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The researchers tested mice brains for the secret behind brain cell death.  (Source: Recognizing Deven)

The researchers found an important culprit in the cause of brain cell death -- a tumor killing preventing enzyme surpress AKT (pictured here), a critical protein to cell survival.  (Source: The Institute of Cancer Research)
Nature's kill switch seems to activate for some brain cells but not others, according to researchers

Preventing and reversing memory loss is a key field of research in the area of prolonging human life spans.  While humans are living much longer than they once did, many suffer from debilitating conditions such as Alzheimer's disease, which limit their quality of life during their later years.

Scientists at the University of Florida may have gained a significant insight into understanding what causes some brain cells to die, triggering these diseases, while others cells remain alive.  The studies, performed on mice examined two neighboring regions in the hippocampus; an anatomical region shaped something like a curved kidney bean.  The region is thought to be central to the formation of memories, and is one of the first regions affected by brain blood flow problems or Alzheimer's.

What researchers discovered was that the higher susceptibility to cell death in part of the hippocampus versus the other region was due to the enzyme PHLPP, pronounced "flip", silences the transcription of a gene that produces a critical protein to cell survival, AKT.  AKT inhibits many causes of cell death.  The inactivation in essence, amounts to the cell flipping its own kill switch.

Thomas C. Foster, Ph.D., the Evelyn F. McKnight chair for research on aging and memory at UF describes, "The question is why does one set of brain cells live and another set die when they are only millimeters apart in the same small brain structure?  We looked at an important signaling pathway that tells cells to stay alive or die, and the enzymes that regulate that pathway. Implicated in all this is a new protein that before a couple of years ago no one actually knew much about."

The conclusions were drawn by first finding AKT levels to be a key chemical difference between the living and dying cells.  From there, the cause of the AKT shortage was traced to high levels of the enzyme PHLPP1, the mouse version of PHLPP, an enzyme found in other mammals.  Ironically, the recently discovered enzyme suppresses tumors in many cases.  The compound was discovered by Alexandra Newton, Ph.D., a professor of pharmacology at the University of California, San Diego.

Professor Newton comments on the new research, stating, "Basically, PHLPP is important in controlling whether cells survive and proliferate or die.  If you want cells to survive brain disease, diabetes or heart disease, you want active AKT signaling and therefore low PHLPP. But if you want to stop cells that have the 'go' signal, like cancer cells, PHLPP can function as a brake. In this case, it appears as if there is an area in the hippocampus that is easily stressed and might undergo ischemia easily, because PHLPP is not allowing the AKT survival mechanism to work."

According to Professor Foster, the breakthrough could lead to new drugs to combat memory loss and brain damage.  He states, "Possibly, we have found a target that could be manipulated with drugs so that these brain cells can be saved from threats.  If one area of the hippocampus has a deficiency in cell-survival signaling, it is possible to find a way to ramp up the AKT protein. The caveat is, there are studies that show over-activating AKT may not be good for memory — AKT may be naturally lower in this region for an important reason. But in times of intense damage, there may be a therapeutic window to upregulate AKT and get some benefit to health."

It is still unknown why some regions of the brain flip the switch to trigger cell death, while others, which appear equally vulnerable to tumor formation, do not.

The research is published online in the Nature publication Cell Death & Differentiation.  



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I don't want to live that long
By omgwtf8888 on 12/12/2008 1:30:50 PM , Rating: 2
We had a discussion about all the scientific improvements to extend life, and even the possibility of a pill that could let you live for 400 years. Here is the problem! If you live to be 400, they can't let you retire at 65. No! You would have to work until you were 350 years old. Think about going to that cubicle for 350 years... imagine the dust? Anything you could possibly do would become so boring after hundreds of years. Forget about suicide brain cells, I think you would opt for the solient green program.. It's People!




RE: I don't want to live that long
By jkresh on 12/12/2008 3:05:39 PM , Rating: 2
You are correct that retiring at 65 if you are going to live to 400 is unlikely for most people (certainly not on a pension) but if you have enough money you could (though I suspect even billionaires would go back to work at some point).
As for working in that "cubicle for 350 years", how many jobs today existed 350 years ago (or are similar in form)? You would switch jobs and things would change as new technology came out new jobs would become available (and old ones would disappear). While I would agree that some people would have difficulty adjusting I think a significant percentage could adapt (and after a generation or to when people begin to grow up with the idea of living that long then most would adapt).

All that being said while there are some interesting things in labs that suggest at radical life extension in the near future, there are also a lot of problems that will need to be addressed first, and likely unforeseeable issues (ie diseases or aging related things that we haven't seen because people don't live long enough now that will show up when we start living past 150...)


By JonnyDough on 12/12/2008 10:44:50 PM , Rating: 3
You have to take into account a few things.

First, quality of life over a long time frame improves. You will get really good at your job. You will accumulate wealth as well. Furthermore, you will be more educated and become a better teacher to others - so that they learn to value you more, and as a society we might progress better.

People would see things in a more long-term perspective. We would stop letting politicians get away with short term fixes perhaps. We would war less maybe...etc.

Take for example, kids today who live recklessly. If you warn them about how a choice they make may affect them for the rest of their life, they don't listen because they don't care. They "don't want to live to be that old. It's gross, and life will suck."

But, if you're walking around at 300 yrs old and are happy, they'll look at you and maybe want to be there someday. The gravity of their choice may weigh in a bit more, because they'll have to consider living with that choice for a much much longer period of time. By the time they decide to do something stupid to themselves, maybe they'll be educated enough not to. I can't imagine getting smarter for 300 years and then acting like a total jackass.


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