February 09, 2012
Old Immune Cells Missing Big DNA Pieces
Impairment of aging immune cells might be at least partially explained by alterations in DNA.
In a recent study led by Uppsala University, the researchers compared the DNA of identical (monozygotic) twins of different age. They could show that structural modifications of the DNA, where large or small DNA segments change direction, are duplicated or completely lost are more common in older people. The results may in part explain why the immune system is impaired with age.
During a person's life, continuous alterations in the cells' DNA occur. The alterations can be changes to the individual building blocks of the DNA but more common are rearrangements where large DNA segments change place or direction, or are duplicated or completely lost. In the present study the scientists examined normal blood cells from identical (monozygotic) twins in different age groups and looked for large or smaller DNA rearrangements.
In white blood cells of people over the age of 60 some large chunks of chromosomes are missing. Probably not coincidentally, immune function declines with age.
The results showed that large rearrangements were only present in the group older than 60 years. The most common rearrangement was that a DNA region, for instance a part of a chromosome, had been lost in some of the blood cells. Certain, almost identical, rearrangements were found in several individuals and some of these could be correlated with a known blood disease in which the bone marrow's capacity to produce new blood cells is disturbed. Rearrangements were also found in the younger age group. The changes were smaller and less complex but the researchers could also in this case show that the number of rearrangements correlated with age.
– We were surprised to find that as many as 3.5 percent of healthy individuals older than 60 years carry such large genetic alterations. We believe that what we see today is only the tip of the iceberg and that this type of acquired genetic variation might be much more common, says Jan Dumanski, professor at the Department of Immunology, Genetics and Pathology and one of the authors of the paper.
Imagine getting your white blood cells replaced as you age with youthful cells grown up from the least damaged cells in your body. Get a youthful immune system to replace your aging cells. The benefits would be many fold. Your risk of death from pneumonia and flu would go down of course. But also, the immune system kills cancer cells and as it ages it becomes less able to do so. Therefore a rejuvenated immune system would lower your risk of cancer. It might even be possible to enhance your immune system to make immune cells far more effective against cancer.
Replacement of aging immune cells with youthful and undamaged immune cells might also slow brain aging as immune T cells probably play a role in formation of new nerve cells.
In the present study, the scientists showed that the same immune cells may also be key players in the body's maintenance of the normal healthy brain. Their findings led them to suspect that the primary role of the immune system's T cells (which recognize brain proteins) is to enable the "neurogenic" brain regions (such as the hippocampus) to form new nerve cells, thus maintaining the individual's capacity for learning and memory.
We need cell therapies that replace aging cells with much more youthful cells. The immune system seems like a great place to start because its cells already circulate routinely through the blood stream and immune cells serve a wide range of beneficial functions.
Sounds like we each need a genetic benchmarking while young, so the equipment monitoring our genetic and epigenetic states will be able to tell what has deviated and how much.
It's usually an option these days to save a sample of "cord blood" from a newborn, which can be safely stored and serve as your "bank" to make up a batch of stem cells every sixty years or so (ha!). But it's up to the parents to understand the importance of reserving this sample of newborn tissue.
Transplanted immune cells are also ideal targets for ex vivo gene therapy. Many problems that occur with aging are linked to the inability of cells to degrade certain kinds of wastes. Highly mobile immune cells capable of targeting and degrading the wastes that compromise tissue integrity (e.g. glucosepane, which impairs among other things the suppleness and resiliency of skin, the well known amyloid deposits, or oxidated forms of cholesterol that drive accumulation of atherosclerotic plaque) could take us very far down the path of rejuvenation. Ex vivo gene therapy offers increased safety, because the modified cells can be interrogated to determine that the modifications were performed correctly and site-specifically.
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That's all folks.
the decline in information makes sense...
the folding and un-folding process seems like a game of 'telephone'.
with each replication of the message, a little more is lost.
would be interested to see if there exists a variation within immune cells, within the same organism, as opposed to a twin study.
if the info that is left out is consistent across the different immune cells of the same type, the implications are a matter of design flaw.
In theory it shouldn't be necessary to bank cells for decades. You've got the person right there, in principle it ought to be feasible to determine from a gene sequencing all the information necessary to program a set of immune cells for them. Probably starting from modified immune cells with various improvements.
Immune cells don't have to be genetically matched to the person they're in, in order to do their job properly. They just have to be 'programed' to ignore anything that's supposed to be present. The human immune system goes through a programming system, where a genetic shuffling process produces a huge variety of cell lines producing different antibodies. Then those cell lines producing antibodies which react against self are killed off, before the immune system switches to it's normal, "kill what's not self" mode.
What you need to do, I think, is take some very young cells, initiate that genetic shuffling, and then expose them to all the proteins which *ought* to be found in the individual's body, to eliminate the lines which would cause auto immune disease. And then implant them in the body.
I'm not suggesting this because cord blood banking isn't a good idea, just because most of us haven't had it done...