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A toolkit for producing true rejuvenation in humans will require a range of different therapies, each of which can repair or reverse one of the varied root caus

A toolkit for producing true rejuvenation in humans will require a range of different therapies, each of which can repair or reverse one of the varied root causes of degenerative aging. Research is underway for all of these classes of therapy, but very slowly and with very little funding in some cases. The funding situation spans the gamut from that of the stem cell research community, where researchers are afloat in money and interest, to the search for ways to break down advanced glycation endproducts (AGEs), which is a funding desert by comparison, little known or appreciated outside the small scientific community that works in that field. While bearing in mind that progress in projects with little funding is unpredictable in comparison to that of well-funded projects, I think that we can still take a stab at a likely order of arrival for various important therapies needed to reverse aging. Thus an incomplete list follows, running from the earliest to the latest arrival, with the caveat that it is based on the present funding and publicity situation. If any one of the weakly funded and unappreciated lines of research suddenly became popular and awash with resources, it would probably move up in the ordering: 1) Destruction of Senescent Cells Destroying specific cells without harming surrounding cells is a well-funded line of research thanks to the cancer community, and the technology platforms under development can be adapted to target any type of cell once it is understood how to target its distinctive features. The research community has already demonstrated benefits from senescent cell destruction, and there are research groups working on this problem from a number of angles. A method of targeting senescent cells for destruction was recently published, and we can expect to see more diverse attempts at this in the next few years. As soon as one of these can be shown to produce benefits in mice that are similar to the early demonstrations, then senescent cell clearance becomes a going concern: something to be lifted from the deadlocked US regulatory process and hopefully developed quickly into a therapy in Asia, accessed via medical tourism. 2) Selective Pruning and Support of the Immune System One of the reasons for immune system decline is crowding out of useful immune cells by memory immune cells that serve little useful purpose. Here, targeted cell destruction can also produce benefits, and early technology demonstrations support this view. Again, the vital component is the array of mechanisms needed to target the various forms of immune cell that must be pruned. I expect the same rising tide of technology and knowledge that enables senescent cell targeting will lead to the arrival of immune cell targeting on much the same schedule. Culling the immune system will likely have to be supported with some form of repopulation of cells. It is already possible to repopulate a patient's immune system with immune cells cultivated from their own tissues, as demonstrated by the limited number of full immune system reboots carried out to cure autoimmune disorders. Alternatives to this process include some form of tissue engineering to recreate the dynamic, youthful thymus as a source of immune cells - or more adventurous processes such as cultivating thymic cells in a patient's lymph nodes. 3) Mitochondrial Repair Our mitochondria sabotage us. There's a flaw in their structure and operation that causes a small but steadily increasing fraction of our cells to descend into a malfunctioning state that is destructive to bodily tissues and systems. There are any number of proposed methods for dealing with this component of the aging process - either repairing or making it irrelevant - and a couple are in that precarious state of being just a little more solidity and work away from the point at which they could begin clinical development. The diversity of potential approaches in increasing too. Practical methods are now showing up for ways to put new mitochondria into cells, or target arbitrary therapies to the interior or mitochondria. It all looks very promising. Further, the study of mitochondria is very broad and energetic, and has a strong presence in many areas of medicine and life science research. While few groups in the field are currently engaged in work on mitochondrial repair, there is an enormous reservoir of potential funding and workers awaiting any method of repair shown to produce solid results.

mrfusion 11y ago
Thanks for the detailed write-up. Very interesting reading! I don't understand what you're saying about pruning the immune system. What is that trying to fix? What goes wrong with the immune system as it ages?
- reasonattlm 11y ago
  The immune system operates more or less as a limited capacity system. It has low levels of replacement of immune cells in old age. For reasons that may have to do with exposure to persistent herpesviruses there is an expansion of memory cells and related types at the expense of the naive T cells needed to deal with new threats. So the quick and dirty solution to this, which has some support from animal studies in the past few years, is to selectively kill off the undesirable excess memory cells. Perhaps via one of the targeted cell killing technologies developed in the cancer research community. This should free up capacity and spur the generation of more naive T cells to replace the lost numbers. It isn't a reality yet, but all the pieces are more or less in place. Someone just needs to do it. A similar thing was demonstrated for B cell destruction in mice (innate immunity, not adaptive immunity): the bad cells were stripped out, and fresh new cells were generated as a result, and the innate immune response improved.
mrfusion 11y ago
Do you see a place for regrowing organs in your list, or do these other methods make that unnecessary? What about stem cell injections?
- reasonattlm 11y ago
  Regeneration and regrowth should be in situ where possible. Stem cell treatments are clearly beneficial, but will most likely give way to other methods of directly altering the behavior of native cells. Delivering signal molecules into the environment, or small molecules capable of otherwise adjusting cell epigenetic state. In the final analysis if you can repair other forms of damage, many of the issues with regeneration should go away, as lost healing capacity is a result of age-related stem cell decline that it is in turn largely a reaction to a damaged environment. This of course needs to be proved. The best way to prove it is to implement the damage repair biotechnologies, see what happens. Currently the major research focus in the mainstream is not to repair damage at all. It is rather to identify changes in signals and reverse them, and thus wake up stem cells and put them back to work on tissue maintenance, even damaged as they are and damaged as the tissue environment is. This is actually producing far better results with far less cancer as a result than you might think it would, which is always a bonus, but it isn't what I would consider the best path ahead. Replacement of stem cell populations in the old are probably a necessary treatment. Clear out all damaged cells and generate a set of replacement cells from the patient's own tissues. Do that and then the organs should sort themselves out, except for gross damage that might need more treatment to rescue, such as deformation of the cardiovascular system as a result of hypertension that probably won't reverse itself.

mrfusion 11y ago

Thanks for the detailed write-up. Very interesting reading! I don't understand what you're saying about pruning the immune system. What is that trying to fix? What goes wrong with the immune system as it ages?

reasonattlm 11y ago
The immune system operates more or less as a limited capacity system. It has low levels of replacement of immune cells in old age. For reasons that may have to do with exposure to persistent herpesviruses there is an expansion of memory cells and related types at the expense of the naive T cells needed to deal with new threats. So the quick and dirty solution to this, which has some support from animal studies in the past few years, is to selectively kill off the undesirable excess memory cells. Perhaps via one of the targeted cell killing technologies developed in the cancer research community. This should free up capacity and spur the generation of more naive T cells to replace the lost numbers. It isn't a reality yet, but all the pieces are more or less in place. Someone just needs to do it. A similar thing was demonstrated for B cell destruction in mice (innate immunity, not adaptive immunity): the bad cells were stripped out, and fresh new cells were generated as a result, and the innate immune response improved.

mrfusion 11y ago

Do you see a place for regrowing organs in your list, or do these other methods make that unnecessary? What about stem cell injections?

reasonattlm 11y ago
Regeneration and regrowth should be in situ where possible. Stem cell treatments are clearly beneficial, but will most likely give way to other methods of directly altering the behavior of native cells. Delivering signal molecules into the environment, or small molecules capable of otherwise adjusting cell epigenetic state. In the final analysis if you can repair other forms of damage, many of the issues with regeneration should go away, as lost healing capacity is a result of age-related stem cell decline that it is in turn largely a reaction to a damaged environment. This of course needs to be proved. The best way to prove it is to implement the damage repair biotechnologies, see what happens. Currently the major research focus in the mainstream is not to repair damage at all. It is rather to identify changes in signals and reverse them, and thus wake up stem cells and put them back to work on tissue maintenance, even damaged as they are and damaged as the tissue environment is. This is actually producing far better results with far less cancer as a result than you might think it would, which is always a bonus, but it isn't what I would consider the best path ahead. Replacement of stem cell populations in the old are probably a necessary treatment. Clear out all damaged cells and generate a set of replacement cells from the patient's own tissues. Do that and then the organs should sort themselves out, except for gross damage that might need more treatment to rescue, such as deformation of the cardiovascular system as a result of hypertension that probably won't reverse itself.