I am starting this section as a general archive for specifically technical and scientific work involving the *PROCESS* of aging. I think that this needs to be distinguished from philosophical, sociological and even perhaps the psychological aspects. [!]
In the case of this article it crosses over into the discussion of telomers and I will link it to that topic but I think that we also need to become closely attuned to the nuances of the actual process of aging from a general perpsective and not see this as a single *key* that must be identified in order to unlock the *secret*. [hmm]
LL
http://www.nature.co.../020819-13.html
Ageing chromosomes
ELEANOR LAWRENCE
All living things age, in one way or another, and despite years of research it has proved surprisingly difficult to explain why. Why, for example, do our repair mechanisms seem to become less efficient with age, so that we lose the natural resilience of youth to minor physical injury and physical stress?
A hot topic in ageing research at present is the enzyme telomerase, an enzyme that maintains the protective "seal" on the end of each chromosome. These ends are called telomeres. They prevent the chromosomes from fusing with each other to produce abnormalities, and protect the chromosome ends from being nibbled away by enzymes in the cell. Your chromosomes are precious and have to last a lifetime. They make copies of themselves at each cell division, but this also means that any damage sustained in the interim is passed on to the new cells.
Lack of telomerase results in a progressive shortening of telomeres each time cells divide, and telomere shortening has been linked to the changes seen in cultured human cells as they "age" in their culture dishes in the laboratory. But it is not clear yet that this has anything to do with physiological ageing in humans, even though it has been shown that human body cells make very little telomerase.
One thing that has been lacking so far is a good animal model in which to study the role of telomerase in ageing. The mouse has much longer telomeres than humans and seems to produce more telomerase, so it seems unlikely that telomere shortening has have much effect over its natural lifespan. To make mice more like men, Karl Lenhard Rudolph from the Dana Farber Cancer Institute, Boston, Massachusetts and colleagues, made a strain of mutant mice that lacked the enzyme telomerase completely. Successive generations of these mice have shorter and shorter telomeres.
Rudolph and colleagues followed the progress of successive generations of these mutant mice for two-and-a-half years. In sixth generation mice, which have the shortest telomeres to start off with, some effects are apparent from a very early age. The third generation mice appear perfectly healthy when young, despite having shorter than normal telomeres. And effects are even less severe in first generation mutants. As Rudolph and colleagues report in the journal Cell [March 5] the more severely affected mutant mice show some changes reminiscent of human ageing, and these changes are more severe and are apparent earlier in the mice with the shortest telomeres.
Although none of the mice showed signs of a generalized premature ageing, the sixth generation mice had a shorter life span than normal. In the later generations of mice, the fur went gray earlier and, like ageing humans, they were less able to heal skin wounds efficiently. They regenerated blood cells from bone marrow at a slower rate than do normal mice and their cells also had a higher frequency of chromosomal abnormalities reuslting from chromosome fusion. The mice also showed a higher incidence of spontaneous cancer.
The researchers suggest a role for telomere shortening in the reduction of the regenerative capacities of tissues such as the skin and lymphoid organs that naturally have a high turnover of cells and whose cells are thus undergoing continual rounds of cell division. In these tissues, the already short telomeres will shorten still further at each round of cell division. In contrast, more 'stable' organs such as heart and blood vessels, liver, kidneys and brain, showed no ageing-related changes in structure or function in these mice. Rudolph and colleagues suggest that their mouse mutant will be a good model to study "that hallmark feature of ageing -- a reduced capacity to tolerate acute stress".
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