Tag Archives: repair

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MILE / U.S. Transhumanist Party Interview with Ira Pastor of Bioquark, Inc.

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The New Renaissance Hat

G. Stolyarov II

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Gennady Stolyarov II, Chairman of the U.S. Transhumanist Party, was honored to interview entrepreneur and pharmaceutical industry veteran Ira Pastor for MILE – the Movement for Indefinite Life Extension – the U.S. Transhumanist Party, and the Nevada Transhumanist Party. The hour-long conversation delved into a variety of interrelated subject areas, including regeneration and repair mechanisms in animals, potential applications in humans, development of substances and treatments that could achieve victories against diseases and lead to longer lifespans, political and regulatory implications for the development of such substances, the importance of awareness of this research within the broader society, and even a “moonshot” project called ReAnima for repairing traumatic injury to organs and tissues that would otherwise cause irreversible death in accident victims.

This interview took place on Saturday, February 11, 2017, at 10 a.m. U.S. Pacific Time.

Read about Bioquark here.

Read about Mr. Pastor here.

Join the U.S. Transhumanist Party for free here.

Visit and like the MILE – Movement for Indefinite Life Extension – Facebook page here.

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Updates on a Crowdfunded Mouse Lifespan Study – Article by Reason

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The New Renaissance Hat
Reason
January 3, 2015
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For all that I think it isn’t an efficient path forward, one likely to produce meaningful results in moving the needle on human life spans, there is considerable interest in testing combinations of existing drugs and various dietary compounds in mice to see if healthy life is extended. I expect that as public interest grows in the prospects for aging research to move from being an investigative to an interventional field, wherein researchers are actively trying to treat aging, we’ll only see more of this. There is certainly a sizable portion of the research community who think that the the best path ahead is in fact the pharmaceutical path of drug discovery in search of ways to slightly slow the aging process. To their eyes slightly slowing the aging process is all that is plausible, and adding five healthy years to life by 2035 would be a grand success. Google’s Calico initiative looks set to take that path, for example, which I is why I’m not all that hopeful it will produce meaningful results in terms of healthy years gained and ways to help the old suffer less.

There is a considerable overlap between researchers aiming to gently slow aging via drug discovery and researchers whose primary motivation is still investigation, not intervention: to produce a complete catalog of metabolism and how it changes with age, and it’s someone else’s problem to actually use that data. So we have, for example, the Interventions Testing Program at the NIA. This program was long fought for by researchers tired of the lack of rigor in most mouse life span studies, and the people involved are essentially engaged in replacing a lot of carelessly optimistic past results with the realistic view that very little other than calorie restriction and exercise actually does reliably extend life in mice if you go about the studies carefully. This is good science, but it isn’t the road to extended human life spans: it instead has much more to do with understanding the process of aging at a very detailed level. That task is vast and will take a very long time even in this age of computing and biotechnology.

To my eyes the right way to go is the repair approach: build the biotechnologies needed to repair the forms of cellular and molecular damage produced as a side-effect of the normal operation of metabolism, and which clearly distinguish old tissues from young tissues. If you want rejuvenation of the old, a path to adding decades to healthy life, and to eliminate all age-related disease, then repair is the way to go. Fix the damage, don’t just tinker with the engines of life in ways that might possibly slow down damage accumulation just a little. This strategic direction can allow researchers to largely bypass the great complexity of the progression of aging and focus instead on fixing things that are already well known and well cataloged. But I say this a lot, and will continue to do so until more than just a small fraction of the research community agree with me.

Back to mice and lifespan studies: in this day and age institutional research is far from the only way to get things done. Early-stage research is becoming quite cheap as the tools of biotechnology improve, and the global economy allows quality scientific work to be performed in locations that are lot less expensive than the US or Western Europe. We have crowdfunding, the internet, and a supportive community, which means that any group of ambitious researchers can raise a few tens of thousands of dollars and set an established lab in the Ukraine to running a set of mouse lifespan studies. So that happened back in 2013, and has been ongoing since then despite the present geopolitical issues in that part of the world. It is perhaps worth noting that this is the same group that found no effect on longevity from transfusions of young blood plasma into old mice. The studies mentioned below used pre-aged mice, starting at old age as a way to try to discover effects more rapidly, an approach that is fairly widespread.

I am a little mouse and I want to live longer: updates

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Dear contributors, we wish you a happy New Year! We are sorry to be taken by a very-expected but very time-consuming c60 lifespan study to digest the data in a way to make the long report we had announced. So, for the New Year and in order for you not to wait longer, please find at least the main results so far:

1) 23 months old C57BL6 mice received a mixture of 6 therapies that had already been reported to extend the lifespan of mice: Aspirin; Everolimus (mTOR inhibitor, similar action as rapamycin); Metoprolol (beta blocker); Metformin (anti-diabetic drug); Simvastatin (lowers LDL cholesterol); Ramipril (ACE inhibitor).

The drugs were given in the food, at doses that had been reported to extend lifespan … when taken individually. Some people are given that combination of medicines so we hoped that the drug interaction would not be too damaging, and we had wondered if some lifespan synergy within some of these drugs could lead to an overall high lifespan (e.g. if the different drugs improve different functions). But we observed a lifespan reduction in males and in females.

2) In the food of some remaining females we mixed low doses of 4 medications against cardiovascular conditions: Simvastatin; Thiazide (lowers blood pressure); Losartan potassium (angiotensin receptor blocker, lowers blood pressure); Amlodipine (calcium channel blocker, lowers blood pressure).

The question was: taken at a low-to-medium dose, could these drugs that many aged persons take have some overall preventive effect? We transposed to mice an ongoing polypill clinical trial in the UK, using a basic human-mouse conversion scale. Again, a decrease in lifespan was observed.

3) Adaptations of the first combination of drugs actually extended lifespan!

We started at age 18 months instead of 23 months, reduced the dose (as a function of weight) and gave a) the 6 compounds b) ‘only’ aspirin+metformin+everolimus. The results are to be analysed in greater details as we haven’t analyzed the latest data yet. Also, whatever the refined analysis, we would already like to indicate that it would be good to reproduce the experiment in some other conditions, e.g. hybrid mice; in particular as the mortality rates of these mice was higher than the first series (but in a consistent way that supports the life extending effect).

4) Ongoing C60 experiments

After many difficulties in setting the experiment (cross-border transportation in current geopolitical times, checking absorption in mice/ detecting C60/correct source of C60, administration tried in food and replaced by gavage, training for gavage and various measures) we have transposed the popular lifespan test with c60 fullerenes reported in rats by Baati et al. to mice (CBA strain, common in the lab) and with more animals (N=17 per group). There are three groups (gavage of water, of olive oil, of C60 dissolved in olive oil), there are … a lot of health measures and a lot of gavage (at the beginnings of the experiment as administrations are first very frequent and then gradually less frequent). Given that the experiment starts with mid-aged animals, the results are expected for the beginning of 2016.

The original C60 results from a few years back were greeted with some skepticism in the research community, given the very large size of the effect claimed and the small number of animals tested. There was, I think, also a certain annoyance: now that someone had made what was on the face of it an unlikely claim of significant lifespan extension via administration of C60, then some other group was going to have to waste their time in disproving it. We’ll see how that all turns out, I suppose. This is science as it works in practice.

At some point the broad structural classes of research illustrated by the Interventions Testing Program and this crowdfunded mouse study will meet in the middle, and the process of funding and organizing scientific programs will be a far more complicated, dynamic, and public affair than is presently the case. I think this will be for the better. All that we have we owe to science, and a majority of the public thinks all too little of the work that will determine whether they live in good health or suffer and die a few decades from now. The more they can see what is going on, the better for all of us in the end, I think.

Reason is the founder of The Longevity Meme (now Fight Aging!). He saw the need for The Longevity Meme in late 2000, after spending a number of years searching for the most useful contribution he could make to the future of healthy life extension. When not advancing the Longevity Meme or Fight Aging!, Reason works as a technologist in a variety of industries. 
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This work is reproduced here in accord with a Creative Commons Attribution license. It was originally published on FightAging.org.

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Our Cells Will Be Guided and Protected by Machines – Article by Reason

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Categories: Science, Technology, Transhumanism, Tags: , , , , , , , , , , , , , , ,

The New Renaissance Hat
Reason
September 21, 2014
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A gulf presently lies between the nanoscale engineering of materials science on the one hand and the manipulation and understanding of evolved biological machinery on the other. In time that gulf will close: future industries will be capable of producing and controlling entirely artificial machines that integrate with, enhance, or replace our natural biological machines. Meanwhile biologists will be manufacturing ever more artificial and enhanced versions of cellular components, finding ways to make them better: evolution has rarely produced the best design possible for any given circumstance. Both sides will work towards one another and eventually meet in the middle.

Insofar as aging goes, a process of accumulating damage and malfunction in our biology, it is likely that this will first be successfully addressed and brought under medical control by producing various clearly envisaged ways to repair and maintain our cells just as they are: remove the damage, restore youthful function, and repeat as necessary. We stand much closer to that goal than the far more ambitious undertaking of building a better, more resilient, more easily repaired cell – a biology 2.0 if you like. That will happen, however. Our near descendants will be as much artificial as natural, and more capable and healthier for it.

The introduction of machinery to form a new human biology won’t happen all at once, however, and it isn’t entirely a far future prospect. There will be early gains and prototypes, the insertion of simpler types of machine into our cells for specific narrow purposes: sequestering specific proteins or wastes, or as drug factories to produce a compound in response to circumstances, or any one of a number of other similar tasks. If you want to consider nanoparticles or engineered assemblies of proteins capable of simple decision tree operations as machines then this has already happened in the lab:

Researchers Make Important Step Towards Creating Medical Nanorobots

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Researchers [have] have made an important step towards creating medical nanorobots. They discovered a way of enabling nano- and microparticles to produce logical calculations using a variety of biochemical reactions. Many scientists believe logical operations inside cells or in artificial biomolecular systems to be a way of controlling biological processes and creating full-fledged micro-and nano-robots, which can, for example, deliver drugs on schedule to those tissues where they are needed.

Further, there is a whole branch of cell research that involves finding ways to safely introduce ever larger objects into living cells, such as micrometer-scale constructs. In an age in which the state of the art for engineering computational devices is the creation of 14 nanometer features, there is a lot that might be accomplished in the years ahead with the space contained within a 1000 nanometer diameter sphere.

Introducing Micrometer-Sized Artificial Objects into Live Cells: A Method for Cell-Giant Unilamellar Vesicle Electrofusion

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Direct introduction of functional objects into living cells is a major topic in biology, medicine, and engineering studies, since such techniques facilitate manipulation of cells and allows one to change their functional properties arbitrarily. In order to introduce various objects into cells, several methods have been developed, for example, endocytosis and macropinocytosis. Nonetheless, the sizes of introducible objects are largely limited: up to several hundred nanometers and a few micrometers in diameter. In addition, the uptake of objects is dependent on cell type, and neither endocytosis nor macropinocytosis occur, for example, in lymphocytes. Even after successful endocytosis, incorporated objects are transported to the endosomes; they are then eventually transferred to the lysosome, in which acidic hydrolases degrade the materials. Hence, these two systems are not particularly suitable for introduction of functionally active molecules and objects.To overcome these obstacles, novel delivery systems have been contrived, such as cationic liposomes and nanomicelles, that are used for gene transfer; yet, only nucleic acids that are limited to a few hundred nanometers in size can be introduced. By employing peptide vectors, comparatively larger materials can be introduced into cells, although the size limit of peptides and beads is approximately 50nm, which is again insufficient for delivery of objects, such as DNA origami and larger functional beads.

Here, we report a method for introducing large objects of up to a micrometer in diameter into cultured mammalian cells by electrofusion of giant unilamellar vesicles (GUVs). We prepared GUVs containing various artificial objects using a water-in-oil emulsion centrifugation method. GUVs and dispersed HeLa cells were exposed to an alternating current (AC) field to induce a linear cell-GUV alignment, and then a direct current (DC) pulse was applied to facilitate transient electrofusion.

With uniformly sized fluorescent beads as size indexes, we successfully and efficiently introduced beads of 1 µm in diameter into living cells along with a plasmid mammalian expression vector. Our electrofusion did not affect cell viability. After the electrofusion, cells proliferated normally until confluence was reached, and the introduced fluorescent beads were inherited during cell division. Analysis by both confocal microscopy and flow cytometry supported these findings. As an alternative approach, we also introduced a designed nanostructure (DNA origami) into live cells. The results we report here represent a milestone for designing artificial symbiosis of functionally active objects (such as micro-machines) in living cells. Moreover, our technique can be used for drug delivery, tissue engineering, and cell manipulation.

Cell machinery will be a burgeoning medical industry of the 2030s, I imagine. To my eyes the greatest challenge in all of this is less the mass production of useful machines per se, and more the coordination and control of a body full of tens of trillions of such machines, perhaps from varied manufacturers, introduced for different goals, and over timescales long in comparison to business cycles and technological progress. That isn’t insurmountable, but it sounds like a much harder problem than those inherent in designing these machines and demonstrating them to be useful in cell cultures. It is a challenge on a scale of complexity that exceeds that of managing our present global communications network by many orders of magnitude. If you’ve been wondering what exactly it is we’ll be doing with the vast computational power available to us in the decades ahead, given that this metric continues to double every 18 months or so, here is one candidate.

Reason is the founder of The Longevity Meme (now Fight Aging!). He saw the need for The Longevity Meme in late 2000, after spending a number of years searching for the most useful contribution he could make to the future of healthy life extension. When not advancing the Longevity Meme or Fight Aging!, Reason works as a technologist in a variety of industries. 
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This work is reproduced here in accord with a Creative Commons Attribution license. It was originally published on FightAging.org.

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An Overview of Involuntary Bodily Functions and Cellular Regeneration (2004) – Article by G. Stolyarov II

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The New Renaissance Hat
G. Stolyarov II
July 26, 2014
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Note from the Author: This essay was originally written in 2004 and published on Associated Content (subsequently, Yahoo! Voices) in 2007.  The essay earned over 4,700 page views on Associated Content/Yahoo! Voices, and I seek to preserve it as a valuable resource for readers, subsequent to the imminent closure of Yahoo! Voices. Therefore, this essay is being published directly on The Rational Argumentator for the first time.  
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~ G. Stolyarov II, July 26, 2014
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Two of the mechanisms essential to sustaining human life as we know it are the brain’s coordination of involuntary bodily activities and cellular regeneration. This paper explores such phenomena.
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The brain is responsible for coordinating all involuntary bodily mechanisms, which, in themselves, occupy a far greater amount of the body’s functions than conscious activities. This involuntary activity includes facilitating digestion of food, the movement of muscles, and the reception of sensory signals, and responses such as pain, hunger, or the adrenaline rush.

At present, my brain is facilitating my capacity to see, though the specific items I concentrate are determined by my personal choice. I may choose to touch the keyboard, but the sensation this creates on the tips of my fingers is engineered by the brain without my consent. My heart beats involuntarily; I would not be able to engage in many other activities if I were forced to consciously guide it through its every motion.

The majority of human cells regenerate both to repair damage to a given tissue and to ensure a lifespan beyond that of the given cells. Since human beings will inevitably suffer from a wide variety of minor harms and accidents throughout their lives, it is useful for the body to possess the ability to partially repair itself.

The walls of the stomach, after being eroded by stomach acid, can grow back to their former thickness. A cut can heal by the generation of new skin cells. In the event that white blood cells suffer heavy casualties when resisting microbes, new ones can take their place. These cells are generally short-lived and last for a few years at the most. They must be replaced in order for the human organism to continue existing for decades.

If heart and nerve cells possessed the ability to regenerate, two of the leading causes of “natural” death, brain atrophy and heart failure, would be eliminated, as new vitality would be imparted upon these organs by successive creation of new cells to take the place of old and declining ones.

There are no apparent negative drawbacks to the regeneration of heart cells, but the regeneration of nerve cells may hold the potential of memory loss. If a particular neuron in the brain were responsible for storing a particular datum of information, that datum might be lost once that cell atrophied, though the organism could continue functioning and acquiring new information by the use of the fresh neuron that would arise in the old one’s place.

Of course, in a technological society, where forgotten information can quickly be recalled by the reading of books or the viewing of audiovisual records of multiple varieties, this drawback would not be substantial to bring about complete amnesia or loss of personality within the individual.

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Another View of Aging Science: That We Don’t Know Enough – Article by Reason

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The New Renaissance Hat
Reason
June 27, 2014
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Early this month I pointed out an example of the viewpoint on aging research that focuses on drugs, lifestyle, and metabolic manipulation and sees present work in that area to be a matter of significant and ongoing process. I disagree, for reasons that were explained in that post. Today, I’ll take a glance at a different view of the science of aging and longevity, one that is far more popular in the mainstream research community, and with which I also vehemently disagree.

Researchers in this field might be loosely divided into three camps, which are as follows ordered from largest to smallest: (a) those who study aging as a phenomenon without seeking to produce treatments, (b) those who see to slow aging through development of means to alter the operation of metabolism, such as calorie restriction mimetic drugs, and (c) those who aim to produce rejuvenation biotechnology capable of reversing aging. The vast majority of the aging research community at present consider that too little is known of the details of the progression of aging to make significant inroads in the design of treatments, and that the way forward is fundamental research with little hope of meaningful application for the foreseeable future. This attitude is captured here:

Let me ask you this: ‘Why can’t we cure death yet?’

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We can’t ‘cure death’ because biology is extremely complicated. Without a fundamental understanding of how biological organisms work on a molecular level, we’re left to educated guesses on how to fix things that are breaking in the human body. Trying to cure disease without a full understanding of the underlying principles is like trying to travel to the moon without using Newton’s laws of motion.

The reason we haven’t cured death is because we don’t really understand life.

This is only half true, however. It is true if your goal is to slow down aging by engineering metabolism into a new state of safe operation in which the damage of aging accumulates more slowly. This is an enormous project. It is harder than anything that has been accomplished by humanity to date, measured on any reasonable scale of complexity. The community has only a few footholds in the vast sea of interactions that make up the progression of metabolism and damage through the course of aging, and this is despite the fact that there exists an easily obtained, very well studied altered state of metabolism that does in fact slow aging and extend life. Calorie restriction can be investigated in almost all laboratory species, and has been the subject of intense scrutiny for more than a decade now. Yet that barely constitutes a start on the long road of figuring out how to replicate the effects of calorie restriction on metabolism, let alone how to set off into the unknown to build an even better metabolic state of operation.

Listing these concerns is not even to start in on the fact that even if clinicians could perfectly replicate the benefits of calorie restriction, these effects are still modest in the grand scheme of things. It probably won’t add more than ten years to your life, and it won’t rejuvenate the old, nor restore any of their lost functionality. It is a way of slowing down remaining harm, not repairing the harm that has happened. All in all it seems like a poor use of resources.

People who argue that we don’t understand enough of aging to treat it are conveniently omitting the fact that the research community does in fact have a proven, time-tested consensus list of the causes of aging. These are the fundamental differences between old tissue and young tissue, the list of changes that are not in and of themselves caused by any other process of aging. This is the damage that is the root of aging. There are certainly fierce arguments over which of these are more important and how in detail they actually interact with one another and metabolism to cause frailty, disease, and death. I’ve already said as much: researchers are still in the early days of producing the complete map of how aging progresses at the detail level. The actual list of damage and change is not much debated, however: that is settled science.

Thus if all you want to do is produce good treatments that reverse the effects of aging, you don’t need to know every detail of the progression of aging. You just need to remove the root causes. It doesn’t matter which of them are more or less important, just remove them all, and you’ll find out which were more or less important in the course of doing so – and probably faster than those who are taking the slow and stead scholarly route of investigation. If results are what we want to see then instead of studying ever more esoteric little corners of our biology, researchers might change focus on ways to repair the known forms of damage that cause aging. In this way treatments can be produced that actually rejuvenate patients, and unlike methods of slowing aging will benefit the old by reversing and preventing age-related disease.

This is exactly analogous to the long history of building good bridges prior to the modern age of computer simulation and materials science. With the advent of these tools engineers can now build superb bridges, of a quality and size that would once have been impossible. But the engineers of ancient Rome built good bridges: bridges that allowed people to cross rivers and chasms and some of which still stand today. Victorian engineers built better bridges to facilitate commerce that have stood the test of time, and they worked with little more than did the Romans in comparison to today’s technologies. So the aging research community could begin to build their bridges now, we don’t have to wait for better science. Given that we are talking about aging, and the cost of aging is measured in tens of millions of lives lost and hundreds of millions more left suffering each and every year, it is amazing to me that there are not more initiatives focused on taking what is already known and settled about the causes of aging and using that knowledge to build rejuvenation treatments.

What we see instead is a field largely focused on doing nothing but gathering data, and where there are researchers interesting in producing treatments, they are almost all focused on metabolic engineering to slow aging. The long, hard road to nowhere helpful. Yet repairing the known damage of aging is so very obviously the better course for research and development when compared to the prospect of an endless exploration and cataloging of metabolism. If we want the chance of significant progress towards means of treating aging in our lifetime, only SENS and other repair-based approaches have a shot at delivering. Attempts to slow aging are only a distraction: they will provide a growing flow of new knowledge of our biochemistry and the details of aging, but that knowledge isn’t needed in order to work towards effective treatments for aging today.

Reason is the founder of The Longevity Meme (now Fight Aging!). He saw the need for The Longevity Meme in late 2000, after spending a number of years searching for the most useful contribution he could make to the future of healthy life extension. When not advancing the Longevity Meme or Fight Aging!, Reason works as a technologist in a variety of industries. 
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This work is reproduced here in accord with a Creative Commons Attribution license. It was originally published on FightAging.org.

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A Speculative Order of Arrival for Important Rejuvenation Therapies – Article by Reason

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Categories: Science, Technology, Tags: , , , , , , , , , , , , , , , , , , , , , , ,

The New Renaissance Hat
Reason
October 6, 2012
Recommend this page.
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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 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.

4) Reversing Stem Cell Aging

The stem cell research field is on a collision course with the issue of stem cell aging. Most of the medical conditions that are best suited to regenerative medicine, tissue engineering, and similar cell based therapies are age-related, and thus most of the patients are old. In order for therapies to work well, there must be ways to work around the issues caused by the aged biochemistry of the patient. To achieve this end, the research community will essentially have to enumerate the mechanisms by which stem cell populations decline and fail with age, and then reverse their effects.

Where stem cells themselves are damaged by age, stem cell populations will have to be replaced. This is already possible for many different types of stem cell, but there are potentially hundreds of different types of adult stem cell – and it is too much to expect for the processes and biochemistry to be very similar in all cases. A great deal of work will remain to be accomplished here even after the first triumphs involving hearts, livers, and kidneys.

Much of the problem, however, is not the stem cells but rather the environment they operate within. This is the bigger challenge: picking out all the threads of signalling, epigenetic change, and cause and effect that leads to quieted and diminished stem cell populations – and the resulting frailty as tissues are increasingly poorly supported. This is a fair sized task, and little more than inroads have been made to date – a few demonstrations in which one stem cell type has been coerced into acting with youthful vigor, and a range of research on possible processes and mechanisms to explain how an aging metabolism causes stem cells to slow down and stop their work.

The stem cell research community is, however, one of the largest in the world, and very well funded. This is a problem that they have to solve on the way to their declared goals. What I would expect to see here is for a range of intermediary stopgap solutions to emerge in the laboratory and early trials over the next decade. These will be limited ways to invigorate a few aged stem cell populations, intended to be used to boost the effectiveness of stem cell therapies for diseases of aging.

Any more complete or comprehensive solution for stem cell aging seems like a longer-term prospect, given that it involves many different stem cell populations with very different characteristics.

5) Clearing Advanced Glycation Endproducts (AGEs)

AGEs cause inflammation and other sorts of mischief through their presence, and this builds up with age. Unfortunately, research on breaking down AGEs to remove their contribution to degenerative aging has been a very thin thread indeed over the past few decades: next to no-one works on it, despite its importance, and very little funding is devoted to this research.

Now on the one hand it seems to be the case that one particular type of AGE – glucosepane – makes up 90% or more the AGEs in human tissues. On the other hand, efforts to find a safe way to break it down haven’t made any progress in the past decade, though a new initiative was launched comparatively recently. This is an excellent example of how minimally funded research can be frustrating: a field can hover just that one, single advance away from largely solving a major problem for years on end. All it takes is the one breakthrough, but the chances of that occurring depend heavily on the resources put into the problem: how many parallel lines of investigation can be followed, how many researchers are working away at it.

This is an excellent candidate for a line of research that could move upward in the order of arrival if either a large source of funding emerged or a plausible compound was demonstrated to safely and aggressively break down glucospane in cell cultures. There is far less work to be done here than to reverse stem cell aging, for example.

6) Clearing Aggregates and Lysomal Garbage

All sorts of aggregates build up within and around cells as a result of normal metabolic processes, causing harm as they grow, and the sheer variety of these waste byproducts is the real challenge. They range from the amyloid that features prominently in Alzheimer’s disease through to the many constituents of lipofuscin that clog up lysosomes and degrade cellular housekeeping processes. At this point in the advance of biotechnology it remains the case that dealing with each of the many forms of harmful aggregate must be its own project, and so there is a great deal of work involved in moving from where we stand today to a situation in which even a majority of the aggregates that build up with age can be removed.

The most promising lines of research to remove aggregates are immunotherapy, in which the immune system is trained or given the tools to to consume and destroy a particular aggregate, and medical bioremediation, which is the search for bacterial enzymes that can be repurposed as drugs to break down aggregates within cells. Immunotherapy to attack amyloid as a treatment for Alzheimer’s is a going concern, for example. Biomedical remediation is a younger and far less funded endeavor, however.

My expectation here is that some viable therapies for some forms of unwanted and harmful metabolic byproducts will emerge in the laboratory over the next decade, but that will prove to be just the start on a long road indeed. From here it’s hard for me to guess at where the 80/20 point might be in clearing aggregates: successfully clearing the five most common different compounds? Or the ten most common? Or twenty? Lipofuscin alone has dozens of different constituent chemicals and proteins, never mind the various other forms of aggregate involved in specific diseases such as Alzheimer’s.

But work is work: it can be surmounted. Pertinently, and again, the dominant issue in timing here is the lack of funding and support for biomedical remediation and similar approaches to clearing aggregates.

Reason is the founder of The Longevity Meme (now Fight Aging!). He saw the need for The Longevity Meme in late 2000, after spending a number of years searching for the most useful contribution he could make to the future of healthy life extension. When not advancing the Longevity Meme or Fight Aging!, Reason works as a technologist in a variety of industries.  

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