At the end of last year, during the very successful Methuselah Foundation donation drive, I said:

The Longevity Meme Folding@Home team has been steadily rising through the ranks since its inception, thanks to the volunteer efforts of the many team members. The team is closing in on rank 200, a point that has been marked as a milestone for while. The lower ranks are a tough slog, but the team has been doing well - growing and producing results.

I have decided that the best thing to do to mark the passage of rank 200, rather than send out another round of Longevity Meme tchotchkes, is to donate a chunk of change to the Methuselah Foundation, where it can be put to good use in advancing longevity science. Here is my incentive for the team: pass rank 200, and stay beneath that level for a week, and I'll donate $1000 in support of Strategies for Engineered Negligible Senescence (SENS) research carried out by the Foundation.

The team recently steamed past rank 200 and, judging by the stats for surrounding teams, sub-200 ranks are here to stay. Please do drop by the Immortality Institute discussion thread for the Longevity Meme Folding@Home team to congratulate the volunteers. Congratulations all round, in fact!

I'll shortly be writing that check to fund a little more of the Methuselah Foundation's longevity science - and I hope that some of you folk decide to do the same this year. Don't forget that donations to SENS research are presently tripled by matching funds from Ryan Scott and Peter Thiel; my $1000 check will send $3000 to the researchers working on the LysoSENS and MitoSENS projects.

You might want to take a look at last month's update from the Foundation on the money rolling in and the new longevity research rolling out - things are moving along very nicely, and we hope to see even more progress in 2008.

There are many reasons why you, in some future year, may want to destroy your immune system and replace it with a new one. It's not an unreasonable goal, given that medical researchers are already doing just that in clinical trials aimed at curing automimmune conditions. The reason I have in mind - exhaustion of immunological space and effectiveness due to a lifetime of cytomegalovirus exposure - occurs to all of us, is a contributor to the degenerations of aging, and is outlined in detail back in the Fight Aging! archives.

One main reason your immune system fails with age appears to be that chronic infections by the likes of cytomegalovirus (CMV) cause too many of your immune cells to be - uselessly - specialized. ... researchers are looking into a possible way of clearing these infections from the body.

The flip side of clearing out CMV is to reboot your immune system. Clean it out and start afresh, absent the clutter of memory cells devoted uselessly to CMV that were crowding out the naive T cells needed to respond to new threats. There's more to the aging of the immune system than just this process of crowding, but it's a good start.

Here's an example of some of the foundational work that could lead to safe reconstruction of an age-damaged immune system:

A new study demonstrates for the first time that embryonic stem cells [ESCs] can be used to create functional immune system blood cells

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In this study, a team of scientists from Iowa, Taiwan, and Germany used HOXB4-containing ESCs to engraft the bone marrow and rescue mice that genetically lacked any immune system and had been irradiated to destroy their bone marrow. Only cells containing HOXB4 were able to engraft, rescue the mice, and produce blood cells long term. These engrafted cells were shown to be derived from the transplanted ESC-derived cells.

To determine if these transplants were able to rebuild the defunct immune system, the scientists injected the mice with LCMV, a common rodent virus, and watched for T-cell activity, a sign that the body was defending itself against the infection. Although the number of T cells generated by the new hematopoietic cells was low, they were able to respond effectively to the virus. In addition, the transplanted hematopoietic cells were also able to produce B cells and other defensive cells called antigen-presenting cells, which have a role in signaling T cells to action. They also tested the ability of the mice to respond to vaccination and demonstrated the induction of specific immune cells. Although the level of immune response was not what is seen in normal adult mice after exposure to the virus or vaccine, it was measurable and effective.

A way to go yet, but that's progress.

A comment on yesterday's post on advances in stem cell infrastructure technologies:

Great news, but I have this question: what possible reason or mechanism exists for assuming that an "induced" stem cell created from an already aged cell wouldn't get some of the induced damage carried along with the machinery? I can't see how this would be a 100% "reset".

Still, I imagine even a slightly pre-aged replacement organ from your own cells would be a helluva a lot better than a foreign transplant with rejection problems.

Here's another one - if you're replacing an organ or tissue because of genetic disease, how long before the newly constructed replacement would start to fail in the same way?

Which is true; a new organ grown from your own tissue is not an automatic benefit under all circumstances. However, I see the building of new organs from small numbers of stem cells as just one component of what can potentially be achieved when you can create new pluripotent stem cells to order. There is a point early in the process at which you are working with just a handful of cells, freshly extracted. There, the opportunity exists to economically apply any form of new technology aimed at manipulating, repairing or changing those cells prior to growing new tissue.

For example, lengthening telomeres, or correcting simple genetic errors. These are things that can be done today in a limited fashion - we don't fully understand the consequences, and our knowledge is small in the grand scheme of things. That won't always be the case, however, and this point of opportunity in the growth of new tissue tailored for the individual will remain as we find new and better ways to take advantage of it.

The damage of aging in our cells is "just" a wrong arrangement of molecules, when it comes down to it. It seems plausible that selecting the least damaged cells, or repairing specific forms of damage - such as replacing age-damaged mitochondria with freshly repaired versions - is a near-future approach to minimizing the damage of aging in induced pluripotent stem cells.

One caveat: it looks likely that the behavior of stem cells, or any new tissue, in the body has a great deal to do with the holistic functioning of signaling networks and the cellular environment. You can't just take the cells in isolation when thinking through potential technologies and applications - you have to consider the aged environment of the surrounding tissue.

In general, there is a great deal of good that could be achieved with the technology to create pluripotent cells from any cell - and many other lines of research that can be applied atop this foundation with the goal of building better, less damaged tissue from aged cells. Beyond that, who knows? At some point we'll be skipping the extraction of cells and just building them outright from raw materials - and around about there aging becomes somewhat moot, given the biotechnoloy that implies.

The research community is steaming ahead with a promising methodology for producing the building blocks of all tissue types directly from your own cells:

researchers used genetic alteration to turn back the clock on human skin cells and create cells that are nearly identical to human embryonic stem cells, which have the ability to become every cell type found in the human body. Four regulator genes were used to create the cells, called induced pluripotent stem cells or iPS cells.

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Reprogramming adult stem cells into embryonic stem cells could generate a potentially limitless source of immune-compatible cells for tissue engineering and transplantation medicine. A patient’s skin cells, for example, could be reprogrammed into embryonic stem cells. Those embryonic stem cells could then be prodded into becoming various cells types - beta islet cells to treat diabetes, hematopoetic cells to create a new blood supply for a leukemia patient, motor neuron cells to treat Parkinson’s disease.

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Our reprogrammed human skin cells were virtually indistinguishable from human embryonic stem cells. Our findings are an important step towards manipulating differentiated human cells to generate an unlimited supply of patient specific pluripotent stem cells. We are very excited about the potential implications.

Infrastructure is important: any advance that lowers the cost of a common tool or resource will speed progress. The new news in this latest press is that the procedure has been reproduced fairly rapidly by different research groups. It is therefore probably viable as a technology base for regenerative medicine, organ regrowth, drug testing, research into the biomechanisms of disease, and everything else you'd want a cheap supply of pluripotent stem cells to achieve.

The promise - the hoped for possibility - of cancer stem cells is that they represent a small, manageable, less complex range of biochemical targets to prevent and destroy cancer. The biotechnology of this year and next can flip genetic switches and safely destroy cells with specific markers - if we just know where to look, what to destroy, what to change.

The promise of cancer stem cells is that cancer has a simple, easily severed root. This may or may not be the case, but you can be sure that this path will be well explored over the next decade. Here is an example of the sort of result that makes cancer researchers excited:

Discovery of good -- and bad -- liver stem cells raises possibility of new treatment

Many scientists believe up to 40 percent of liver cancer is caused by stem cells gone wild - master cells in the organ that have lost all growth control. But, despite years spent looking, no one has ever found these liver "cancer stem cells" - or even normal stem cells in the organ. Until now.

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"After locating the cancer stem cells that help control development of these tumors, we were able to find a potential vulnerability that might form the basis of a new treatment for this disease - which is greatly needed," said the study’s lead author

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"We found that all of these [cancer] stem cells had lost TGF-beta,” she said. “Without the brakes that TGF-beta puts on cancer, the stem cells had turned into bad guys.”

The scientists turned to mouse models of liver cancer to see what would happen if they took out the "stemness" in the cancer stem cells and found that only 1 in 40 mice bred without a stat3 gene developed liver cancer. "But with the stat3 gene intact, 70 percent of mice developed the cancer."

Off switches for various different types of cancer - that prospect keeps researchers working hard to uncover, detail and understand more of our biochemistry.