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Negative Feedback Causing Aging?


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#1 maestro949

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Posted 21 June 2006 - 01:43 AM


This is interesting. These two mice were parabiolically joined. Instead of the older mouses immune system improving, the younger mouse actually went downhill! WTH? Does this suggest that there is something in the blood of the aged mouse that caused the young mouse to age faster? i.e. some type of negative feedback?




SCIENCE REPORTS --- by THOMAS K. DONALDSON, PhD.

Parabiosis, aging, and the immune system.

One important method to investigate the changes which take place with aging is to study mice which have been surgically joined together so that their blood and lymph circulates through both animals. The name of such a procedure is "parabiosis." Of course, if the animals so joined are sufficiently different genetically (which is exactly what would usually happen), their combined immune systems will simultaneously reject one another and both animals will die. The usual scientific experiments with parabiosis, however, get around this problem by using mice known to coincide on all the immune factors.

The advantage of parabiosis in the study of aging is that it allows us to distinguish experimentally between changes in hormones of aging animals and changes in their cells not caused by hormones. For the hormones and/or other factors circulating in the blood of parabiotic mice will be identically. Some scientists have already used this technique to study aging. (Ludwig, FC; Elashoff, RM; "TRANS NY ACAD SCI" 134: 1972. 582-7).

A much more recent and quite interesting study has just appeared in which parabiosis was used to attempt to discover reasons for the decline of the immune system in aging mice. G.M. Butzenko and I.B. Gubrii, of the Institute of Gerontology in Kiev, USSR, report in "EXPERIMENTAL GERONTOLOGY" (15: 1980. 605-10) on a very thorough study of the immune system in parabiotic mice. Two mice of different ages, one 3 months old and the other 22 months old, were parabiotically joined. The immune system of the old animals was little improved by that of the young animal joined to it. On the other hand, the immune response of the young animal markedly deteriorated, and in the same way it occurs in the old. Butzenko and Gubrii tried several modifications of their experiment. Some researchers had found that removing the spleen of old animals will increase their lifespans (Makinodan et al, "J AM GERIATRIC SOC" 24: 1976. 249), so Butzenko and Gubrii studied another set of parabiotic animals in which the older animals had had their spleens removed at the time of joining. Unfortunately, this did not improve the immune system of the partners.

Again, the authors tried irradiating the old animals to neutralize their immune system. They report that this operation DID increase the immune response of the pair. Butzenko and Gubrii feel that their results are good evidence that in the old animals there is some feedback process which is inhibiting their immune system, and that when an old animal is parabiotically joined to a young one, this same process works to inhibit the immune systems of both.

They point out an interesting speculation: that with aging, some inhibitory factors normally controlling growth in the young may continue their production and cause deterioration in the old.

Link

Edited by maestro949, 31 July 2007 - 10:31 PM.


#2 maestro949

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Posted 21 June 2006 - 01:49 AM

Oh, and to eliminate the difference in immune system why not let a mouse age and then clone him and then glue Mouse and MiniMouse together.

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#3 maestro949

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Posted 21 June 2006 - 01:53 AM

But then this seems to contradict the above...

Young Blood Makes Muscles Spry

as does this...

FIGURE 1. Heterochronic parabiosis restores muscle regeneration and muscle stem cell activation in aged animals.

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#4 maestro949

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Posted 21 June 2006 - 02:14 AM

Here we go. This sums it up nicely.

Rejuvenation of aged progenitor cells by exposure to a young systemic environment

It boils down to the fact that aged cells have a Notch pathway switched off that prevent stem cells from regenerating the tissue. Bottom line. Fix this Notch pathway, stems cells start doing their job again thus reverse the aging affect.

It still doesn't explain why old tissue causes young tissue to flip to thinking it's aged...

We hypothesized that there are systemic factors that support the robust regeneration of tissues in young animals and/or inhibit regeneration in old animals, and that these factors act to modulate the key molecular pathways that control the regenerative properties of progenitor cells.

That's quite profound and needs to be understood better! Perhaps this is why mice age so rapidly? These "systematic factors" inhibit regeneration much earlier in the lifespan of a mouse.

#5 maestro949

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Posted 21 June 2006 - 02:27 AM

There's already a patent on this. Wow.

Patent

#6 maestro949

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Posted 21 June 2006 - 02:29 AM

And a movie

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#7 John Schloendorn

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Posted 21 June 2006 - 02:35 AM

But then this seems to contradict the above...

The 2005 paper focused on the (small) beneficial effect on the old mouse -- later they learned more about the (large) detrimental effect on the young mouse.

Oh, and to eliminate the difference in immune system why not let a mouse age and then clone him and then glue Mouse and MiniMouse together

Lab strains of mice are as good as clones through inbreeding anyway. (Otherwise parabiosis would be impossible due to rejection)

Check out Irina's SENS2 talk on TGF-b and other stuff in aged mouse blood. (but she might have cut some of the good stuff out of the online version...)

Perhaps this is why mice age so rapidly?

As you can learn from the patent, the major systemic factor is now known as TGF-b. We have that too, and it increases with age quite similarly to what is seen in mice.

Stay on the lookout for upcoming papers by the same authors -- I have a feeling it's gonna rock ;-)

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#8

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Posted 21 June 2006 - 04:00 AM

Nice research Maestro. Cheers.




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