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Scientific Reviews On Aging


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#1 Lazarus Long

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Posted 26 August 2002 - 03:41 PM


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".

© Macmillan Magazines Ltd 1999 - NATURE NEWS SERVICE

#2 Lazarus Long

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Posted 26 August 2002 - 03:50 PM

http://www.nature.co...7/990527-1.html

The living end

SARA ABDULLA

Dolly, the most famous sheep in the world, is in the limelight again: this time because of her chromosomes. According to a report in the 27 May issue of Nature from Paul Shiels of PPL Therapeutics in Roslin, Midlothian, UK and colleagues, Dolly, and two other sheep cloned in slightly different ways seem to have shorter telomeres than normal sheep of the same age. Telomeres are the end-sequences of chromosomes that are believed to wear down with age. But does this mean that Dolly and other cloned sheep will age more quickly than sheep created the old-fashioned way? The answer, as is often the case in science, is 'yes' and 'no'.

Some researchers believe that telomere length is related to an organism’s age because of the DNA erosion that occurs at the ends of chromosomes when a cell makes two copies of its genetic material in order to divide. The older an organism, the more times its cells will have divided, and the shorter the telomeres on the ends of its chromosomes. An animal like Dolly would have started life with telomeres as short as those of the adult tissue whence she was cloned.

Indeed Shiels' group, which includes members of the original Roslin Institute team who carried out the now-legendary cloning experiment, found that Dolly, who was cloned from an adult sheep, seemed to have the shortest telomeres, followed, by animals ‘6LL6’ and ‘6LL7’, which are clones from embryonic rather than adult tissue. Veterinary examinations confirmed that all three animals seem otherwise normal.

Interestingly, 6LL7, whose ‘progenitor cells’ (the cells which contributed her DNA) were the youngest, had telomeres most akin to those of its non-cloned peers.

This research is just one aspect of the current research interest in the relationship between telomeres, cellular life span and hence whole-organism ageing. Geron Corporation of Menlo Park, California -- the company that recently bought Roslin Bio-Med, the biotechnology business arm of the Roslin Institute -- has found some evidence that telomeres may act like cellular fuses. Telomeres could protect chromosomes from the ravages of time until eventually after many, many divisions they are worn away completely, prompting the cell to commit suicide.

In reality, the relationship between ageing and telomeres is far more complex than this description suggests. It is known that mice and yeast deficient in the enzyme telomerase -- which maintains the length of telomeres -- can survive many generations without showing any ill effects. This indicates that either telomere length does not contribute to ageing or that an alternative telomere-maintenance mechanism takes over in the absence of telomerase. Moreover, the entire basis of the theory was recently called into question with the announcement, in Cell (14 May 1999) that telomeres were looped at the ends, so could not be simply worn down in the way people had imagined.


© Macmillan Magazines Ltd 1999 - NATURE NEWS SERVICE

#3 caliban

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Posted 27 August 2002 - 03:09 AM

aaah well.
I still don't see this to be the learning channel, but why not. [roll]

This is a review (one of dozens!) on the subject.

You will notice that it is also an opinion -> am I asking to much if I hope for a comment from some of you?


---
Rejuvenating views of the ageing process
Stephen L. Helfand and Sharon K. Inouye
NATURE REVIEWS | GENETICS
VOLUME 3 | FEBRUARY 2002 | 149-153

Attached Files



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#4 caliban

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Posted 03 September 2002 - 08:52 PM

Hm. 3 downloads until now! I can see you are either not very interessted in aging theory or already very familiar with it.


Hmm.





Ah what the heck, here goes another one:

This one is more dear to me as I had quite a hand in writing it. B)
Although, being a non-scientist, my name does not appear in the title. [cry]
Well its probably just as well, as it was a rather rushed and crappy job. [blush]
Still, make sure you cite this one properly and abundantly! :D
Well those three people who will actually download it... ;))

K. Merker, A. Stolzing, T. Grune
Proteolysis, caloric restriction and aging
Mechanisms of Ageing and Development
122 (2001) 595–615


PS: If I continue doing smilies at this rate I will consider changing my nick to "caliban Long"

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  • Attached File  9.pdf   225.14KB   90 downloads


#5 Lazarus Long

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Posted 03 September 2002 - 10:51 PM

Quite the opposite, I found the links very rewarding but I haven't had the opportunity to respond directly. Because all the data was in different windows for PDF 's and opening too many programs has been crashing my machine plus here it has been hectic with the start of school for my children. But this is part of the reason I think it is just better to post the article here and then quote or comment directly below in the reply window. I did thank you for them in a PM however.

Anyway I thought the first three articles were great but I haven't yet fully digested them. Yes I am familiar with a lot of the info but I think the third article was very comprehensive and informative as to focusing the salient issues.

Keep 'em coming which ever way you choose.

#6 Bruce Klein

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Posted 04 September 2002 - 05:28 PM

Caliban,

If you get a chance could you re-upload that second PDF.. I wasn't able to download it.

As to your first PDF... "Rejuvenating views of the ageing process", great article.. I found some good info there that'll come in handy for the next Part of the FAQ. Such as the example of no loss of function with age in certain species of turtles.

#7 caliban

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Posted 04 September 2002 - 10:56 PM

Hey Lazarus Long and BJKlein: my whining was certainly not directed at you!
I certainly suspected that out of the 3 hits 2 could be attributed to you.

QUOTE
If you get a chance could you re-upload that second PDF.. I wasn't able to download it.


Hm? Works fine for me... just takes some time to open.

But here it goes again:

If this still does not work, I could post the original article, but with other articles I would rather not do that, partially because of copyright issues discussed elsewhere, partially because of differing perception of purpose discussed elsewhere, partially because of aesthetic reasons (copypasting messes up the formatting) and mainly because your average article has about 20+ pages -that's a bit much for a forum I think.




K. Merker, A. Stolzing, T. Grune
Proteolysis, caloric restriction and aging
Mechanisms of Ageing and Development
122 (2001) 595–615

Attached Files






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