly synthesized proteins, whereas older proteins stay in the other cell. Painstaking experiments in which a scientist repeatedly separated the mother and bud after each division for many generations have shown that a mother begins to show signs of aging after about 25 divisions and usually becomes senescent (stops dividing) around 40, although there are mutations that can alter these numbers (interestingly, some mutations actually extend the ‘reproductive lifespan,’ as does caloric restriction, meaning that the food source is relatively meager–this is also true in mice).  Each newly produced bud cell then becomes a first-generation mother, which will eventually become old, but not before it has produced very many brand-new bud cells itself.  

So, aging does occur in this single-celled organism, but it is not readily apparent because the population is always a mix of young and old cells; the young cells reproduce, and the old cells slowly fade away.  A key idea is that cell division can be asymmetric–the two cells resulting from the division are not both ‘newborn.’  I suspect that this will be a common thing in many species.

Other single celled organisms have more apparently symmetric divisions than S. cerevisiae, but recent results indicate that in the bacterium E. coli, there is more underlying asymmetry than meets the eye, and the ‘new cell’ is more reproductively successful than the old cell; the reference is PLoS Biol. 3, e45 (2005).  So, there is aging, but not in a way that endangers the long-term viability of the population. This is somewhat analogous to populations of multicellular organisms, including humans–parents go to a lot of trouble to produce offspring that are brand spanking new (pun intended), and of course the offspring will outlive their parents all else being equal.

Any thoughts?  Questions?  Suggestions?  I’d like for this to be somewhat interesting, so if this is too much above/below your level, feedback would be useful.  Also, I hate to sound like I’m begging for attention, but I will be much more likely to continue this if I know there are people who are reading, so just saying that you like it would be appreciated.  

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