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SVAI Undiagnosed-1 Collaborative Genomics Research Case: A Call for Bioinformatics and/or Computational Biology Researchers to Get Involved

SVAI Undiagnosed-1 Collaborative Genomics Research Case: A Call for Bioinformatics and/or Computational Biology Researchers to Get Involved

SVAI


Editor’s Note: The U.S. Transhumanist Party / Transhuman Party provides this announcement to encourage any of our members and allies with expertise in bioinformatics and/or computational biology to contribute their talents to resolving the medical conundrum of one of our longtime loyal members, John – referred to in the Patient Case Background below as JCM – who has suffered from an undiagnosed condition his entire life. The Undiagnosed-1 Collaborative Genomics Research Case, arranged by the non-profit, volunteer-run organization SVAI, will take place on June 7-9 in San Francisco.  Find out more about this effort at breakthrough medical diagnosis – which could make a lifetime’s worth of difference to John – here. Even if you cannot attend the event in person, you can apply to participate in the research online here. John has generously provided for his data to be made available in an open-source manner so that future researchers into rare diseases could benefit from it and advance the state of medical science. Researchers have already agreed to study the data; one of them, longtime life-extension advocate Kevin Perrott, the CEO and Founder of OpenCures, a company located at the Buck Institute for Research on Aging that helps individuals performing self-directed research to access technologies and education, wishes to use mass spectrometry-based metabolomics and proteomics to find biomarkers of aging, and John has agreed to be a part of that project. John’s quest to discover the causes of his own ailment can thus lead to beneficial insights that could be used to research ways the extend the lifespans of all. The U.S. Transhumanist Party / Transhuman Party fully supports this noble effort and is heartened that many prominent researchers have already stepped forward to participate. However, there can never be enough trained and talented minds working on such endeavors, so, if you have the relevant expertise, we strongly encourage you to get involved.

~ Gennady Stolyarov II, Chairman, United States Transhumanist Party / Transhuman Party, May 21, 2019


PATIENT CASE BACKGROUND

  1. Our patient, JCM, is a 33-year-old Caucasian male suffering from undiagnosed disease(s).
  2. As an infant, the patient, JCM reports a history of vomiting after breastfeeding and Failure to Thrive (FTT).
  3. Since childhood, JCM has had a significant issue in weight gaining despite adequate caloric intake, though his height has remained on the curve. As a child, he also has reported nausea, stomach aches and an overall aversion to food.
  4. In his 20’s, JCM’s GI issues became more severe as he began to have daily lower abdominal pain characterized by burning and nausea. He began to develop chronic vomiting daily and would vomit as many as 5 times per day.
  5. At his current age, JCM is 5’10” tall and weighs 109lbs. He is easily fatigued due to his limited muscle mass and low weight.
  6. He reports several issues: pain and weakness in his knees, a couple of disc herniations, and shoulder dislocations. His GI issues and pain prevents him from attempts on building muscle masses with lifting and protein intake.

Learn more about the Undiagnosed-1 Collaborative Genomics Research Case here. You are encouraged to share this information with others who may be interested and qualified to assist.

 

Finally, Rejuvenation is a Thing! – Fresh Interview with Aubrey de Grey by Ariel VA Feinerman

Finally, Rejuvenation is a Thing! – Fresh Interview with Aubrey de Grey by Ariel VA Feinerman

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Ariel VA Feinerman
Aubrey de Grey


This interview was originally published here

Preface

What is ageing? We can define ageing as a process of accumulation of the damage which is just a side-effect of normal metabolism. While researchers still poorly understand how metabolic processes cause damage accumulation, and how accumulated damage causes pathology, the damage itself — the structural difference between old tissue and young tissue — is categorized and understood pretty well. By repairing damage and restoring the previous undamaged — young — state of an organism, we can really rejuvenate it! It sounds very promising, and so it is. And for some types of damage (for example, for senescent cells) it is already proved to work!

Today in our virtual studio, somewhere between cold, rainy Saint-Petersburg and warm, sunny Mountain View, we meet Aubrey de Grey, again! For those of you who are not familiar with him, here is a brief introduction.

Dr Aubrey de Grey is the biomedical gerontologist who researched the idea for and founded SENS Research Foundation. He received his BA in Computer Science and Ph.D. in Biology from the University of Cambridge in 1985 and 2000, respectively. Dr. de Grey is Editor-in-Chief of Rejuvenation Research, 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 organizations. In 2011, de Grey inherited roughly $16.5 million on the death of his mother. Of this he assigned $13 million to fund SENS research.

Note: If you have not read “Ending Aging” yet I suggest you to do it as soon as possible, and to be more comfortable with the ideas we are discussing below I highly recommend you to read short introduction to SENS research on their web page. Also if you are interested in recent news and up-to-date reviews about [anti]ageing and rejuvenation research the best place to look for is Fight Aging! blog. Finally, if you are an investor or just curious, I highly encourage you to take a look at Jim Mellon’s book “Juvenescence”.

Interview

Ariel Feinerman: Hello, Dr Aubrey de Grey!

Aubrey de Grey: Hello Ariel — thanks for the interview.

Ariel Feinerman: How do you feel 2018 year? Can you compare 2018 to 2017 or early years? What is changing?

Aubrey de Grey: 2018 was a fantastic year for rejuvenation biotechnology. The main thing that made it special was the explosive growth of the private-sector side of the field — the number of start-up companies, the number of investors, and the scale of investment. Two companies, AgeX Therapeutics and Unity Biotechnology, went public with nine-digit valuations, and a bunch of others are not far behind. Of course this has only been possible because of all the great progress that has been made in the actual science, but one can never predict when that slow, steady progress will reach “critical mass”.

Ariel Feinerman: In 2017 SENS RF have received about $7 million. What has been accomplished in 2018?

Aubrey de Grey: We received almost all of that money right around the end of 2017, in the form of four cryptocurrency donations of $1 million or more, totalling about $6.5 million. We of course realised that this was a one-off windfall, so we didn’t spend it all at once! The main things we have done are to start a major new project at Albert Einstein College of Medicine, focused on stem cell therapy for Alzheimer’s, and to broaden our education initiative to include more senior people. See our website and newsletters for details.

Ariel Feinerman: What breakthroughs of 2018 can you name as the most important by your choice?

Aubrey de Grey: On the science side, well, regarding our funded work I guess I would choose our progress in getting mitochondrial genes to work when relocated to the nucleus. We published a groundbreaking progress report at the end of 2016, but to be honest I was not at all sure that we would be able to build quickly on it. I’m delighted to say that my caution was misplaced, and that we’ve continued to make great advances. The details will be submitted for publication very soon.

Ariel Feinerman: You say that many of rejuvenating therapies will work in clinical trials within five years. Giving that many of them are already working in clinical trials or even in the clinic (like immunotherapiescell and gene therapies) do you mean the first — maybe incomplete — rejuvenation panel, when you speak of early 2020?

Aubrey de Grey: Yes, basically. SENS is a divide-and-conquer approach, so we can view it in three overlapping phases. The first phase is to get the basic concept accepted and moving. The second phase is to get the most challenging components moving. And the third phase is to combine the components. Phase 1 is pretty much done, as you say. Phase 2 is beginning, but it’s at an early stage. Phase 3 will probably not even properly begin for a few more years. That’s why I still think we only have about a 50% chance of getting to longevity escape velocity by 2035 or so.

Ariel Feinerman: Even now many investors are fearful of real regenerative medicine approaches. For example pharmacological companies which use small molecules, like Unity Biotechnology, received more than $300 million, in much more favour than real bioengineering companies like Oisin Biotechnologies, received less than $4 million, even though the biological approach is much more powerful, cheap, effective and safe! Why is this so in your opinion, and when can we see the shift?

Aubrey de Grey: I don’t see a problem there. The big change in mindset that was needed has already occurred: rejuvenation is a thing. It’s natural that small-molecule approaches to rejuvenation will lead the way, because that’s what pharma already knows how to do. Often, that approach will in due course be overtaken by more sophisticated approaches. Sometimes the small molecules will actually work well! It’s all good.

Ariel Feinerman: Do you agree that the small-molecule approach is generally the wrong way in the future rejuvenation therapies? Because they have many flaws — especially their main mechanism via interference with human metabolism. Unlike them SENS bioengineering therapies are designed to be metabolically inert — because they just eliminate the key damage, they do not need to interfere with metabolism, so it is much easier than usual to avoid side effects and interactions with other therapies. They just eliminate the key damage, which means they are easier to develop and test — and much safer.

Aubrey de Grey: Ah, no, that’s too simplistic. It’s not true that small molecules always just “mess with metabolism” whereas genetic and enzymatic approaches eliminate damage. Small molecules that selectively kill senescent cells are absolutely an example of SENS-esque damage repair; the only thing against them is that it may be more difficult to eliminate side-effects, but that’s not because of their mode of action, it’s because of an additional action.

Ariel Feinerman: In recent years many countries gave the green light for regenerative medicine. Fast-track approval in Japan, for example, allows for emerging treatments to be used so long as they have been proven safe. The similar approach works in Russia. What about the EU or USA?

Aubrey de Grey: There’s definitely a long way to go, but the regulatory situation in the West is moving in the right direction. The TAME trial has led the way in articulating an approvable endpoint for clinical trials that is ageing in all but name, and the WHO has found a very well-judged way to incorporate ageing into its classification.

Ariel Feinerman: Do you think of working with USA Army? As far as we know they conduct research on regeneration and are very interested in keeping soldiers healthier for longer. And they have much money!

Aubrey de Grey: The Department of Defense in the USA has certainly funded a lot of high-impact regenerative medicine research for many years. I’m sure they will continue to do so.

Ariel Feinerman: Is any progress in the OncoSENS programme? Have you found any ALT genes? Is any ongoing research in WILT?

Aubrey de Grey: No — in the end that program was not successful enough to continue with, so we stopped it. There is now more interest in ALT in other labs than there was, though, so I’m hopeful that progress will be made. But also, one reason why I felt that it was OK to stop was that cancer immunotherapy is doing so well now. I think there is a significant chance that we won’t need WILT after all, because we will really truly defeat cancer using the immune system.

Ariel Feinerman: Spiegel Lab has recently published an abstract where they say they have found 3 enzymes capable of breaking glucosepane. Very exiting info! When can we hear more on their research? Revel LLC is a very secretive company.

Aubrey de Grey: They aren’t really being secretive, they are just setting up.

Ariel Feinerman: When can we see the first clinical trial of glucosepane breaker therapy?

Aubrey de Grey: I think two years is a reasonable estimate, but that’s a guess.

Ariel Feinerman: What do you think of the Open Source approach in rejuvenation biotechnology? The computer revolution in the early 2000s has taken place only because Open Source caused an explosion in software engineering!

We have many examples when Big Pharma buys a small company which has patents on technology and then cancels all research. In the Open Source approach you cannot “close” any technology, while everyone can contribute, making protocol better and everyone can use that without any licence fee! Anyway, there are countries where you cannot protect your patents. Maybe it will be better to make technology open from the beginning?

Famous biohacker Josiah Zayner said: “In the gene therapy world most treatments are easy to replicate or pirate because you can reverse engineer the DNA from scientific papers or patents. Same exact treatment, same purity and quality I could give to someone rejected from the clinical trial. The cost? Hundreds or a few thousand dollars at most. Same deal with immunotherapy.”

Aubrey de Grey: I think you’ve pretty much answered your own question with that quote. The technologies that will drive rejuvenation are not so easy to suppress.

Ariel Feinerman: Is the SENS RF going to begin new research programmes in 2019?

Aubrey de Grey: Sure! But we are still deciding which ones. We expect that our conference in Berlin (Undoing Aging, March 28–30) will bring some new opportunities to our attention.

Ariel Feinerman: What are your plans for 2019?

Aubrey de Grey: I’d like to say less travelling, but that doesn’t seem very likely at this point. Really my goal is just to keep on keeping on — to do all I can to maintain the growth of the field and the emerging industry.

Ariel Feinerman: Thank you very much for your answers, hope to see you again!

Aubrey de Grey: My pleasure!

Ariel VA Feinerman is a researcher, author, and photographer, who believes that people should not die from diseases and ageing, and whose main goal is to improve human health and achieve immortality. If you like Ariel’s work, any help would be appreciated via PayPal: arielfeinerman@gmail.com.

2019 New Year’s Message – A Call for Medical Progress and Preservation of the Good – Article by Victor Bjoerk

2019 New Year’s Message – A Call for Medical Progress and Preservation of the Good – Article by Victor Bjoerk

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Victor Bjoerk


I celebrated the end of 2018 like normally with neuroscientist Anders Sandberg and several other “transhumanists” or “technoprogressive people” in Stockholm!

Why am I in that place to start with? Well, I’m quite frustrated with the human condition in the first place; I’ve always questioned everything from social norms and different kinds of problems in the world, and there’s still so much misery around that we need to unite and fix. (I know it sounds cliché, but it’s true!)

As people reading this know, the vast majority of human misery worldwide today occurs due to our bodies damaging themselves with the passage of time, the biological process we call aging. This occurs because evolution has no goals and our ancestors died at the age of 30-40 prehistorically, and therefore there was no pressure for evolution to create humans that could repair themselves molecularly to live thousands of years. The closest we get among Eukaryotes/Vertebrates are Greenland sharks, which can live to 500+ years; that is easy to understand since they have no predators and just have to open their mouths to get their daily food. On the opposite side we have as a prominent example the mouse, with a very poor molecular repair system and subsequent 2.5-year lifespan, easy to understand when you realize how dangerous life is in the wild if having a mouse body.

Thanks to our technology, we have created the “paradise Greenland shark scenario” for humans during the past century essentially, creating very comfortable existences where nearly everyone survives.

So if you’re 25 years old, life is really great nowadays in Western countries (unless you like to complain about everything!); the existential risks are so low in the absence of aging that you would live many thousands of years just by being a young person living in Sweden.

So I’ve worked a lot in nursing homes both before and during my studies in molecular biology, and what those people have to endure would be strictly illegal in most countries if we knew how to change it. Imagine if, for example, Saudi Arabia allowed its citizens to age while the Western world had abolished it; wouldn’t Amnesty International intervene?

But what can be done with the human body? Well, I assume quite a lot! We are seeing so many people who can’t stand the medical monopoly and the 17-year bench-to-bedside status quo, which isn’t an abstract academic complaint but which impact their daily lives, so they start self-experimenting with, for example, senolytic medicines to kill their senescent cells, making themselves “younger” in certain aspects, which is pretty cool!

However I’m not someone who constantly calls for change and “progress”; I mean, if something is nice, then why not keep it? As far as I’m concerned, for example, the beautiful architecture from the past can continue to stand for thousands more years. These buildings fulfill their purpose and look nice; I’m quite conservative on those points – but please accelerate the medical research, and it is crucial to spot the techniques that actually do work and to not waste resources on hype!

2018 has brought me many good things, those which one can call “achievements” and those which are not visible. The Eurosymposium on Healthy Aging in Brussels became a success! (And there will be some events during 2019 that I am also announcing for everyone who enjoyed it!)

I’ve been learning a lot about CRISPR and many other techniques both practically and theoretically, though I have not exactly used them to change the world. Medical progress takes forever to achieve, and it’s not exactly helped by a massive web of bureaucracy/hierarchies/prestige/laws, all contributing to slowing down progress for people in need. What can really be done? One needs to focus on the positive and go where the biotech companies can succeed!

So if things are working out for me as I hope now in 2019, I hope being able to really work full time to impact the longevity industry, I really feel like an overripe fruit that needs to get things done, because implementing stuff is what matters and not becoming some passive “longevity encyclopedia”. I’ll keep everyone as usually updated!

So happy new 2019 everyone! And make sure to take good care of yourselves!

Victor Bjoerk has worked for the Gerontology Research Group, the Longevity Reporter, and the Fraunhofer-Institut für Zelltherapie und Immunologie. He has promoted awareness throughout Europe of emerging biomedical research and the efforts to reverse biological aging. 

Boosting Bone Healing Using a Key Protein – Article by Steve Hill

Boosting Bone Healing Using a Key Protein – Article by Steve Hill

Steve Hill


Editor’s Note: In this article, Mr. Steve Hill highlights research on selective bone regeneration using a protein called Jagged-1. This article was originally published by the Life Extension Advocacy Foundation (LEAF).

                   ~ Kenneth Alum, Director of  Publication, U.S. Transhumanist Party, March 7, 2018

Today, we would like to highlight a recent study in which researchers show a way to selectively accelerate bone regeneration. They have achieved this by delivering Jagged-1 to injuries instead of the bone morphogenetic proteins (BMPs) that have been traditionally used.

What is Jagged-1?

Jagged-1 is an osteoinductive protein that activates the Notch signaling pathway, which regulates bone healing at the site of injury. Osteoinduction is the process by which osteogenesis is induced.

Osteoinduction involves recruiting immature cells and stimulating them to change into preosteoblasts. In a bone healing situation, such as during a fracture, the majority of bone healing depends on osteoinduction.

The new technique avoids the issues of inappropriate or excessive bone growth because, unlike BMPs, it targets osteoinductive mechanisms that are more directly associated with the regenerative process.

Testing their hypothesis

The researchers led by Kurt Hankenson, D.V.M., Ph.D., a professor of orthopedic surgery at Michigan Medicine, hypothesized for some years that by binding Jagged-1 to a biomaterial structure and delivering it to the site of injury, it could improve healing of the bone.

The published study results confirm this to be the case [1]. Mice and rats that were given Jagged-1, applied using a wet collagen sponge, saw improvements to both femoral and skull injuries. In contrast, the rodents treated with BMPs benefited but also experienced problematic bone hypertrophy, which is also observed in humans using BMPs.

The findings of this study suggest that the use of Jagged-1 for location-specific bone injury could potentially be developed into a therapy to help people recover from fractures and broken bones.

Conclusion

The use of signal molecules rather than drugs to encourage tissue regeneration is likely to increase in popularity in the coming years as the process becomes increasingly refined. This study is yet another example of how researchers are exploring the use of signalling molecules produced naturally in the body as an alternative to drug approaches, which can often have unwanted side effects. It should prove interesting to see how this approach develops in the next few years.

Literature

[1] Youngstrom, D. W., Senos, R., Zondervan, R. L., Brodeur, J. D., Lints, A. R., Young, D. R., … & Loomes, K. M. (2017). Intraoperative delivery of the Notch ligand Jagged-1 regenerates appendicular and craniofacial bone defects. NPJ Regenerative medicine, 2(1), 32.

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.

Dentists May Soon Regenerate Teeth Using GSK3 Antagonists – Article by Steve Hill

Dentists May Soon Regenerate Teeth Using GSK3 Antagonists – Article by Steve Hill

Steve Hill


Editor’s Note: In this article, Mr. Steve Hill explains a teeth-regeneration technique that works by activating the stem cells that reside in the dental pulp of teeth. The technique has the potential to translate to other tissues to help encourage regeneration. This article was originally published by the Life Extension Advocacy Foundation (LEAF).

                   ~ Kenneth Alum, Director of  Publication, U.S. Transhumanist Party, March 6, 2018

What if I told you that we could regenerate our teeth? Well, that may soon be a possibility thanks to new research showing that teeth can be encouraged to regrow. Rather than drilling holes into teeth and plugging them with artificial fillers, dentists in the near future may be able to rebuild your teeth with a new technique.

Stimulating stem cells

Professor Paul Sharpe, a scientist based at King’s College in London, and his team have found a way to do just this in mice. They published a study last year that described this new approach [1].

The researchers wanted to increase the natural ability of teeth to repair themselves by activating the stem cells that reside in the dental pulp of teeth. They knew that previous research showed that the wnt signaling pathway is a key pathway for stem cell activity in many parts of the body, and they wanted to see if it works the same way in teeth.

The researchers believed by that using drugs to stimulate the wnt pathway, they could increase stem cell activity in teeth and boost their regenerative potential significantly. Normally, this level of regeneration is only seen in animals like starfish and salamanders, but the researchers wanted to see if we can benefit from the same regenerative capacity.

To see if this would work, the team drilled holes into the molar teeth of mice to simulate dental cavities. Next, they exposed collagen sponges (the same protein found in the dentin in teeth) to a variety of drugs known to stimulate the wnt pathway. Then, they placed these sponges into the cavities and sealed them in for between 4 to 6 weeks.

After this time, the researchers saw that the teeth exposed to these sponges had created a lot more dentin than the control mice and mice given typical dental fillers. The researchers observed that this was essentially a full repair and, in most cases, the teeth of the mice were as good as new.

The next step towards clinical trials

Since then, the researchers have tested the technique on rats, which have considerably larger teeth than mice, making them the logical next step. The research team report that the therapy worked equally well on the rats as it did in the mice in the original study; however, the data is yet to be published.

The researchers are now screening their drug candidates to identify the most effective of the wnt-stimulating drugs. They are also adapting the technique to work with modern dental practices by injecting a gel containing the drug into a dental cavity and hardening it using a UV light to seal it in. This is similar to how dentists currently seal and repair teeth, so this technique would be easy to incorporate into dental practice.

Literature

It will be several years before this enters human clinical trials, but the results so far are promising, and the process may be quicker than normal because a number of the candidate drugs are already approved for human use. The arrival of this technique will revolutionize dentistry and is a great step forward for regenerative medicine in general.

Such techniques have the potential to translate to other tissues to help encourage regeneration, so it is also relevant to aging research. We look forward to more developments from this team in the future.

References

[1] Neves, V. C., Babb, R., Chandrasekaran, D., & Sharpe, P. T. (2017). Promotion of natural tooth repair by small molecule GSK3 antagonists. Scientific reports, 7, 39654.

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.

Exosome Therapy Repairs Stroke-Damaged Brain Tissue – Article by Steve Hill

Exosome Therapy Repairs Stroke-Damaged Brain Tissue – Article by Steve Hill

Steve Hill


Editor’s Note: In this article, Mr. Steve Hill explains a new therapy that uses exosomes to repair damaged brain cells. The human trials are intended to begin in the year 2019. This article was originally published by the Life Extension Advocacy Foundation (LEAF).

                   ~ Kenneth Alum, Director of  Publication, U.S. Transhumanist Party, March 5, 2018

Today, we wanted to highlight more progress in a rapidly advancing area of medicine and talk about a new study that uses an exosomes-based approach for stroke treatment that repairs brain tissue.

A stem cell-based approach to treating stroke

Professor Steven Stice from the University of Georgia (UGA) and Nasrul Hoda of Augusta University led the team that developed AB126, a treatment that uses a type of extracellular vesicle known as an exosome [1]. Exosomes are small fluid-filled structures that are created by stem cells and, in the case of AB126, are produced by human neural stem cells.

Essentially, the researchers are isolating the beneficial signals given out by stem cells and using them rather than the stem cells as a therapy. This makes sense, as other cells react to these signals and change their behavior accordingly. We have talked about the therapeutic potential of extracellular vesicles, particularly exosomes, in a previous article.

An exosome can remain hidden in the bloodstream, carry multiple doses, and store and administer treatment, and its small size allows it to cross barriers that cells cannot. This is ideal for delivering therapies to the brain, as it crosses the blood-brain barrier and other checkpoints in the body.

After the administration of AB126,  the researchers used MRI scans to assess brain atrophy rates in an animal model of stroke. The scans showed around 35 percent decrease in the size of injury and a 50 percent reduction in brain tissue loss. These results were also replicated by Franklin West, associate professor of animal and dairy science at UGA, in a pig model of stroke.

Within days, the researchers observed improved mobility, better balance, and measurable behavioral benefits in treated animal models of stroke.

Based on the successful results of these preclinical tests, the next step is to take this therapy to human clinical trials by 2019 via ArunA Biomedical, a UGA startup company. The company plans to expand its scope beyond stroke, and preclinical studies in epilepsy, traumatic brain, and spinal cord injuries begin later this year.

Conclusion

This is another example of the recent interest in using extracellular vesicles, such as exosomes, as therapies rather than stem cells themselves. Multiple research groups are now developing these therapies to treat various age-related diseases, so we can almost certainly expect to hear more in the near future.

The use of extracellular vesicles also holds the promise of being more cost-effective from the point of view of storage, logistics, manufacture, and delivery. With the first clinical trials now in the cards for the near future, it will be interesting to see how this develops in the next few years.

References

[1] Webb, R. L., Kaiser, E. E., Scoville, S. L., Thompson, T. A., Fatima, S., Pandya, C., … & Baban, B. (2017). Human Neural Stem Cell Extracellular Vesicles Improve Tissue and Functional Recovery in the Murine Thromboembolic Stroke Model. Translational stroke research, 1-10.

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.

Gene Cocktail Helps Hearts to Regenerate – Article by Steve Hill

Gene Cocktail Helps Hearts to Regenerate – Article by Steve Hill

Steve Hill


Editor’s Note: In this article, Steve Hill explains a technique that enables significant human tissue regeneration, so that it becomes possible to repair damaged human hearts. This technique can also be potentially applied to other body organs.  This article was originally published by the Life Extension Advocacy Foundation (LEAF).

                   ~ Kenneth Alum, Director of  Publication, U.S. Transhumanist Party, March 4, 2018

The human heart is an organ whose cells rarely divide, making tissue repair and regeneration a huge problem following a heart attack. Many animals, such as zebrafish and salamanders, are different; they can regenerate damaged hearts easily.

As humans, we also once had the same regenerative capacity during our early development, but after we were born, we lost this ability. This is also true for many other organs, including the brain, spinal cord, and pancreas. The cells in these tissues divide very rarely if at all, and this is a big problem. But, what if we could get that regenerative ability back and repair damage to our hearts the way these amazing animals do?

Researchers have been trying for decades to find out how we can enjoy the same tissue regeneration, but they have met with limited success—until now.

Unlocking cell division in cardiomyocytes

A research team led by Dr. Deepak Srivastava, president of the Gladstone Institutes, has finally achieved this long sought-after goal in a study published in the journal Cell [1]. The researchers have developed an efficient and reliable way of making non-dividing adult cardiomyocytes divide so that they can repair damaged hearts.

They identified four genes that regulate cell division in adult cardiomyocytes. When all four of them are combined together, they cause the cardiomyocytes to re-enter the cell cycle and start dividing quickly. They also demonstrated that following heart failure, these combined genes improve cardiac function significantly.

The researchers tested the technique in animal models using cardiomyocytes derived from human stem cells. They stained newly divided cells with a special dye in order to track them; they found that between 15 to 20 percent of the cells divided and remained alive thanks to the four-gene combo. This is a vast improvement on previous studies, which have only managed around 1 percent cell division in adult cardiomyocytes.

The team also made the technique simpler by identifying drugs that could replace two of the four genes involved in the combination. This still produced the same result as using all four genes and is significantly easier, logistically speaking.

Could be used in multiple tissues

As mentioned, the heart is not the only tissue that has cells that either do not divide or do so very slowly. The researchers believe that their technique could also potentially be applied to encourage other tissues and organs to regenerate. This is because the four genes are not unique to the heart and are found in other cells around the body.

If science can unlock the same regeneration in nerve cells, pancreatic cells, and retinal cells, this could be the basis of therapies for heart failure, brain damage, diabetes, blindness, and many other conditions. The good news is these four genes encourage cell division the same way in mice, rats, and human cells.

Conclusion

Manipulating non-dividing cells and returning them to the cell cycle to boost regeneration in organs and tissues holds great potential. Scientists have been working for decades to achieve this in the heart, and now it has been achieved. The next big step is to translate this approach to humans, and we wish them the very best in their future research.

Literature

[1] Mohamed, T. M., Ang, Y. S., Radzinsky, E., Zhou, P., Huang, Y., Elfenbein, A., … & Srivastava, D. (2017). Regulation of Cell Cycle to Stimulate Adult Cardiomyocyte Proliferation and Cardiac Regeneration.

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.

Google’s Calico Labs Announces Discovery of a “Non-Aging Mammal” – Article by Brady Hartman

Google’s Calico Labs Announces Discovery of a “Non-Aging Mammal” – Article by Brady Hartman

Brady Hartman


Editor’s Note: In this article, Mr. Brady Hartman explains a study that shows the naked mole-rats have an extremely low rate of aging.  This article was originally published by the Life Extension Advocacy Foundation (LEAF).

                   ~ Kenneth Alum, Director of  Publication, U.S. Transhumanist Party, February 19, 2018

Completely bald and with wrinkly skin, the naked mole rat is one of the ugliest creatures around but lives an exceptionally long life for a small mammal. It rarely develops the chronic diseases of aging, such as cancer, and lives 10 times longer than regular rats.

The First Non-Aging Mammal

In the first significant announcement from Calico Labs since it was formed in 2013, researchers Rochelle Buffenstein, Megan Smith, and J. Graham Ruby have announced that the naked mole rat is a “non-aging mammal.”

The researchers followed the naked mole rats – housed at the Buck Institute – over a three-decade-long study period. They found that these creatures show hardly any signs of aging, such as problems with their metabolism, heart, or bones. Females do not go through menopause and continue to reproduce into their 30s, which is an amazing feat for an animal that lives at least 30 years of age in captivity. Even the cells in their bodies have a remarkable resistance to oxidative damage caused by free radicals. Small rodents the size of the naked mole rat live for no more than six years.

Senior Principal Investigator Rochelle (Shelley) Buffenstein, Ph.D. spent the early part of her career at the Medical School of the University of Witwatersrand, South Africa, where she studied the naked mole rat for ten years. Principal Investigator J. Graham Ruby, Ph.D. received his doctorate in biology from MIT and performs biometric, biostatistical, bioinformatic, and quantitative genetic analyses of diverse data to decipher the aging process in humans and model organisms. The researchers published their results on Jan 24th in the open access journal eLife [1].

How the Non-Aging Mammal Was Discovered

To judge the rate of aging, the Calico team used a mathematical model called the Gompertz-Makeham law of mortality. This statistically validated law states that the risk of death for every mammal increases exponentially with increasing age. The Calico researchers used this model to analyze an existing data set of more than 3000 naked mole rats over a 30-year timespan and found that the small mammals did not conform to the Gompertz-Makeham law. Unlike every other mammal, the mole rats do not face an increased hazard of death with each birthday; as the Calico authors said, “This absence of hazard increase with age, in defiance of Gompertz’s law, uniquely identifies the naked mole-rat as a non-aging mammal.”

Estimated probability of a US person dying at each age (2003.) Credit: Uscitizenjason CC BY SA 3.0

This is astonishing given that all other mammals, including humans, face an increased rate of death with each passing birthday. Consider this hazard chart for US citizens in 2003, in which the mortality rates increase exponentially with age after the age of 30.  In contrast, the equivalent chart for the naked mole rat is almost flat.

Caleb E. Finch and Hiram Beltrán-Sánchez, a pair of scientists from the University of Southern California (USC) in Los Angeles, analyzed and commented on the study. Caleb E. Finch, Ph.D. is a molecular biologist in the Leonard Davis School of Gerontology and Dornsife College. Hiram Beltrán-Sánchez is from the Department of Community Health Sciences and the California Center for Population Research.

Commenting on the remarkable results of the study in a companion piece [2], Finch and Beltrán-Sánchez said that the naked mole rat defied the Gompertz-Makeham law, remarking, “their risk of death does not increase as they get older” and “this is unprecedented for mammals.”

Finch and Beltrán-Sánchez said that previous studies of the non-aging mammal suggest that aging creeps in, nevertheless. Naked mole rats can accumulate oxidative damage in their cells and experience muscle wasting. There is also some evidence for small amounts of cancer. But, after reviewing the evidence, the USC authors said, “This would suggest that unlike any other mammal, the naked mole rats have an extremely low rate of aging.”

Finch and Beltrán-Sánchez said that the minimal age-related problems of the mole rat combined with its long lifespan allow it to achieve ‘negligible senescence,’ a phenomenon in which an animal reaches an advanced age without increased mortality or disability.

Other scientists believe that the longevity of naked mole rats is due to the limited oxygen of their subterranean habitat. Because of this environment, their metabolic rates are abnormally slow, and an abundance of repair mechanisms keeps their cells astonishingly youthful.

About Longevityfacts

LEAF has teamed up with its friends at LongevityFacts and will be publishing some of their articles as part of an agreed syndication deal. This article originally appeared here at LongevityFacts.

References

[1] J Graham Ruby, Megan Smith, Rochelle Buffenstein, Calico Life Sciences LLC. “Naked mole-rat mortality rates defy Gompertzian laws by not increasing with age.” eLife 2018;7:e31157 DOI: 10.7554/eLife.31157, Jan 24, 2018.

[2] Hiram Beltrán-Sánchez, Caleb Finch. “Life Expectancy: Age is just a number.” eLife 2018;7:e34427 DOI: 10.7554/eLife.34427 Jan 24, 2018.

 

About Brady Hartman

Brady is the editor of the longevity focused blog LongevityFacts.com and is an active advocate for rejuvenation biotechnology and geroscience.

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.

Is Aging Natural, a Disease That We Can Treat, or Both? – Article by Steve Hill

Is Aging Natural, a Disease That We Can Treat, or Both? – Article by Steve Hill

Steve Hill


Editor’s Note: In this article, Mr. Steve Hill explains that aging can be described as both natural and pathological without contradiction. This article was originally published by the Life Extension Advocacy Foundation (LEAF).

                   ~ Kenneth Alum, Director of  Publication, U.S. Transhumanist Party, February 16, 2018

Aging is something that we all share, rich or poor; it is something that happens to us all, and we are taught from a young age that it is inevitable. However, some scientists believe that aging is amenable to medical intervention and that such interventions could be the solution to preventing or reversing age-related diseases.

Academics are currently debating whether aging is natural or a pathological disease that we can treat.

In fact, there is now pressure from many academics to classify aging itself as a disease; indeed, doing so could potentially improve funding for aging research and help to speed up progress in finding solutions to age-related diseases. [1] The debate continues, but does it really matter if aging is classified as a disease, or is it largely a matter of semantics?

Fighting a losing battle

Current medical practice sees us trying to treat age-related diseases in the same way we do other diseases; this is the “infectious disease model”, and when it comes to treating age-related diseases, it is a losing battle.

The current approach works like this: as soon as a disease appears, the doctor attacks the disease using everything in the medical armory, and the patient can then continue with life until the next disease happens; this process is repeated until failure. This is an excellent way to deal with infectious diseases, and it has helped to increase life expectancy greatly in the last century; however, there are signs are that this approach is starting to run out of steam. [2-4]

Unfortunately, this “whack-a-mole” approach is a poor choice when it comes to treating the chronic diseases of old age. This is because the damage that the aging processes cause still continues to take its toll; therefore, treating the symptoms will ultimately achieve very little and certainly not cure the disease.

So, given that the aging processes lead to the diseases of aging, it is understandable that scientists are starting to consider aging itself to be a disease. While we do not yet fully understand all the intricacies of aging, we already know a great deal about the individual processes.[5] Certainly, we now know enough about aging to begin developing and testing interventions that directly target the underlying processes in order to prevent or treat pathology.

Treating the underlying processes and repairing their damage, which leads to the familiar diseases of old age, is the basis for the medical approach known as rejuvenation biotechnology, a multidisciplinary field that aims to prevent and treat age-related diseases by targeting the aging processes directly.

Aging is the foundation of age-related diseases

Even if aging is not a disease itself, the individual processes do lead to pathology and age-related diseases, such as cancer, heart disease, Parkinson’s, and Alzheimer’s. So, knowing that these processes create the conditions for diseases to develop, it makes sense to target the processes themselves in order to potentially prevent or treat a slew of age-related diseases at once.

The changes that aging brings vary from one person to another, but the common processes of aging are at work in all of us, albeit with some small variances between individuals. For example, we all suffer wear and tear in our joints due to the loss of cartilage, and we all experience the loss of skin elasticity due to the degradation of elastin and the failure of connective tissues. We all encounter other age-related changes, such as the accumulation of non-dividing senescent cells that cause chronic inflammation and disrupt tissue repair, and we also suffer from the accumulation of metabolic waste products that collect in our bodies over time.

As these changes progress, they eventually lead to the familiar diseases of aging. For example, lipids are critical for the function of our metabolism and are essential as part of our diet; however, over time, these processed lipids begin to accumulate in the blood vessel walls. Macrophages arrive to clear the toxic fatty waste away, but they become immobilized and die. This causes inflammation, attracting more macrophages and continuing the cycle. Ultimately, this debris forms plaques that harden the blood vessels and cause them to narrow; this causes blood pressure to rise and can eventually result in a heart attack or stroke.

This demonstrates that the normal metabolic processes that keep us alive ultimately lead to disease. Importantly, in this case, the early age-related changes that set the scene for disease progression, such as high cholesterol, have no symptoms. Nevertheless, such changes are the precursors of deadly diseases and are considered suitable targets for treatment. The same can be said for the other, more subtle, changes and damages that the aging processes cause.

Age-related conditions, such as arthritis, diabetes, osteoporosis, Alzheimer’s, Parkinson’s and many cancers, all follow this dynamic. Simply put, given the sufficient passage of time, the aging processes will cause us to suffer from multiple diseases. Therefore, we should consider these diseases to be the clinical manifestation of these age-related changes. In fact, medicine has been fighting against age-related changes for a long time, even if it was not obvious. For example, a doctor recommending that his patient should reduce his fat and carbohydrate intake to delay heart disease is already fighting those age-related changes. The diabetic who modifies her diet to better manage blood sugar levels is also doing the same thing.

Some people might contest this point of view, stating that the aging process is “natural” and therefore cannot be a disease. The argument that natural things are always good, the appeal to nature, is a logical fallacy. Such people may see natural and pathological as being mutually exclusive. Thus, what is natural must always be good, and what is pathological is bad, and so it cannot also be natural. This is, of course, false when you consider the meaning of each word. Natural simply means something that follows the normal, established course of events, and pathological means something that is harmful.

Conclusion

So, is aging natural or pathological? Well, by the dictionary definitions, aging can be described as both natural and pathological without contradiction.

Additionally, as it is currently classified, aging could be considered a syndrome, specifically a co-morbid syndrome. This really does describe aging perfectly; it is a group of symptoms that consistently occur together and a condition characterized by a set of associated symptoms. Ultimately, aging is an umbrella term describing a range of pathological changes; it may struggle to be accepted as a disease, but it already qualifies as a syndrome.

However, the question of aging being a disease or not is essentially semantic in nature. What rejuvenation biotechnology seeks to achieve is nothing more than preventing age-related diseases by treating the early stages of pathology, which are considered a natural process. While these early age-related changes have not been given a disease name, they are instrumental in the development of diseases, and surely, when it comes to medical treatment, that is all that matters.

References

[1] Bulterijs, S., Hull, R. S., Björk, V. C., & Roy, A. G. (2015). It is time to classify biological aging as a disease. Frontiers in genetics, 6.

[2] Crimmins, E. M. (2015). Lifespan and healthspan: Past, present, and promise. The Gerontologist, 55(6), 901-911.

[3] Olshansky, S. J., Passaro, D. J., Hershow, R. C., Layden, J., Carnes, B. A., Brody, J., … & Ludwig, D. S. (2005). A potential decline in life expectancy in the United States in the 21st century. New England Journal of Medicine, 352(11), 1138-1145.

[4] Reither, E. N., Olshansky, S. J., & Yang, Y. (2011). New forecasting methodology indicates more disease and earlier mortality ahead for today’s younger Americans. Health Affairs, 10-1377.

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

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.

Could Filtering Our Aged Blood Keep us Young? – Article by Steve Hill and Nicola Bagalà

Could Filtering Our Aged Blood Keep us Young? – Article by Steve Hill and Nicola Bagalà

Steve Hill

Nicola Bagalà


Editor’s Note: In this article, Mr. Nicola Bagalà and Steve Hill present the interview they conducted with Dr. Irina Conboy of Berkeley University and Dr. Michael Conboy of Havard University on the topic of youthful blood.  This article was originally published by the Life Extension Advocacy Foundation (LEAF).

                   ~ Kenneth Alum, Director of  Publication, U.S. Transhumanist Party, February 17, 2018

Due to a recently published study on the effects of young plasma on aged mice, we got in touch with Dr. Irina Conboy of Berkeley University. Dr. Conboy is an Associate Professor at the Department of Bioengineering and an expert in stem cell niche engineering, tissue repair, stem cell aging and rejuvenation. Before we dive into the main topic, let’s familiarize ourselves a little with Dr. Conboy and her work.

Dr. Conboy got her Ph.D. at Stanford University, focusing on autoimmunity. She met her partner in science—and in life—Dr. Michael Conboy at Harvard and they got married before embarking on graduate studies; they celebrated their Silver Anniversary a few years ago. During her postdoctoral studies, she began focusing on muscle stem cells, trying to figure out what directs them to make new healthy tissue and what causes them to lose their ability to regenerate the tissues they reside in as we age [1].

Together with her husband Michael, she eventually discovered that old stem cells could be reactivated and made to behave like young ones if appropriately stimulated. The Conboys’ parabiosis experiments—which consisted in hooking up the circulatory systems of aged and young mice—showed that old age is not set in stone and can be reversed in a matter of weeks [2].

The follow-up work by the Conboys uncovered that age-accumulated proteins, such as TGF-β1, inhibited stem cells’ ability to repair tissues even in young mice, and when TGF-β1 signaling is normalized to its young levels, old mice (equivalent to 80-year old people) have youthful muscle regeneration and better neurogenesis in the hippocampus (the area of the brain that is responsible for memory and learning) [3].

While young blood did appear to be beneficial to old stem cells, their evidence suggested that the real culprit of the broad loss of tissue repair with age was the negative influence of age-accumulated inhibitory proteins in aged tissues and circulation, also called the stem cell niche [4].

This conclusion is certainly compatible with the view of aging as a damage accumulation process [5]. As Irina herself pointed out in this interview, in the parabiosis experiments, the old mice had access to the more efficient young organs: lungs, liver, kidneys and immune system of the younger mice, which likely accounted for many of the benefits observed in the elderly parabiosed mice. With respect to the rejuvenation of the brain, the old mice experienced environmental enrichment by being sutured to young, more active parabionts, and this is known to improve the formation of new brain cells, learning, and memory.

An aged niche blocks the action of old and young stem cells alike very quickly; therefore, as Dr. Conboy observed in an article in the Journal of Cell Biology, we can’t treat the diseases of aging by simply transplanting more stem cells, because they will just stop working. Their niche needs to be appropriately engineered as well. Fortunately, there are potential solutions to this problem; such as the use of artificial gel niches and defined pharmacology that are designed to protect transplanted or endogenous stem cells from the deleterious environment of the old body.

This research holds the potential to significantly postpone the onset of age-related diseases and possibly reverse them one day, including frailty, muscle wasting, cognitive decline, liver adiposity and metabolic failure, but Dr. Conboy remains cautious about the possibilities until more data is in. However, she does think that longer and healthier productive lives could improve people’s attitudes towards the environment and treating each other with compassion and respect—a view that we definitely share.

We managed to catch up with Irina and Michael Conboy and talk to them about their work.

For the sake of those new to the topic, what is it in young blood and aged blood that affects aging?

Irina: Numerous changes in the levels of proteins that together regulate cell and tissue metabolism throughout the body.

Mike: We wondered why almost every tissue and organ in the body age together and at a similar rate, and from the parabiosis and blood exchange work now think that young blood has several positive factors, and old blood accumulates several negative, “pro-aging” factors.

A lot of media attention and funding is currently being directed to youthful blood transfusions; how can we move beyond this to potentially more promising approaches, such as filtering and calibration of aged blood?

Irina: People need to understand not just the titles, abstracts and popular highlights of research papers, but the results and whether they support (or not) the promise of rejuvenation by young blood. In contrast to vampire stories, we have no strong experimental evidence that this is true, and there is a lot of evidence that infusing your body with someone else’s blood has severe side effects (even if it is cell-free).

Mike: Translational research!

Some evidence suggests dilution is the most likely reason that young blood has some beneficial effects; what are your thoughts on this recent study [6] in rats that shows improved hepatic function partially via the restoration of autophagy?

Irina: There are certainly “young” blood factors that are beneficial, not just a dilution of the old blood, and this benefit differs from organ to organ. We have published on improved liver regeneration, reduced fibrosis and adiposity by transfusion of old mice with young blood, but these are genetically matched animals, and in people, we do not have our own identical but much younger twins [7].

If dilution is also playing a role here, then can we expect similar or better results from calibrating aged blood?

Irina: Yes, and our work in progress supports the idea.

In your 2015 paper, you identified that TGF-β1 can be either pro-youthful or pro-aging in nature, depending on its level [8]. In the study, you periodically used an Alk-5 inhibitor to reduce TGF-β1 levels and promote regeneration in various tissues. In the study, you showed that TGF-β1 was important in myogenesis and neurogenesis; is there reason to believe that this mechanism might be ubiquitous in all tissues?

Irina: Yes, because TGF-β1 receptors are present in most cells and tissues.

Also, TGF-β1 is only one of a number of factors that need to be carefully balanced in order to create a pro-youthful signalling environment. How many factors do you believe we will need to calibrate?

Irina: There will be a certain benefit from calibrating just TGF-beta 1, but also additional benefits from more than one or just TGF-beta.

How do you propose to balance this cocktail of factors in aged blood to promote a youthful tissue environment?

Irina: We are working on the NextGen blood apheresis devices to accomplish this.

So, you are adapting the plasmapheresis process to effectively “scrub” aged blood clean and then return it to the patient. This would remove the need to transfuse blood from young people, as your own blood could be filtered and returned to you, and no immune reaction either, right?

Irina: Accurate.

This plasmapheresis technique is already approved by the FDA, we believe, so this should help you to develop your project faster, right?

Irina: Exactly.

Do you think a small molecule approach is a viable and, more importantly, a logistically practical approach to calibrate all these factors compared to filtering aged blood?

Irina: Yes, it is a very feasible alternative to the NextGen apheresis that we are working and publishing on.

It is thought that altered signaling is caused by other aging hallmarks higher up in the chain of events; even if we can “scrub” aged blood clean, is it likely to have a long-lasting effect, or would the factors reach pro-aging levels fairly quickly again if nothing is done about the other hallmarks antagonizing them?

Irina: That needs to be established experimentally, but due to the many feedback loops at the levels of proteins, genes and epigenetics, the acquired youthful state might persist.

Ultimately, could a wearable or an implanted device that constantly filters the blood be the solution to these quickly accumulating factors?

Irina: Maybe, but the first step of a day at a NextGen apheresis clinic once every few months might be more realistic.

Filtering seems to be a far more practical solution, so how are you progressing on the road to clinical trials?

Irina: We are collaborating with Dr. Dobri Kiprov, who is a practicing blood apheresis physician with 35 years of experience, and he is interested in repositioning this treatment for alleviating age-related illnesses.

Senolytics and removing senescent cells and the resulting inflammation they cause during the aging process has become a hot topic in the last year or so. What are your thoughts on senolytics as a potential co-therapy with a blood filtering approach?

Irina: Might be good, but we should be careful, as p16 is a normal, good gene that is needed for many productive activities by many cells.

What do you think it will take for the government to fully support the push to develop rejuvenation biotechnology?

Irina: Clear understanding of the current progress and separating the real science from snake oil is very important for guiding funding toward realistic clinical translation and away from the myth and hype.

The field is making amazing progress, but, sadly, it is plagued by snake oil. As much as an “anti-aging free market” encourages innovation, it also encourages hucksters. How can a member of the public tell the difference between credible science and snake oil?

Irina: I was thinking for some time about starting a popularized journal club webpage where ordinary people can see what we typically critically point out in the lab setting about published papers and clinical trials.

How can our readers learn more about your work and support your research?

Irina: The new Conboy lab website is coming up; meanwhile, contact me and Dr. Mike at iconboy@berkeley.edu and conboymj@berkeley.edu

Conclusion

We would like to thank Irina and Michael for taking the time to answer our questions and for providing the readers with a fascinating insight into their work.

Literature

[1] Conboy, I. M., Conboy, M. J., Smythe, G. M., & Rando, T. A. (2003). Notch-mediated restoration of regenerative potential to aged muscle. Science, 302(5650), 1575-1577.

[2] Conboy, I. M., Conboy, M. J., Wagers, A. J., Girma, E. R., Weissman, I. L., & Rando, T. A. (2005). Rejuvenation of aged progenitor cells by exposure to a young systemic environment. Nature, 433(7027), 760-764.

[3] Yousef, H., Conboy, M. J., Morgenthaler, A., Schlesinger, C., Bugaj, L., Paliwal, P., … & Schaffer, D. (2015). Systemic attenuation of the TGF-β pathway by a single drug simultaneously rejuvenates hippocampal neurogenesis and myogenesis in the same old mammal. Oncotarget, 6(14), 11959.

[4] Rebo, J., Mehdipour, M., Gathwala, R., Causey, K., Liu, Y., Conboy, M. J., & Conboy, I. M. (2016). A single heterochronic blood exchange reveals rapid inhibition of multiple tissues by old blood. Nature communications, 7.

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

[6] Liu, A., Guo, E., Yang, J., Yang, Y., Liu, S., Jiang, X., … & Gewirtz, D. A. (2017). Young plasma reverses age‐dependent alterations in hepatic function through the restoration of autophagy. Aging cell.

[7] Rebo, J., Mehdipour, M., Gathwala, R., Causey, K., Liu, Y., Conboy, M. J., & Conboy, I. M. (2016). A single heterochronic blood exchange reveals rapid inhibition of multiple tissues by old blood. Nature communications, 7.

[8] Yousef, H., Conboy, M. J., Morgenthaler, A., Schlesinger, C., Bugaj, L., Paliwal, P., … & Schaffer, D. (2015). Systemic attenuation of the TGF-β pathway by a single drug simultaneously rejuvenates hippocampal neurogenesis and myogenesis in the same old mammal. Oncotarget, 6(14), 11959.

 

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.