Re: What causes cells not to reproduce perfectly?

This is a very interesting question and gets right at the heart of the why we age and how can we slow down that aging process. The first part of your question addresses the reason for a decrease in the perfection of cellular reproduction. DNA replication has a very impressive accuracy rate. This accuracy is achieved by a complex of proteins that forms a replication machine. This machine selects the correct nucleotide by means of base-pairing with the template strand, it then links the new nucleotide to the end of the growing chain by forming a covalent bond and also provides a correction mechanism that eliminates imperfectly positioned nucleotides. The error rate is estimated at less than one mistake for every billion nucleotides. The replication machinery does make mistakes however. It may add a few bases or put a T where a C should have been. Any change will constitute a genetic error and is called a mutation. This mistake will be copied in all future generations and may have important consequences for the cell depending on where the mutation occurred. A mutation may lead to inactivation of an important protein and cause degenerative changes in a cell or cell death or may be a "silent" mutation and have no apparent negative effects.

The next part of your question addressed whether or not cells know how many times they have reporduced. One theory of cellular senescence is called the Hayflick Theory. This theory (on a basic level) states that chromosomes contain sequences at their ends called telomeres that are progressively shortened with each cell division. Several other theories have been proposed to explain ageing including the genetic theories, the damaging action of free radicals, immune deficiency, etc. For example, the actions of free radicals may lead to the inactivation of key proteins within a cell-making the cell less capable of accurate DNA replication or slower to repair other cellular damage. All of these theories share several points in common: their genetic determinism or repercussions which appear to be part of the heritage of complex organisms. Progress in genetics with chromosome decoding to localise genes and genetic manipulations or control of gene expression will probably allow an increased life expectancy, perhaps in the near future. Currently, the human genome project, which is sequencing all of the human genome, will be completed early in the next century (5-6 years from now). This will hopefully provide us with information on news genes that may control the aging process. Currently, studies on genes that control aging focus on aging accelerated disease like Progeria. There is a disease called Werner's syndrome that is intensely studied. Recently, a gene was identified that leads to this disease. The next decades will no doubt yield much information in this area.

Lastly, you inquired about the regeneration of different types of cells in our bodies. It is true that the brain cell called a neuron does not divide. Other brain cells termed glial cells do divide. There are so many different types of cells in our bodies and they are dividing at different rates and under different genetic control that you can easily see the difficulty in finding one common mechanism that controls aging in these cells.

Marni Harris-White, Ph.D