You might recall the recently voiced suggestion that it’s something of an accident of history that the cryonics movement is the cryonics movement versus the plastination movement. Plastination is plausibly just as good a way of preserving the fine structure of the brain into a future where a patient can be restored to life as low-temperature storage.
Twenty years ago, Charles B. Olson published an article called “A Possible Cure for Death” in the journal Medical Hypotheses. In it, he favorably compares methods of chemical preservation to cryogenic preservation. Unfortunately, this article provoked no wide discussion or attempts at implementation. As the author notes on his website, other than requests for reprints, “nothing more came of it.” And yet the arguments in it are still sound and just as persuasive today as they were then.
Not so long ago on the Cryonet list, a fellow asked: “How can we help those who cannot afford cryonics?” This is a valid question, given that the high level purpose of cryonics is to offer some alternative to oblivion for those who die before the advent of working rejuvenation medicine. While cryonics is very affordable if you plan ahead and take out a low-cost life insurance plan, there will always be those who get caught short through no fault of their own.
Here, plastination steps forward as a possible alternative that would cost little more than what is already spent on the disposal of remains. Plastinate the brain for the cost of an embalming, and cremate the rest. You’re now set for a good number of decades in any very low-cost storage facility.
The way we do it is chemical preservation with the option to convert to cryopreservation. … A hospital pathologist can remove the brain and submerge it in fixative. It would be shipped after 1 week in fixative. Permanent storage could be in fixative for the truly indigent. But a better option for those who could afford it would be to convert to cryopreservation. The cost might start at about $20,000, but could get down to about $12,000 after the first few due to economies of scale. The brain would remain in fixative until the full cryopreservation cost was paid for, and only then go into a dewar.
The economic advantages are considerable due to cutting out the need for a standby team to prepare a patient for cryopreservation - though as noted in the past, open questions remain as to how important it is to act quickly and whether and to what degree different types of preservation strategy affect the preservation of brain structures important to the mind’s data.
But all of the above discussed options are better than no plan at all, a path that leads to oblivion and the grave. This is just another of the many ways in which the world we live in is a madhouse of waste, death, and destruction compared to other plausible worlds - such as the one in which people generally chose to have their brains plastinated and stored at death for the past few decades, allowing hundreds of millions of the deceased a shot at living again in the future. But in this world, they are all dead and gone, lost forever.
Continue Reading April 21st, 2009
If you’ve been following along for the past couple of years, you’ll recall that one important part of aging is the build-up of damaging biochemicals both within and between our cells. These by-products of metabolism eventually grow to a level at which they greatly interfere with the functioning of our cells, tissues, and organs - or even kill us.
What we’d really like to see developed over the next decade or two is an outgrowth of the targeted nanotechnology, immune therapies, and viral therapies presently in the laboratory aimed at these aggregates. Given that we make it to 30 years of age without too much harm resulting, getting the build-up cleaned out every decade should prevent it from contributing to aging in any way.
Of course that’s much easier to say than accomplish, and there are many, many different forms of unwanted biochemical involved in this part of the aging process. Fortunately for us, I think that the parallel labor of listing and then figuring out how to safely break down many different biochemicals is a task well suited to the years ahead, in which biotechnology becomes very cheap, and many new hands join the workforce.
Meanwhile, a wide range of potential strategies for attacking, slowing, or preventing the build up of specific biochemicals are emerging. I noted a couple not so long ago. Here’s another recent line of work.
Survival mode that protects cells when oxygen is low also slows aging:
A cell’s protective reaction to a drop in oxygen is called the hypoxic response. Researchers at the University of Washington (UW) have found that nematode worms live longer if their genetic make-up permits their cells to turn on the hypoxic response under normal oxygen conditions.
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“The research findings suggest that the hypoxic response promotes longevity and reduces the accumulation of toxic proteins by a mechanism that is distinct from both dietary restriction and insulin-like signaling. It appears to be an alternative pathway, “Kaeberlein said. “However, we don’t know if future studies might reveal that all of these different genetic pathways converge somewhere down the line into a common mechanism for delaying the effects of age.”
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The key factor that controls the hypoxic response is called HIF. HIF is regulated by another protein called VHL-1 … animals lacking VHL-1 were resistant to the toxic proteins known to cause Alzheimer’s disease and Huntington’s diseases, and that their cells accumulated less of an age-pigment called lipofuscin. Lipofuscin is thought to be one indicator of an animal’s health during aging. According to Kaeberlein, “these observations may suggest that the hypoxic response not only increases life span, but also lengthens health span and protects against the molecular processes that lead to
Continue Reading April 21st, 2009
A safe technology platform to allow destruction and recreation of our immune systems would offer a lot of promise for addressing issues that arise in the aging immune system.
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.
Trials are taking place in which specific diseases of the immune system are addressed by destruction and recreation - but it’s not at present a procedure you’d enjoy all that much, having more in common with chemotherapy than medicine of the future. But hopefully we all recall that safe, painless elimination of specific cell types through nanotechnology targeting systems is on the way, and fairly advanced in the laboratory. That will make rebooting an immune system a much more practical prospect.
In any case, here is an update on one of the trials of immune system rebooting in recent years, in which the autoimmune disease of type 1 diabetes was effectively cured:
Patients who underwent a procedure to wipe out the immune system and reconstitute it with their own stem cells remained insulin injection-free for up to three to four years after the procedure … The report extends research published in 2007 showing that the majority of 15 patients who underwent a blood stem-cell transplant were able to remain insulin-free for more than 18 months.
One component of aging is that we all suffer from increasingly deranged, broken, and misconfigured immune systems. On the one hand your immune system become hyper-sensitive and creates constant low-grade inflammation that causes all sorts of issues, and on the other hand it becomes ineffective at its primary functions - fighting pathogens, killing senscent cells, and eliminating cancer cells. It’s on all the time, burning resources and causing damage, but not doing you any good.
I look forward to the years ahead in which we can have an old immune system cleared out and reset in an efficient and safe manner, using targeted cell killers and stem cell therapies.
Continue Reading April 21st, 2009
The latest Hourglass blog carnival on the biology of aging and longevity science is over at psique, and closes with an interesting historical quote:
~These bodies which now we wear belong to the lower animals; our minds have already outgrown them; already we look upon them with contempt. A time will come when Science will transform them by means which we cannot conjecture, and which, even if explained to us, we could not now understand, just as the savage cannot understand electricity, magnetism, steam. Disease will be extirpated; the causes of decay will be removed; immortality will be invented~. -Winwood Reade, 1872, from his book The Martyrdom of Man
The difference between Reade’s era and ours is that we have a fairly clear vision as to the means by which we will change our bodies for the better. We will develop biotechnological tools to repair the damage of aging that has been identified in past decades:
Many things go wrong with aging bodies, but only a few of them are primary changes in the structure of the body itself - that is, aging damage. Other changes (such as increases in inflammation and oxidative stress) are the secondary consequences of this primary change: either the direct results of those damaged components’ inability to carry out their normal role in metabolism, or the body’s adaptive or maladaptive attempts to compensate for those changes. Thus, by removing, repairing, replacing, or rendering harmless the damage, we restore the normal functioning of the body’s cells and essential biomolecules, and the secondary changes are given the chance to return to their normal, youthful baseline.
Scientists have spent decades looking for such changes in aging bodies, this research has led to the conclusion that there are no more than seven major classes of such cellular and molecular damage … We can be confident that this list is complete, first and foremost because of fact that scientists have not discovered any new kinds of aging damage in nearly a generation, despite the facts that research into aging has been slowly accelerating and that we have had ever-increasingly powerful tools with which to investigate the aging body.
If you look at the Strategies for Engineered Negligible Senescence (SENS) you’ll see that present knowledge is detailed enough for researchers to get to work, assuming they can raise the funding. Indeed, a small amount of this work has been taking place in past years, and is bearing fruit - the chief obstacles to progress here are entirely a matter of will and resources, not knowledge. When a large number of people decide to support longevity science, the field will start to look a lot like the last decade of stem cell research. Until then, progress is painfully slow considering the costs of delay.
Continue Reading April 21st, 2009
You might recall that the gene CLK-1 can influence longevity in a range of species:
CLK-1 - or clock-1 - is a gene that affects lifespan, most likely through its influence on mitochondrial activity. It’s the standard story, or at least appears to be: anything that can lower the rate at which mitochondria damage themselves will extend life in flies, mice, and so forth.
Here’s more on CLK-1 in yeast and worms; an open access PLoS Genetics paper:
Mitochondrial respiration generates energy in the form of adenosine triphospate (ATP), a molecule that powers many cellular processes. When respiration is inhibited in C. elegans, rates of behavior and growth are slowed and, interestingly, lifespan is extended.
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We find that inhibiting respiration increases the expression of genes predicted to protect and metabolically remodel the animal. This pattern of gene expression is reminiscent of the expression profile of long-lived respiration-defective yeast, suggesting ancient evolutionary conservation. Mutations in clk-1, which inhibit the synthesis of the respiratory-chain factor ubiquinone, produce gene expression, longevity, and behavioral phenotypes similar to those produced by inhibiting components of the respiratory chain.
We find that knocking down the activities of two similar genes - fsrt-1 and fstr-2- accelerates the behaviors and aging rates of clk-1 mutants … Thus, fstr-1/2, which encode potential signaling proteins, appear to be part of a mechanism that actively slows rates of growth, behavior, and aging in response to altered ubiquinone synthesis. Unexpectedly, fsrt-1/2 are not required for the longevity and behavioral phenotypes produced by inhibiting the gene isp-1, which encodes a different component of the respiratory chain. Our findings suggest that different types of mitochondrial perturbations activate distinct pathways that converge on similar downstream processes to slow behavioral rates and extend lifespan.
Our mitochondria appear to be the crux of a great many evolved mechanisms of longevity, which continues to point them out as a good place place to start when trying to prevent or reverse the damage of aging.
Continue Reading April 21st, 2009
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