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New Clinical Study May Be the World’s First Cure for Alzheimer’s Disease – Press Release from Libella Gene Therapeutics

New Clinical Study May Be the World’s First Cure for Alzheimer’s Disease – Press Release from Libella Gene Therapeutics

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Libella Gene Therapeutics


ORLANDO, Fla.Jan. 10, 2018 /PRNewswire/ — Libella Gene Therapeutics LLC will conduct an OUS (outside the United States) clinical trial in Cartagena, Colombia, using gene therapy to reverse age-related diseases, starting with Alzheimer’s. Unlike traditional drugs, which tend to be taken for months or years at a time, gene therapy interventions are intended to be one-off treatments that tackle a disease at its source, repairing faulty DNA and allowing the body to fix itself.

Every day 228 Americans die from Alzheimer’s disease, and there is currently no known treatment or cure. Gene therapy offers the ability to permanently correct a disease at its most basic level, the genome, and could offer cures for many conditions that are currently considered incurable. According to Dr. Bill Andrews, the scientist leading the study, “Human telomerase reverse transcriptase (hTERT) is an enzyme whose expression plays a role in cellular aging and is normally repressed in cells, resulting in progressive shortening of telomeres. Telomerase gene therapy in adult and old mice delays aging and increases longevity without increasing cancer.”

By inducing telomerase, Dr. Andrews and Libella Gene Therapeutics hope to lengthen telomeres in the body’s cells. The clinical trial will treat a limited number of patients using the gene therapy treatment, which has been demonstrated as safe, with minimal adverse reactions in over 186 clinical trials.

Dr. Andrews has been featured in Popular Science, on the “Today” show and in numerous documentaries on the topic of life extension. As one of the principal discoverers of both the RNA and protein components of human telomerase, Dr. Andrews was awarded second place as “National Inventor of the Year” in 1997. He earned a Ph.D. in molecular and population genetics at the University of Georgia in 1981. He has served in multiple senior science and technology roles at leading bioscience corporations. Dr. Andrews is a named inventor on over 50 U.S.-issued patents on telomerase and is the author of numerous scientific research studies published in peer-reviewed scientific journals.

On why the company decided to conduct its clinical research project outside the United States, Libella Gene Therapeutics president Dr. Jeff Mathis said, “Traditional clinical trials in the U.S. can take years and millions — or even billions — of dollars. The research and techniques that have been proven to work are ready now. We believe we have the scientist, the technology, the physicians, and the lab partners that are necessary to get this trial done faster in Colombia.”

The clinical trial is prepping to begin in the first quarter of 2018 and will be conducted at MediHelp Services Clinic in beautiful and tourist-friendly Cartagena, Colombia. The state-of-the-art facility has hosted international public figures including athletes, celebrities and politicians. Dr. Javier Hernandez, MediHelp’s medical director, will oversee the trial.

Colombia’s clinical research regulation is friendly to gene therapy trials, with one of the fastest approval times in Latin America for this kind of research. The trial’s clinical study design; regulatory, operation and logistical support; project management; statistical analysis; and study monitoring services will be provided by LATAM Market Access Inc., a Florida-based clinical research company.

About Libella Gene Therapeutics LLC 
With a mission to reverse aging and cure all age-related diseasesstarting with Alzheimer’sLibella Gene Therapeutics has exclusively licensed the AAV Reverse (hTERT) transcriptase enzyme technology from Sierra Sciences and Dr. Bill Andrews. More information at www.libellagenetherapeutics.com.

About LATAM Market Access Inc.
Dedicated to helping innovative life science companies gather cost-effective clinical data at leading research institutions, the company provides clinical study design; regulatory, operational and logistics support; project management; statistical analysis; and study monitoring services. More information at www.latammarketaccess.com.

 

For the Last Time: Rejuvenation is Not Immortality – Article by Nicola Bagalà

For the Last Time: Rejuvenation is Not Immortality – Article by Nicola Bagalà

Nicola Bagalà


Editor’s Note: In this article, Mr. Nicola Bagalà explains to us the terms “rejuvenation”  and “immortality” and how they should not be construed to mean one and the same.  This article was originally published by the Life Extension Advocacy Foundation (LEAF).

                   ~ Kenneth Alum, Director of  Publication, U.S. Transhumanist Party, January 10, 2018

When doing science, it is crucially important to have clear, unambiguous definitions. These definitions must be firmly established to avoid confusion and misunderstandings and possibly to prevent people from going around telling everyone that you’re working on something that you’re actually not.

The I-word

It’s not uncommon, especially for outsiders of a given field, to use an inappropriate word to indicate a more complex concept than the word itself conveys—maybe because they think that the two are close enough or possibly because they just don’t see the difference.

For this reason, it’s likely that each field has its own unspeakably profane word; in the field of rejuvenation, that word is the dreaded I-word: immortality.

Before I explain why it is a dreaded word, it’s important to define what the heck it even means. Now, of course definitions are entirely arbitrary, and the same word could mean a different thing to a different person; but if we go with the most intuitive, commonly accepted meaning of “immortality” when nothing else is specified, then we can safely say it describes the quality of someone who cannot die. In other words, it refers to an immortal being could not be killed or die in any way, even if it wanted to. Just like people today who would like to live for an indefinitely long time (like me) are forced to eventually die by aging and are thus stuck without a choice (at least until we figure rejuvenation out), a hypothetical immortal being would be in a similar situation, with no choice to terminate its life because its immortality would force it to live forever. This brief article explains the issue very nicely and concisely.

Now, the way I approach life, immortality wouldn’t be all that bad, because I am skeptical that I’d ever have a reason to want to die. Still, I appreciate that I might be wrong, so if I could choose and wanted to play it really safe, I’d opt for an “immortality switch”; as long as it is on, you’re immortal; if and when you get tired of life, you flip it off and you become mortal again, free to get rid of your own life however you see fit.

Unfortunately, an immortality switch is just as improbable as immortality itself. Think about it: to be immortal, your chance of ever dying of any cause at all should be exactly zero. There’d be no gun, no disease, no poison, no amount of air taken out of your lungs, no stellar explosion capable of terminating your existence. The inner workings—biological or not—keeping you alive should be indestructible, able to withstand forces of any magnitude and keep going under any possible circumstance (including running out of energy). Even without dragging the fabled heat death of the universe into the mix, it’s difficult to imagine how any of this could ever be possible—let alone a switch turning this unlikely ability on and off.

What’s the difference?

I’m not going to go as far as to say that the above is completely impossible; I was trained to make such bold claims only when I can prove them, so I’ll just say that, to the best of my knowledge, this sort of immortality appears to be exceedingly unlikely.

Now, whether immortality is possible or not is an intriguing question, but it is decidedly off-topic in the field of rejuvenation, because rejuvenation is not immortality. If a universal antiviral drug able to wipe the floor with every conceivable virus existed, you wouldn’t call it an immortality drug, because right after leaving the doctor’s office where you got your miracle shot, a grand piano might happen to crush you after a 50-story free fall, and the antiviral drug wouldn’t be especially effective against that particular cause of death. Similarly, rejuvenation would save you from death by age-related diseases, but not by falling grand pianos, sadly.

Yet, both people and the media keep talking about “curing death” and “immortality pills” when the actual topic is rejuvenation biotechnology; this is a cause of particular annoyance to Dr. Aubrey de Grey, whose pioneering work is constantly called an “immortality quest” and similar things. Since immortality reasonably seems a pipe dream and is laden with all sorts of ethical issues and concerns, whether justified or not, this results in a gross misrepresentation of the entire field and a lot of unwarranted bashing of completely legitimate medical research whose only fault is that it aims to prevent the diseases of aging rather than just coping with them.

The same story is true of negligible senescence. If a successful rejuvenation platform were implemented, people would still age biologically, but we would have therapies capable of undoing such aging. Through periodic reapplication of these therapies, the hallmarks of aging would always be kept well below the pathology threshold. In other words, we would still senesce (that is, age), but our level of senescence would stay negligible—that’s where the term comes from. Yet, many people keep calling negligible senescence immortality just like they do rejuvenation biotechnology, whether deliberately or by genuine mistake, thereby providing an excellent strawman for needy critics to beat. This is why the I-word is dreaded in this field, by the way.

Negligible senescence is the expected result of truly comprehensive rejuvenation biotechnologies, and yes, if we got there, our healthspan would be vastly increased, and consequently, so would our lifespan; if you were in perfect health for longer than, say, 100 years, it is a disarmingly trivial consequence that you would live for longer than 100 years. However, whether a negligibly senescent person then lives on forever or not, or ten thousand years from now, someone beats the odds and comes up with a fancy immortality switch, is an entirely different matter that is beyond the scope of the field of rejuvenation biotechnology. Speaking of which, let me reiterate once more what its actual scope is: to eradicate age-related diseases. All the rest, whether consequential effects or downright made-up rubbish, is just unnecessary embroidery.

About Nicola Bagalà

Nicola Bagalà has been an enthusiastic supporter and advocate of rejuvenation science since 2011. Although his preferred approach to treating age related diseases is Aubrey de Grey’s suggested SENS platform, he is very interested in any other potential approach as well. In 2015, he launched the blog Rejuvenaction to advocate for rejuvenation and to answer common concerns that generally come with the prospect of vastly extended healthy lifespans. Originally a mathematician graduated from Helsinki University, his scientific interests range from cosmology to AI, from drawing and writing to music, and he always complains he doesn’t have enough time to dedicate to all of them which is one of the reasons he’s into life extension. He’s also a computer programmer and web developer. All the years spent learning about the science of rejuvenation have sparked his interest in biology, in which he’s planning to get a university degree.

About LIFE EXTENSION ADVOCACY FOUNDATION (LEAF)

In 2014, the Life Extension Advocacy Foundation was established as a 501(c)(3) non-profit organization dedicated to promoting increased healthy human lifespan through fiscally sponsoring longevity research projects and raising awareness regarding the societal benefits of life extension. In 2015 they launched Lifespan.io, the first nonprofit crowdfunding platform focused on the biomedical research of aging.

They believe that this will enable the general public to influence the pace of research directly. To date they have successfully supported four research projects aimed at investigating different processes of aging and developing therapies to treat age-related diseases.

The LEAF team organizes educational events, takes part in different public and scientific conferences, and actively engages with the public on social media in order to help disseminate this crucial information. They initiate public dialogue aimed at regulatory improvement in the fields related to rejuvenation biotechnology.

A Review of Immunosenescence – Article by Steve Hill

A Review of Immunosenescence – Article by Steve Hill

Steve Hill


Editor’s Note: In this article, Steve Hill discusses some of the reasons for the decline of the immune system.  This article was originally published by the Life Extension Advocacy Foundation (LEAF).

                   ~ Kenneth Alum, Director of  Publication, U.S. Transhumanist Party, January 9, 2018

Immunosenescence is the age-related decline of the immune system. The reason why our immune systems start to fail and weaken as we age is not fully understood, and, indeed, there are a variety of hypotheses as to why this happens.

Inflammaging

Inflammation certainly plays a role in this process, and it is well documented that inflammation has a considerable effect on immune cells such as macrophages, causing them to become dysfunctional and stop cleaning house. This is in line with the proposed concept of “inflammaging”, which describes an ever-increasing chronic background of inflammation from sources such as senescent cells, cell debris, and changes in the gut microbiota. This inflammaging then drives immune system dysfunction, which then creates more inflammation, continuing a downward spiral.

We recently learned that inflammation can cause problems with weight control by causing nerve-associated macrophages to stop signaling fat cells to release their stored energy[1]. We also know that macrophage dysfunction occurs in other tissues due to inflammation, and so it seems clear that inflammation plays at least a partial role in immune system decline.

Cellular Senescence

Some research suggests that the immune system declines due to its cells becoming senescent, just as other cell populations do. Over time, our cells reach their maximum number of divisions, or they are damaged and enter senescence and destroy themselves via apoptosis, a kind of programmed self-destruct sequence.

However, sometimes these cells resist apoptosis and cling on to life, but in doing so, they prevent fresh cells replacing them while generating inflammatory signals that cause nearby cells to become dysfunctional, too. It is proposed that the immune system experiences the same senescence as our other cells, leading to immune system failure.

Stem-cell depletion

Another player in immune system decline is stem-cell depletion; for example, the thymus begins to shrink from an early age and eventually stops producing new T cells to help defend us from invading pathogens. The production of T cells is facilitated by thymic stem cells, which are gradually depleted over our lifetime, and eventually, we have so few T cells that we cannot fight off diseases such as flu and pneumonia, which often kill the elderly. Some attempts are currently being made to rejuvenate the thymus and have enjoyed some success.

A review of immunosenescence

It is likely the case that immunosenescence is a combination of all of these proposed things and more, and each plays a role in the resulting decline of our immune systems as we age. When it comes to establishing the exact chain of events that leads to immunosenescence, it will take reversing each of those causes to see what happens.

Today, we wanted to bring your attention to an open-access paper that reviews the current knowledge of immunosenescence and provides a good introduction to the topic[2].

Conclusion

Developing the therapies that target the aging processes directly is likely the most expedient path to understanding immunosenescence, as these therapies will give us the tools with which to discover what drives the process. Approaches such as thymic rejuvenation or creating a replacement thymus, replacing lost stem-cell populations such as hematopoietic stem cells that create all immune cells, removing overspecialized immune cells, and removing senescent cells are all valid approaches towards discovering how immunosenescence works.

Our knowledge is growing rapidly by the passing month, and more and more is being understood about the aging processes and how we might directly target them to prevent or reverse age-related diseases. It is almost certain that medicine is going to change dramatically in the next decade or two as our understanding grows.

Literature

[1] Camell, C. D., Sander, J., Spadaro, O., Lee, A., Nguyen, K. Y., Wing, A., … & Rodeheffer, M. S. (2017). Inflammasome-driven catecholamine catabolism in macrophages blunts lipolysis during ageing. Nature, 550(7674), 119-123.

[2] Ventura, M. T., Casciaro, M., Gangemi, S., & Buquicchio, R. (2017). Immunosenescence in aging: between immune cells depletion and cytokines up-regulation. Clinical and Molecular Allergy, 15(1), 21.

About Steve Hill

As a scientific writer and a devoted advocate of healthy longevity technologies, Steve has provided the community with multiple educational articles, interviews, and podcasts, helping the general public to better understand aging and the means to modify its dynamics. His materials can be found at H+ Magazine, Longevity Reporter, Psychology Today, and Singularity Weblog. He is a co-author of the book Aging Prevention for All – a guide for the general public exploring evidence-based means to extend healthy life (in press).

About LIFE EXTENSION ADVOCACY FOUNDATION (LEAF)

In 2014, the Life Extension Advocacy Foundation was established as a 501(c)(3) non-profit organization dedicated to promoting increased healthy human lifespan through fiscally sponsoring longevity research projects and raising awareness regarding the societal benefits of life extension. In 2015 they launched Lifespan.io, the first nonprofit crowdfunding platform focused on the biomedical research of aging.

They believe that this will enable the general public to influence the pace of research directly. To date they have successfully supported four research projects aimed at investigating different processes of aging and developing therapies to treat age-related diseases.

The LEAF team organizes educational events, takes part in different public and scientific conferences, and actively engages with the public on social media in order to help disseminate this crucial information. They initiate public dialogue aimed at regulatory improvement in the fields related to rejuvenation biotechnology.

The Link Between Cellular Senescence and Cellular Reprogramming – Article by Steve Hill

The Link Between Cellular Senescence and Cellular Reprogramming – Article by Steve Hill

Steve Hill


Editor’s Note: In this article, Steve Hill discusses the link between Cellular Senescence and Cellular Reprogramming.  This article was originally published by the Life Extension Advocacy Foundation (LEAF).

            ~ Kenneth Alum, Director of  Publication, U.S. Transhumanist Party, January 8, 2018

The reprogramming of cells is a well-established technique in medicine and has been for over a decade now. It allows the en masse creation of patient-matched cells and is the basis for multiple current therapies.

Cellular Senescence and Cellular Reprogramming share mechanisms

Induced pluripotent stem cells (also known as iPS cells or iPSCs) can be created directly from adult cells. The iPSC technology was pioneered by Shinya Yamanaka, who demonstrated in 2006 that the introduction of four specific genes encoding transcription factors could convert adult cells into pluripotent stem cells[1]. These factors are Oct4, Sox2, Klf4, and c-Myc (OSKM), or as many call them, the Yamanaka factors.

Today, we have a new paper that discusses how induced pluripotency and cellular senescence, two of several possible cellular states, share similarities[2]. It is likely no surprise that the two states are closely related and that some of the mechanisms for one process are shared by the other. It appears that certain key signaling molecules are important in determining both cell fate and senescence.

Controlling cell behavior in living animals

As our understanding of guiding cell fate grows rapidly by the passing year, it has huge implications for therapies that seek to control cellular activities and encourage certain types of cells to be created. Research is now starting to move beyond the petri dish and to where cells are being programmed in situ in living animals.

In 2013, the Hallmarks of Aging proposed that epigenetic changes are a primary reason we age, but, at the time, the evidence in living animals was lacking[3]. All this changed in late 2015 when researchers induced pluripotency in living animals using the OSKM reprogramming factors, in much the same way as iPSC technology creates on-demand cell types outside the body. In this case, they only very briefly induced OSKM so that the aging markers in cells were reset but not long enough to cause the cells to revert to a developmental state.

The results of this first attempt to reprogram cells in living animals resulted in the cells of the mice becoming functionally younger in many ways and increased their healthy lifespan[4]. These results lend yet more support for the hypothesis that epigenetic alterations are one of the reasons we age and that reversing those changes is a path to maintaining health and tissue function as we age. A number of research teams are now exploring cellular reprogramming in living animals with a view to translating this to humans. We discussed the findings of this paper during our monthly Journal Club here.

Conclusion

This paper may be of interest to those wishing to delve deeper into the world of cell fate and understand the connection between cellular senescence and induced pluripotency. This builds on the knowledge we already have, and it is not difficult to imagine a time in the near future when we will have a very high level of control over our cells via reprogramming techniques.

If the hypothesis of epigenetic alterations being one of the causes of aging turns out to be correct, then that would be a real game changer. We are likely not too far off from determining if this is the case or not, and we may have the answer in the next few years, given the current pace of progress.

Literature

[1] Takahashi, K., & Yamanaka, S. (2006). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. cell, 126(4), 663-676.

[2] Mosteiro, L., Pantoja, C., Martino, A., & Serrano, M. (2017). Senescence promotes in vivo reprogramming through p16INK4a and IL‐6. Aging cell.

[3] López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013). The hallmarks of aging. Cell, 153(6), 1194-1217.

[4] Ocampo, A., Reddy, P., Martinez-Redondo, P., Platero-Luengo, A., Hatanaka, F., Hishida, T., … & Araoka, T. (2016). In vivo amelioration of age-associated hallmarks by partial reprogramming. Cell, 167(7), 1719-1733.

About Steve Hill

As a scientific writer and a devoted advocate of healthy longevity technologies, Steve has provided the community with multiple educational articles, interviews, and podcasts, helping the general public to better understand aging and the means to modify its dynamics. His materials can be found at H+ Magazine, Longevity Reporter, Psychology Today, and Singularity Weblog. He is a co-author of the book Aging Prevention for All – a guide for the general public exploring evidence-based means to extend healthy life (in press).

About LIFE EXTENSION ADVOCACY FOUNDATION (LEAF)

In 2014, the Life Extension Advocacy Foundation was established as a 501(c)(3) non-profit organization dedicated to promoting increased healthy human lifespan through fiscally sponsoring longevity research projects and raising awareness regarding the societal benefits of life extension. In 2015 they launched Lifespan.io, the first nonprofit crowdfunding platform focused on the biomedical research of aging.

They believe that this will enable the general public to influence the pace of research directly. To date they have successfully supported four research projects aimed at investigating different processes of aging and developing therapies to treat age-related diseases.

The LEAF team organizes educational events, takes part in different public and scientific conferences, and actively engages with the public on social media in order to help disseminate this crucial information. They initiate public dialogue aimed at regulatory improvement in the fields related to rejuvenation biotechnology.

The Best of the SENS AMA – Article by Steve Hill and Aubrey de Grey

The Best of the SENS AMA – Article by Steve Hill and Aubrey de Grey

Steve Hill

Dr. Aubrey de Grey


Editor’s Note: In this article, Steve Hill highlights the Ask Me Anything on Reddit held on December 7th by Dr. Aubrey de Grey.  This article was originally published by the Life Extension Advocacy Foundation (LEAF).

                   ~ Kenneth Alum, Director of  Publication, U.S. Transhumanist Party, December 13, 2017

 

Dr. Aubrey de Grey from the SENS Research Foundation (SRF) did an Ask Me Anything on Reddit on December 7th, and there were many great questions and answers; we thought it would be a great time to summarize some of the best ones and offer a little commentary.

What do you think were the biggest wins of the last couple of years in SENS-relevant advocacy, research, and development? What has moved the needle?

There have been lots. On the research, I would highlight our paper in Science two years ago, which shows how to synthesize glucosepane, and our paper in Nucleic Acids Research one year ago, which shows simultaneous allotopic expression of two of the 13 mitochondrial genes. Both of those projects have been greatly accelerated in the meantime as a result of those key enabling breakthroughs; watch this space.

On advocacy, I think the main win has been the arrival of private capital; I would especially highlight Jim Mellon and his Juvenescence initiative because he is not only a successful, energetic and visionary investor, he is also a highly vocal giver of investment advice.

We are pleased to have been involved with the second project mentioned here, as we hosted the MitoSENS project at Lifespan.io, where it raised 153% of its initial fundraising goal. Less than a year later, after raising this money, it went on to publish the groundbreaking study showing that backup copies of mitochondrial genes could indeed be created in the nucleus. Dr. de Grey originally proposed the idea over a decade ago amid much scepticism; it is really good to see that years later he has been vindicated. This is the power of crowdfunding and how we as a community can make big changes in science by working together.

How do you feel about the impact of groups like LEAF advocating and reporting on rejuvenation biotech? Has the advocacy and reporting of these groups made your life any easier?

Massively! A huge thing that I say all the time is that advocacy absolutely relies upon the diversity of its messengers. Different people listen to different forms of words, different styles of messaging, etc. The more, the better.

It’s good to know that our work is appreciated and helping. Working together as a community is essential for progress, so it was nice to see this question and response from someone we respect a great deal.

We have said many times before effective advocacy efforts are just as important as the research itself. Professional advocacy has the potential to increase public support and funding, paving the way for the arrival of rejuvenation biotechnology. In the past decade or so, advocacy has mostly been left to volunteers and people such as Dr. de Grey.

Popular causes attract celebrities, public support, funding and investment; if we want a revolution in medicine and how we treat aging, then we must popularize the movement. There has been a serious shortage of full-time and organized advocacy; therefore, we decided to create LEAF to support groups like the SRF, advocate to popularize the cause, and help to raise much-needed funds for research efforts. We are only able to do this thanks to the support of the community, and we are extremely grateful to our Lifespan Heroes for helping us to do the work we do.

Aside from funding, what do you consider to be a burden or delay for your type of research?

Nothing. Seriously, nothing at all. We have the plan, and we have the people. It’s all about enabling those people by giving them the resources to get on with the job.

Indeed, funding for research is one of the four major bottlenecks slowing down the development of therapies that address the aging processes. The more funding the field gets, the more projects can be launched, the sooner breakthroughs can potentially happen, and the greater the benefits will likely be for all of us.

Is there anything new you are able to say about the breaking of cross-links in the extracellular matrix?

Absolutely. Short story, we now have a bunch of glucosepane-breaking enzymes, and we are within a few months of spinning the work out into a startup.

A suspected cause of degenerative aging is the accumulation of sugary metabolic wastes known as advanced glycation end-products (AGEs). These are wastes that are, in some cases, hard for our metabolism to break down fast enough or even at all. Some types, such as glucosepane, can form cross-links, gumming together important proteins such as those making up the supporting extracellular matrix scaffold.

The properties of elastic tissues (skin and the blood vessel walls) derive from the particular structure of the extracellular matrix, and cross-links degrade that structure, preventing it from functioning correctly. AGEs’ presence contributes to blood vessel stiffening with age, and it is implicated in hypertension and diabetes.

That SRF now has candidate enzymes is very significant because it means that there are now potential ways to remove these crosslinks from our tissues. There are many types of crosslinks, and we already know of compounds and drugs that can break other kind of crosslinks; the major problem is glucosepane, as it lasts a very long time, and, so far, nothing is known to remove it. Given that other types of crosslinks can be removed, Dr. de Grey rightly thought that there must be ways to remove (cleave) glucosepane from tissues; now, it seems that we are a step closer to that potentially becoming a reality.

If the SRF is successful in finding ways to break glucosepane crosslinks, this has huge implications for diabetes, hypertension and aging. It is great to hear that the organization is now reaching the point at which it is almost time to develop this as a therapy by creating a startup company.

It seems likely that artificial intelligence will be a necessary tool in order to reach longevity escape velocity. I was wondering how much of a role does artificial intelligence play in your research? Is this something you devote many resources to?

We don’t, but that is because other major players in this field (and good friends of mine), such as Alex Zhavoronkov and Kristen Fortney, are doing it so well already (with Insilico Med and BioAge, respectively). Check out the BioData West conference that will occur in SF a couple of days before our Undoing Aging conference in Berlin; I will be chairing a session on this.

We believe that the application of AI and, in particular, machine learning will prove to be a very valuable tool for research in the coming years. Such systems are ideally suited for high-throughput, laborious tasks that also require high attention to detail and would take humans a long time to do. Drug discovery, image analysis and many more tasks in the lab could potentially be automated, saving time and freeing up researchers to work on other critical tasks.

We are proud to have hosted the MouseAge project this year, which is an AI-based visual aging biomarker application that helps researchers determine the age of mice without the use of harmful tests. In a few months, researchers will be able to use the MouseAge application in the lab to help speed research progress up. This is just one example of how AI can be used in aging research and how the community helped to make it happen.

Given current funding, how far away from robust mouse rejuvenation do you think you are?

My estimate is 5-7 years, but that’s not quite “given current funding”. My overoptimism in saying “10 years” 13 years ago consisted entirely of overoptimism about funding – the science itself has not thrown up any nasty surprises whatsoever – but, nonetheless, I am quite optimistic as of now about funding, simply because the progress we have made has led to a whole new world of startups (including spinoffs from the SENS Research Foundation) and investors, so it’s not only philanthropy anymore. Plus, the increase in overall credibility of the approach is also helping to nurture the philanthropic side. We are still struggling, that’s for sure, but I’m feeling a lot surer that the funding drought’s days are numbered than I felt even two or three years ago.

Robust mouse rejuvenation (RMR) has long been a goal for the SENS Research Foundation, going back to when the SENS approach was initially proposed. RMR was originally outlined as being able to demonstrate and replicate SENS to double the remaining life expectancy of an already aged mouse. This would not mean the first RMR would be a total implementation of all the SENS approaches or that rejuvenation would need to be absolute; it would be a first pass to demonstrate the viability of multiple SENS approaches combined to produce robust results.

Being able to achieve a first-pass RMR could do much to convince academia that the repair approach to aging is plausible and attract more funding and interest in the approach. While RMR working in mice may not sound that exciting, it has huge implications for the field and potentially the rate of funding and progress.

How confident are you still in your previous prediction that humans will be able to control aging by 2029?

I think we’ve slipped a few years, entirely because of lack of funding. The tipping point will be when results in mice convince a critical mass of my curmudgeonly, reputation-protecting expert colleagues that rejuvenation will eventually work, such that they start to feel able to say so publicly. I think that’s on the order of five years away.

We think that the tipping point could well be if senolytics have the same result in humans as they have in mice. Enhanced tissue repair and regeneration in older people would be a very strong case for the repair approach to aging and almost certain to convince the academics sitting on the fence.

Certainly, if AGE breakers could be demonstrated to work in humans, this would also go a long way towards not only convincing academia but also grabbing public interest. Removing AGEs from the skin may potentially reverse wrinkles, for example, and restore skin elasticity, offering a very visual demonstration of repair being plausible.

There is almost certainly going to be a tipping point at which the bulk of academic and public support swings in favour of a repair approach to aging; the only question is when? Well, the sooner the basic science can be done and moved to translational research, the sooner we can all potentially benefit from these technologies. This makes supporting both the research and advocacy of rejuvenation biotechnology very important for progress.

 

About Dr. Aubrey de Grey

Dr. Aubrey de Grey is a biomedical gerontologist based in Cambridge, UK and Mountain View, California, USA, and is the Chief Science Officer of SENS Research Foundation, a California-based 501(c)(3) charity dedicated to combating the aging process. He is also Editor-in-Chief of Rejuvenation Research, the world’s highest-impact peer-reviewed journal focused on intervention in aging. He received his BA and Ph.D. from the University of Cambridge in 1985 and 2000 respectively. His original field was computer science, and he did research in the private sector for six years in the area of software verification before switching to biogerontology in the mid-1990s. His research interests encompass the characterisation of all the accumulating and eventually pathogenic molecular and cellular side-effects of metabolism (“damage”) that constitute mammalian aging and the design of interventions to repair and/or obviate that damage. He has developed a possibly comprehensive plan for such repair, termed Strategies for Engineered Negligible Senescence (SENS), which breaks aging down into seven major classes of damage and identifies detailed approaches to addressing each one. A key aspect of SENS is that it can potentially extend healthy lifespan without limit, even though these repair processes will probably never be perfect, as the repair only needs to approach perfection rapidly enough to keep the overall level of damage below pathogenic levels. Dr. de Grey has termed this required rate of improvement of repair therapies “longevity escape velocity”. Dr. de Grey is a Fellow of both the Gerontological Society of America and the American Aging Association, and sits on the editorial and scientific advisory boards of numerous journals and organisations.

About Steve Hill

As a scientific writer and a devoted advocate of healthy longevity technologies, Steve has provided the community with multiple educational articles, interviews, and podcasts, helping the general public to better understand aging and the means to modify its dynamics. His materials can be found at H+ Magazine, Longevity Reporter, Psychology Today, and Singularity Weblog. He is a co-author of the book Aging Prevention for All – a guide for the general public exploring evidence-based means to extend healthy life (in press).

About LIFE EXTENSION ADVOCACY FOUNDATION (LEAF)

In 2014, the Life Extension Advocacy Foundation was established as a 501(c)(3) non-profit organization dedicated to promoting increased healthy human lifespan through fiscally sponsoring longevity research projects and raising awareness regarding the societal benefits of life extension. In 2015 they launched Lifespan.io, the first nonprofit crowdfunding platform focused on the biomedical research of aging.

They believe that this will enable the general public to influence the pace of research directly. To date they have successfully supported four research projects aimed at investigating different processes of aging and developing therapies to treat age-related diseases.

The LEAF team organizes educational events, takes part in different public and scientific conferences, and actively engages with the public on social media in order to help disseminate this crucial information. They initiate public dialogue aimed at regulatory improvement in the fields related to rejuvenation biotechnology.

SENS: Progress in the Fight Against Age-Related Diseases – Article by Nicola Bagalà and Steve Hill

SENS: Progress in the Fight Against Age-Related Diseases – Article by Nicola Bagalà and Steve Hill

Nicola Bagalà

Steve Hill


Editor’s Note: In this article, Mr. Nicola Bagalà and Steve Hill discuss the progress that the SENS Research Foundation has made in tackling the aging processes. Below is a brief summary of some of the highlights of their research efforts.  This article was originally published by the Life Extension Advocacy Foundation (LEAF).

                   ~ Kenneth Alum, Director of  Publication, U.S. Transhumanist Party, December 8, 2017

 

 

Today, there are many drugs and therapies that we take for granted. However, we should not forget that what is common and easily accessible today didn’t just magically appear out of thin air; rather, at some point, it used to be an unclear subject of study on which “more research was needed”, and even earlier, it was just a conjecture in some researcher’s head.

Hopefully, one day not too far into the future, rejuvenation biotechnologies will be as normal and widespread as aspirin is today, but right now, we’re in the R&D phase, so we should be patient and remind ourselves that the fact that we can’t rejuvenate people today doesn’t mean that nothing is being done or has been achieved to that end. On the contrary, we are witnessing exciting progress in basic research—the fundamental building blocks without which rejuvenation, or any new technology at all, would stay a conjecture.

In particular, SENS Research Foundation (SRF), a pioneering organization of the field, is sometimes unjustly accused by skeptics for failing to produce results. But produce results it has, and many at that. Skeptics either decide to ignore them or do not have access to reliable sources. For the benefit of the latter, we’ll discuss below what has been achieved by SRF over the past few years, in relation to the infamous “seven deadly things”, the seven categories of damage that aging causes as described in the SENS repair approach.

Mitochondrial mutations

In a nutshell, a mitochondrion is a cell component that is in charge of converting food nutrients into ATP (adenosine triphosphate), a chemical that powers cellular function. Your DNA is contained within the nucleus of each of your cells, but this isn’t the only DNA in your body; mitochondria have their own DNA (known as mtDNA), likely because, at the dawn of life, they were independent organisms that eventually entered a symbiotic relationship with eukaryotic cells, such as those found in our bodies.

Unfortunately, as mitochondria produce ATP, they also produce so-called free radicals as a byproduct—atoms with unpaired electrons that seek to “pair up” with other electrons, and to do so, they’ll gladly snatch them from other molecules nearby, damaging them. As free radicals are created by mitochondria, they’re very close to mtDNA, which is thus very susceptible to being damaged and undergoing mutations.

Mitochondria with damaged DNA may become unable to produce ATP or even produce large amounts of waste that cells cannot get rid of. To add insult to injury, mutant mitochondria have a tendency to outlive normal ones and take over the cells in which they reside, turning them into waste production facilities that increase oxidative stress—one of the driving factors of aging.

MitoSENS: How to solve this problem, and how far we’ve got

Cell nuclei are far less exposed to free-radical bombardment than mitochondria, which makes nuclear DNA less susceptible to mutations. For this reason, the cell nucleus would be a much better place for mitochondrial genes, and in fact, evolution has driven around 1000 of them there. Through a technique called allotopic expression, we could migrate the remaining genes to the nucleus and solve the problem of mitochondrial mutations.

Human-made allotopic expression was a mere theory until late 2016, when, thanks to the successful MitoSENS crowdfunding campaign on Lifespan.io, a proof of concept was finally completed. Dr. Matthew O’Connor and his team managed to achieve stable allotopic expression of two mitochondrial genes in cell culture, as reported in the open-access paper[1] they published in the journal Nucleic Acids Research. As Aubrey de Grey himself explains in this video, of the 13 genes SRF is focusing on, it’s now managed to migrate almost four. This had never been done before and is a huge step towards addressing this aspect of aging in humans. In the past few months, the MitoSENS team has presented its results around the world and worked on some problems encountered in the project.

A list of SRF-funded papers on the topic of mitochondrial mutations can be found here. A more detailed description of its intramural MitoSENS research can be found here.

Lysosomal dysfunction

Lysosomes are digestive organelles within cells that dispose of intracellular garbage—harmful byproducts that would otherwise harm cells. Enzymes within lysosomes can dispose of most of the waste that normally accumulates within cells, but some types of waste, collectively known as lipofuscin, turn out to be impossible to break down. As a result, this waste accumulates within the lysosomes, eventually making it harder for them to degrade even other types of waste; in a worst-case scenario, overloaded lysosomes can burst open and spread their toxic contents around.

This eventuality is especially problematic for cells that replicate little or not at all, such as heart and nerve cells—they’ve got all the time in the world to become swamped in waste, which eventually leads to age-related pathologies, such as heart disease and age-related macular degeneration.

LysoSENS: How to solve this problem, and how far we’ve got

As normal lysosomal enzymes cannot break down lipofuscin, a possible therapy could equip lysosomes with better enzymes that can do the job. The approach suggested by SRF originates with ERT—enzyme replacement therapy—for lysosomal storage diseases. This involves identifying enzymes capable of breaking down different types of intracellular junk, identifying genes that encode for these enzymes, and finally delivering the enzymes in different ways, depending on the tissues and cell types involved.

SRF funded a preliminary research project on lipofuscin clearance therapeutics at Rice University[2] and another project relating to atherosclerosis and the clearance of 7-ketocholesterol[3] (a lipofuscin subtype), which eventually spun into Human Rejuvenation Biotechnologies, an early-stage private startup funded by Jason Hope.

A LysoSENS-based approach is currently being pursued by Dr. Kelsey Moody, who used to work at SRF. Dr. Moody has been working on an ERT treatment for age-related macular degeneration. The treatment consists in providing cells of the macula (a region of the eye’s retina) with an enzyme capable of breaking down a type of intracellular waste known as A2E. The treatment, called LYSOCLEAR, is being worked on by Moody’s company Ichor Therapeutics, which earlier this year has announced a series A offering to start Phase I clinical trials of its product.

If LYSOCLEAR proves successful, it could pave the way for future LysoSENS-based therapies to treat lysosomal dysfunction in different tissues.

A list of SRF-funded papers on the topic can be found here.

Cellular senescence

As cells divide, their telomeres—the end-parts of chromosomes protecting them from damage—shorten. Once a critical length has been reached, cells stop dividing altogether and enter a state known as senescence. Senescent cells are known to secrete a cocktail of chemicals called SASP (Senescence Associated Secretory Phenotype), which promotes inflammation and is associated with several age-related conditions.

However, senescent cells are a bit of a double-edged sword; as explained by Professor Judy Campisi during RB2016, as long as they’re not too numerous, senescent cells carry out an anti-cancer function and may promote wound healing; however, too many of them have the opposite effect, and on top of that, they induce neighboring cells to undergo senescence themselves, starting a dangerous spiral.

Normally, senescent cells destroy themselves via programmed cell death, known as apoptosis, and are then disposed of by the immune system, but some of them manage to escape destruction, and as the immune system declines with age, this gets worse.

The result is that late in life, senescent cells have accumulated to unhealthy amounts and significantly contribute to the development of age-related diseases. Osteoarthritis, cardiovascular diseases, cancer, metabolic disorders such as diabetes, and obesity are all linked to the chronic age-related inflammation to which senescent cells contribute.

ApoptoSENS: How to solve this problem, and how far we’ve got

The proposed SENS solution is straightforward: if senescent cells become too numerous, then they need to be purged. Since they are useful in small amounts, the optimal solution would be periodically removing excess senescent cells without eradicating them entirely—and more importantly, leaving other cells unharmed.

This could potentially be achieved by either senolytic drugs or gene therapies that selectively target senescent cells and trigger programmed cell death. Indeed, a great deal of recent focus by researchers have been on finding ways to remove senescent cells using senolytic therapies.

Another approach that could complement senolytics is to address why the immune system stops clearing senescent cells effectively in the first place. This approach focuses on macrophages and other immune cells involved in clearing senescent cells, aiming to reduce inflammation so that these cells begin to function properly again. The irony is that as inflammation rises with age, the immune system that is supposed to clear senescent cells and keep inflammation levels down actually starts to create more inflammation and becomes part of the problem by not doing its job properly.

SRF has funded a number of studies on the subject of cellular senescence, and it’s recently begun working on a project in collaboration with the Buck Institute for Research on Aging, which is focusing on the immune system and its role in clearing senescent cells. Another extramural project, again with the Buck Institute, is focussed on SASP inhibition.

Senescent cell clearance has been all the rage for the past two years or so; Lifespan.io has hosted the MMTP project, which focused on testing senolytics in mice, and this was later followed by CellAge’s project to design synthetic biology-based senolytics.

There are other companies that have joined the race to add senescent cell clearance to the standard toolkit of doctors, such as Unity Biotechnology and Oisin Biotechnologies.

Unity’s approach uses a drug-based approach to senolytics and is scheduled to enter human clinical trials in 2018. A number of other research teams are also developing drug-based approaches to removing senescent cells, and the competition looks set to be fierce in this area in the coming years.

Oisin’s approach, which we discussed here, makes use of suicide genes and hopefully will be tested in clinical trials not too far into the future, thanks to venture funding presently being collected. If this system can be made to work, it will allow very selective targeting of senescent cells by destroying only those giving off a target gene or genes. Thus, if a unique gene expression profile for senescent cells is determined, it would mean only those cells were destroyed, with less risk of off-target effects.

Oisin owes its existence to the SENS Research Foundation and the Methuselah Foundation, which provided the necessary seed funding. Kizoo Technology Ventures has also invested in Oisin.

Extracellular crosslinks

The so-called extracellular matrix is a collection of proteins that act as scaffolding for the cells in our body. This scaffolding is rarely if ever replaced, and a really bad consequence of this is that its parts eventually end up being improperly linked to each other through a process called glycation—the reaction of (mainly) blood sugar with the proteins that make up the extracellular matrix itself.

The resulting cross-links impair the function and movement of the linked proteins, ultimately stiffening the extracellular matrix, which makes organs and blood vessels more rigid. Eventually, this leads to hypertension, high blood pressure, loss of skin elasticity, and organ damage, among other problems.

While there are different types of cross-links—known as AGEs, short for advanced glycation end-products—glucosepane is arguably the worst, being the most common and long-lasting of all, and the body is very ill-equipped to break it down.

GlycoSENS: How to solve this problem, and how far we’ve got

In order to eliminate unwanted cross-links, the SENS approach proposes to develop AGE-breaking molecules that may indeed sever the linkages and return tissues to their original flexibility. Of course, in order to do so, crosslink molecules need to be available for research to attempt to combat them with drugs, and especially in the case of glucosepane, this has been a problem for years.

Glucosepane is a very complex molecule, and very little of it can be extracted from human bodies, and not even in its pure form. This has been greatly hampering the progress of research against glucosepane, but thankfully, this problem is now solved thanks to a collaboration between the Spiegel Lab at Yale University and the SENS Research Foundation, which financially supported the study. It is now possible to fully synthesize glucosepane, allowing for researchers to create it on demand and at a cost-effective price.

The Spiegel Lab’s scientists are now developing anti-glucosepane monoclonal antibodies to cleave unwanted cross-links. The collaboration between the Spiegel Lab and SRF dates all the way back to 2011, but it was in 2015 that the Lab announced its success and published a related paper [4] in the journal Science.

Further information on glucosepane cross-link breakers can be found in this interview with Dr. David Spiegel from Yale University on Fight Aging!; a list of studies on the subject funded or otherwise supported by the SRF is available here.

SRF also worked with the Babraham Institute on a cross-link quantification project.

Let’s help SRF move forward

Readers who wish to donate to SRF to help the organization in its crusade against the ill health of old age can do so by contributing to its winter fundraiser or even becoming SRF patrons. Have a look at SRF’s donation page to find out more.

NB: Dr. Aubrey de Grey (Chief Science Officer and Co-founder of SENS Research Foundation) himself held an AMA (“ask me anything”) on Reddit on December 7, at 14:00 PST (22:00 UTC, 17:00 EST). The questions and Dr. de Grey’s responses can be found here.

Literature

[1] Boominathan, A., Vanhoozer, S., Basisty, N., Powers, K., Crampton, A. L., Wang, X., … & O’Connor, M. S. (2016). Stable nuclear expression of ATP8 and ATP6 genes rescues a mtDNA Complex V null mutant. Nucleic acids research, 44(19), 9342-9357.

[2] Gaspar, J., Mathieu, J., & Alvarez, P. (2016). A rapid platform to generate lipofuscin and screen therapeutic drugs for efficacy in lipofuscin removal. Materials, Methods and Technologies, 10, 1-9.

[3] Mathieu, J. M., Wang, F., Segatori, L., & Alvarez, P. J. (2012). Increased resistance to oxysterol cytotoxicity in fibroblasts transfected with a lysosomally targeted Chromobacterium oxidase. Biotechnology and bioengineering, 109(9), 2409-2415.

[4] Draghici, C., Wang, T., & Spiegel, D. A. (2015). Concise total synthesis of glucosepane. Science, 350(6258), 294-298.

 

About Steve Hill

As a scientific writer and a devoted advocate of healthy longevity technologies, Steve has provided the community with multiple educational articles, interviews, and podcasts, helping the general public to better understand aging and the means to modify its dynamics. His materials can be found at H+ Magazine, Longevity Reporter, Psychology Today, and Singularity Weblog. He is a co-author of the book Aging Prevention for All – a guide for the general public exploring evidence-based means to extend healthy life (in press).

About Nicola Bagalà

Nicola Bagalà has been an enthusiastic supporter and advocate of rejuvenation science since 2011. Although his preferred approach to treating age related diseases is Aubrey de Grey’s suggested SENS platform, he is very interested in any other potential approach as well. In 2015, he launched the blog Rejuvenaction to advocate for rejuvenation and to answer common concerns that generally come with the prospect of vastly extended healthy lifespans. Originally a mathematician graduated from Helsinki University, his scientific interests range from cosmology to AI, from drawing and writing to music, and he always complains he doesn’t have enough time to dedicate to all of them which is one of the reasons he’s into life extension. He’s also a computer programmer and web developer. All the years spent learning about the science of rejuvenation have sparked his interest in biology, in which he’s planning to get a university degree.

About LIFE EXTENSION ADVOCACY FOUNDATION (LEAF)

In 2014, the Life Extension Advocacy Foundation was established as a 501(c)(3) non-profit organization dedicated to promoting increased healthy human lifespan through fiscally sponsoring longevity research projects and raising awareness regarding the societal benefits of life extension. In 2015 they launched Lifespan.io, the first nonprofit crowdfunding platform focused on the biomedical research of aging.

They believe that this will enable the general public to influence the pace of research directly. To date they have successfully supported four research projects aimed at investigating different processes of aging and developing therapies to treat age-related diseases.

The LEAF team organizes educational events, takes part in different public and scientific conferences, and actively engages with the public on social media in order to help disseminate this crucial information. They initiate public dialogue aimed at regulatory improvement in the fields related to rejuvenation biotechnology.

We are the Lifespan – Video and Commentary by the Life Extension Advocacy Foundation

We are the Lifespan – Video and Commentary by the Life Extension Advocacy Foundation

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Life Extension Advocacy Foundation


The U.S. Transhumanist Party is pleased to share this message and video from our allies at LEAF – the Life Extension Advocacy Foundation. The video includes a short clip of remarks from U.S. Transhumanist Party Chairman Gennady Stolyarov II, taken from his video for the “I am the Lifespan” campaign.


As you might remember, during the month of October (often called Longevity Month) we at LEAF were accepting videos to hear your reasons why defeating the diseases of aging is so important — and hear from you we did!

Dozens of videos poured in, and this #GivingTuesday we at LEAF are so proud to share with you all a video that shows how strong we can be when we join forces for longer, healthier lives — how together #WeAreTheLifespan.

Thank you so much for raising your voice with us in support of longevity research, and if you wish to continue to help us please feel free to join our Hero campaign or to participate in Facebook’s #GivingTuesday donation match by clicking any of the donate buttons on our Facebook page or posts. If you want to get creative, you can even make your own fundraisers easily on Facebook on posts or with a live video.

Finally, to illustrate the importance of speaking freely on what you care about, we are pleased to let you know of the developments related to the recent Open Consultation on the 13th draft programme of work of the WHO. As we wrote not long ago, the problems related to population aging and corresponding health and social issues were left out of the draft, and we invited the members of the community to step in and recommend an improvement.

90% of responses during the Open Consultation (out of around 400 responses) underlined the need to make healthy longevity one of the priorities for the 13th programme of work, and the WHO have recognized this. A joint effort of many pro-longevity organizations made that happen.

Each voice matters. Your voice matters. So please, keep being active and vocal, and let’s become the generation who can say: “I helped set all people free from age-related diseases. I helped defeat aging.”

Thank you, and happy #GivingTuesday!

Test-Tube Tomato Still-Life – Painting by Ekaterinya Vladinakova

Test-Tube Tomato Still-Life – Painting by Ekaterinya Vladinakova

Ekaterinya Vladinakova


 

“Test-Tube Tomato Still-Life” by Ekaterinya Vladinakova

 

Ekaterinya Vladinakova’s lush work plunges viewers into a vivid vision of the possible future. Friable strokes of dust rush along the barren cracks that mark the Red Planet as depicted in her Test-Tube Tomato Still-Life. Vladinakova examines the basic question of how might humans grow crops and other necessary resources on a planet as desolate as Mars. 

The gleam of the sun’s halo refracts over the surface of a hopeful tomato plant growing within a glass beaker. This may just be one of possibilities actualized once humans overcome the hurdle of successfully arriving on the surface Mars. Harnessing the power of photosynthesis in controlled environments devoid of soil or constant sunlight may prove to be feasibly effective. As one research team from the University of Florida found, plants can fare off pretty well with low light and zero-gravity conditions. Various plants were monitored on the International Space Station orbiting some 350 kilometers above Earth at the time. Researchers observed that the plants monitored showed no signs of impeded growth despite being in an environment devoid of gravity or constant light.

Another possibility is terraforming. With companies like SpaceX leading the mission towards full colonization of Mars, terraforming has been a topic of much debate. Terraforming would include the process of completely manipulating the atmosphere of the planet in order to recreate the ideal conditions of sustaining life. Such a process is arduous and would require a considerable amount of resources to even begin. Yet, it is still a possibility not far from our grasp.

Ekaterinya Vladinakova is an accomplished digital painter. See her gallery here and her DeviantArt page here.

~ Emanuel Iral, Director of Visual Art, U.S. Transhumanist Party, October 31, 2017
Stem-Cell Clinical Trials Show Remarkable Results Against Age-Related Frailty – Article by Steve Hill

Stem-Cell Clinical Trials Show Remarkable Results Against Age-Related Frailty – Article by Steve Hill

Steve Hill


Editor’s Note: In this article, Mr. Steve Hill discusses two very promising human clinical trials using stem cell therapy for age-related frailty. This article was originally published by the Life Extension Advocacy Foundation (LEAF) .

~ Kenneth Alum, Director of Publication, U.S. Transhumanist Party, October 29, 2017

The first results of two human clinical trials using stem cell therapy for age-related frailty have been published, and the results are very impressive indeed. The studies show that the approach used is effective in tackling multiple key age-related factors.

Aging research has made significant progress in the last few years, with senescent-cell-clearing therapies entering human trials this year, DNA repair in human trials, and a number of other exciting therapies nearing human testing. We are reaching the point where therapies that target aging processes are no longer a matter of speculation; they are now an undeniable matter of fact.

What are mesenchymal stem cells?

Mesenchymal stem cells (MSCs) are one of the most commonly used types of stem cells in therapy. MSCs are adult stem cells that can become other types of cells, depending on stimulus; this ability to become a variety of other cell types is known as multipotency. [1]

The cells into which MSCs can transform (differentiate) include osteoblasts (bone cells), chondrocytes (cartilage cells), myocytes (muscle cells), and adipocytes (fat cells). MSCs are of great interest to aging researchers and are arguably one of the most well studied and understood types of stem cells. [2]

MSCs are currently in various trials to treat conditions such as cancer, heart disease, and arthritis. [3] The potential of MSCs for treating neurodegenerative diseases, such as Alzheimer’s, are also being explored in preclinical testing. [4-5]

A therapy for age-related frailty

The focus of the MSC therapy in the case of these two clinical trials is to reduce the effects of age-related frailty on senior citizens. This also marks an important step for rejuvenation biotechnology, as this is the first stem-cell treatment that is close to final FDA approval for specifically targeting age-related frailty. Should this be approved, then it opens the door for other similar approaches and the potential treatment of many age-related diseases.

The therapy itself uses MSCs taken from adult donor bone marrow and is infused into patients with an average age of 76 years old. The good news is that patients in both the phase 1 and phase 2 clinical trials have shown no adverse effects to treatment.

This is excellent news and now paves the way to move to phase 3 clinical trials, which are larger-scale tests to further determine the efficacy and compare it to the best currently available treatments, for which there are basically none beyond simple coping approaches, such as walking sticks and frames to compensate for frailty.

It is also important to note that at this at this point, the drug or therapy is accepted as having some effect. You can read more about the clinical trial process and what each phase means here.

In the first trial, 15 patients with age-related frailty were given a single transplant of MSCs from donors aged between 20 and 45. [6] Six months later, all patients in the trial showed an improved level of fitness, lower levels of inflammatory tumor necrosis factor (TNF), and improved quality of life in general. TNF is one of the regulators of inflammation and contributes to the chronic age-related inflammation known as “inflammaging”, which drives a number of age-related diseases. [7]

The second trial was a randomized, double-blind study including a placebo group. An improved physical performance level was observed in patients, and, again, the level of systemic TNF, and thus inflammation, was reduced. [8] Once again, there were no adverse effects observed in the patients, and the researchers wrote:

Treated groups had remarkable improvements in physical performance measures and inflammatory biomarkers, both of which characterize the frailty syndrome.

David G. Le Couter and colleagues have written about the clinical trials in a guest editorial in The Journals of Gerontology:

There are always caveats associated with interpreting efficacy in small numbers of subjects, yet it is remarkable that a single treatment seems to have generated improvement in key features of frailty that are sustained for many months.

The next step for the researchers here is to begin a phase 2b clinical trial with 120 patients in ten different locations. Following the conclusion of this, a large randomized phase 3 trial will be launched, and this will be the final barrier to public approval for the therapy.

Conclusion

With an ever-increasing number of aged people in our population, stem cells hold great potential for treating a number of age-related diseases and combating the disability and frailty that accompany the aging process. Developing therapies like these could potentially help older people to enjoy an improved level of physical performance and a better quality of life. Being able to remain mobile and independent as we grow older would be of huge benefit to not only the individual but also to families and society as a whole.

There are currently no FDA-approved treatments for age-related frailty, so this represents a huge unmet need that will only worsen with an increasingly aging population if those needs are not met by new medicines.

Seeing such tangible results in humans is a clear indication of the potential of rejuvenation biotechnology, and how we regard and treat aging will be changing in the near future.

Literature

[1] Nardi, N. B., & da Silva Meirelles, L. (2008). Mesenchymal stem cells: isolation, in vitro expansion and characterization. In Stem cells (pp. 249-282). Springer Berlin Heidelberg.

[2] Stolzing, A., Jones, E., McGonagle, D., & Scutt, A. (2008). Age-related changes in human bone marrow-derived mesenchymal stem cells: consequences for cell therapies. Mechanisms of ageing and development, 129(3), 163-173.

[3] Wang, S., Qu, X., & Zhao, R. C. (2012). Clinical applications of mesenchymal stem cells. Journal of hematology & oncology, 5(1), 19.

[4] Danielyan, L., Beer-Hammer, S., Stolzing, A., Schäfer, R., Siegel, G., Fabian, C., … & Novakovic, A. (2014). Intranasal delivery of bone marrow-derived mesenchymal stem cells, macrophages, and microglia to the brain in mouse models of Alzheimer’s and Parkinson’s disease. Cell transplantation, 23(1), S123-S139.

[5] Naaldijk, Y., Jaeger, C., Fabian, C., Leovsky, C., Blüher, A., Rudolph, L., … & Stolzing, A. (2017). Effect of systemic transplantation of bone marrow‐derived mesenchymal stem cells on neuropathology markers in APP/PS1 Alzheimer mice. Neuropathology and applied neurobiology, 43(4), 299-314.

[6] Golpanian, S., DiFede, D. L., Khan, A., Schulman, I. H., Landin, A. M., Tompkins, B. A., … & Levis-Dusseau, S. (2017). Allogeneic Human Mesenchymal Stem Cell Infusions for Aging Frailty. Journals of Gerontology Series A: Biomedical Sciences and Medical Sciences, glx056.

[7] Franceschi, C., Garagnani, P., Vitale, G., Capri, M., & Salvioli, S. (2017). Inflammaging and ‘Garb-aging’. Trends in Endocrinology & Metabolism, 28(3), 199-212.

[8] Tompkins, B. A., DiFede, D. L., Khan, A., Landin, A. M., Schulman, I. H., Pujol, M. V., … & Mushtaq, M. (2017). Allogeneic Mesenchymal Stem Cells Ameliorate Aging Frailty: A Phase II Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Journals of Gerontology Series A: Biomedical Sciences and Medical Sciences, 72(11), 1513-1522.

 

About Steve Hill

As a scientific writer and a devoted advocate of healthy longevity technologies, Steve has provided the community with multiple educational articles, interviews, and podcasts, helping the general public to better understand aging and the means to modify its dynamics. His materials can be found at H+ Magazine, Longevity Reporter, Psychology Today, and Singularity Weblog. He is a co-author of the book Aging Prevention for All – a guide for the general public exploring evidence-based means to extend healthy life (in press).

About LIFE EXTENSION ADVOCACY FOUNDATION (LEAF)

In 2014, the Life Extension Advocacy Foundation was established as a 501(c)(3) non-profit organization dedicated to promoting increased healthy human lifespan through fiscally sponsoring longevity research projects and raising awareness regarding the societal benefits of life extension. In 2015 they launched Lifespan.io, the first nonprofit crowdfunding platform focused on the biomedical research of aging.

They believe that this will enable the general public to influence the pace of research directly. To date they have successfully supported four research projects aimed at investigating different processes of aging and developing therapies to treat age-related diseases.

The LEAF team organizes educational events, takes part in different public and scientific conferences, and actively engages with the public on social media in order to help disseminate this crucial information. They initiate public dialogue aimed at regulatory improvement in the fields related to rejuvenation biotechnology.

I am the Lifespan – Video by Gennady Stolyarov II

I am the Lifespan – Video by Gennady Stolyarov II

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Gennady Stolyarov II


Gennady Stolyarov II, Chairman of the United States Transhumanist Party, discusses why longevity research is crucial, and how our generation stands on the threshold of finally dealing a decisive blow to the age-old enemies of aging and death, which have destroyed great human minds since the emergence of our species.

This video is part of the #IAmTheLifespan campaign, coordinated by Lifespan.io and the Life Extension Advocacy Foundation (LEAF) for Longevity Month, October 2017. Read more about this campaign here.

Become a member of the U.S. Transhumanist Party for free, no matter where you reside. Fill out our Membership Application Form here.

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