Browsed by
Tag: stem cells

Five Tangible Steps We Can Take in 2018 to Reach Indefinite Longevity – Article by Bobby Ridge

Five Tangible Steps We Can Take in 2018 to Reach Indefinite Longevity – Article by Bobby Ridge

Bobby Ridge


You may have finally just discovered this most important conversation, or you may be a transhumanist veteran. When I research others’ attempts to articulate Transhumanism, I observe that they tend to either discuss the intangible philosophy, or they will offer an hour plus of hard science. The purpose of this article is to provide 5 tangible ways in which right now you can get involved with Transhumanism and take real steps towards extending your healthy lifespan.

I am not a doctor, so I am not providing medical advice. It is recommended that any person considering significant health-related decisions take into account his or her personal circumstances and consult a knowledgeable medical professional. I am merely a normal guy providing some salient information I have discovered during my Transhumanist journey. Here are the 5 tangible ways some of us might, in the appropriate circumstances, extend our healthy lifespans right now:

  1. Whole genome sequencing
  2. Stem-cell therapy
  3. Sign the international ban on AI weaponry
  4. Become a member of Transhumanist organizations
  5. Cryonics

There are other tangible ways to extend our healthy lifespans right now, but these are ones I have done a significant amount of research into. Transhumanism and the Singularity will transform every single person’s life whether they want this transformation to happen or not, so constant research is essential to being as prepared as possible for this next few decades. Let’s take a closer look at those five tangible ways to extend our healthy lifespans right now.   

  • Whole Genome Sequencing

Getting our whole genomes sequenced is a great step to increasing our healthy lifespans for so many reasons. One reason is because of how cheap it is relative to the recent past. It cost $3 billion to have one’s genome sequenced in 2001. Since genome sequencing is an exponentially advancing technology like Ray Kurzweil predicted, in 2015 it only cost $1000 to sequence someone’s genome [1]. Most importantly, getting our whole genomes sequenced prevents diseases. I am not talking about the type of prevention where your parents and grandparents had heart attacks, so now you must eat specific cereal to prevent a heart attack. I am talking about complete prevention, e.g., the scientists at Human Longevity Inc. (HLI) only accept into their testing program people who are considered healthy by contemporary modern medicine. Even though members are considered “healthy,” HLI still finds some sort of hidden pathology in 40% of people tested. With their advanced scanning machines, whole genome sequencing process, and future application of machine learning to all their data, they are turning medicine into proactive, preventative, personalized, and predictive, rather than the contemporary healthcare system being reactive, disease-management-oriented, generalized, and costly.

Figure 1. HLI transforming the modern health system.  [2]

With this incredible approach, HLI has had a 100% diagnosis rate, and all their findings have been successfully treated. They have whole lists of stories, such as the story when a doctor considered healthy came into to get scanned by HLI, and they found a 5cm tumor under his tail bone; a week later he had it removed. He was later told that if he did not have it removed in 6 months, it would have metastasized [3]. The HLI offers two health packages, the Health Nucleus X for $4,950.00 [4] and the Health Nucleus X Platinum for $25,000.00 [5]. This may sound expensive, but with the exponential decrease in genome sequencing cost and with further democratization of HNX clinics, the price will drop quickly. But there is no time to waste, because contemporary health statistics are not on our side. We may feel healthy and are even told we are healthy by a hospital, but getting our whole genomes sequenced is how we really know.

Here is a link to HLI: https://www.humanlongevity.com/

  • Stem-Cell Therapy

Stem cells are so exciting, if you don’t feel excitement after reading this part of the article, then you did not fully comprehend the article. According to Daniel Kota, “We have reached a critical point. We see a massive number of different stem-cell treatments out there. The only thing between stem cell therapies and us, is regulatory agencies, such as the FDA in the US. But the number of stem-cell treatments out there are getting so overwhelming that some are just falling through the cracks” [6]. Not only can stem-cell therapy provide a massive number of treatments, but it may even have age-reversal effects. Before I explain these effects in more detail, the stem-cell therapies I am going to describe have not gone through FDA approval yet in the US, so it would require you to be a medical tourist for now. So, a lot of research and many discussions with your physician are essential before actively seeking any sort of therapy. As we age the number and function of mesenchymal stem cells (MSCs) decrease. MSCs are the major modulators of our health and homeostasis. It is also important to note that MSCs are not the controversial embryonic stem cells (EMCs). MSCs are not only more ethical to use, because the extraction process does not require the destruction of a human embryo, but research has found MSCs to be significantly better to use for human treatments, relative to EMCs. So, back to how MSCs help with age-related diseases.

Figure 2. The amount of MSCs in our body decrease over time.

A shown in Figure 2, when we are born, we have a certain amount of MSCs, and they divide at their fastest rate. The number of cells and their rate of division decrease over time. So, let’s say you’re 80 years old and you need 10,000 MSCs to recover from some pathology, but you only have a 1,000 – well you can clearly see that the 80-year-old will not have enough MSCs [7]. So what researchers and doctors are doing are just placing stem cells back into the body, e.g., at the Stem Cell Institute, the medical clinic in Panama City, Panama, they inject stem cells in the specific area of bodily damage, such as a hip fracture. They also intravenously inject stem cells into patients. Matter of fact, this is what Mel Gibson’s father did. He was 92 years old, on his death bed, and the genius Mel Gibson had his personal physician talk with Dr. Neil Riordan, and soon thereafter, Mel’s Dad was in Panama getting stem cell injections in his hip and intravenously. Now his father is thriving at 99 years of age! [8] That is amazing! There are a large number of similar stories ranging from curing complete quadriplegia to low-functioning children with autism becoming high-functioning, even to a point where it is barely noticeable that the child has autism. Dr. Riordan, the founder of Stem Cell Institute, wrote an amazing book called Stem Cell Therapy: A Rising Tide: How Stem Cells Are Disrupting Medicine and Transforming Lives, that explains MSC therapy in a very easy-to-understand and passionate manner. I highly recommend it. Prices for the stem-cell treatment depend on the specific pathology, but general intravenous injections would cost around $20,000.

Here is a link to the Stem Cell Institute: https://www.cellmedicine.com/

Here is a link to Dr. Neil Riordan speaking: https://www.youtube.com/watch?v=cLKOddCPs9I

  • Sign the International Ban on AI Weaponry

The only other epochs that were as important as the next two decades of artificial intelligence (AI) development were when life first began 4.2 billion years ago and when the universe began 13.8 billion years ago. According to Andrew Ng, “AI is the new electricity. About a hundred years ago, we did not have widespread access to electricity in the US, but with the rise of electricity, it transformed every industry. Agriculture was transformed through the rise of refrigeration, communications was transformed by telegraph, manufacturing was transformed by the electric motor, healthcare was transformed. In all these industries you have a hard time imagining how to run these things without electricity. AI technology, especially deep learning, has now advanced to a point where we see a surprisingly clear path for it to also transform every industry” [9]. Similar statements have been uttered from many of the tech titans, e.g., Sundar Pichai, Jeff Bezos, and Elon Musk [10] [11] [12]. Like every technology, AI can either be used for good or evil. Well, the amount of good AI can bring humanity is probably infinite. It will help us cure all diseases, personalize teaching to children, drive our cars, take away our soul-draining jobs, and SO MUCH MORE. To make an ideal AI future come to fruition, we must properly steer this most powerful technological development. The amount of bad that AI can bring humanity, if misapplied, is an existential risk, possibly worse. There are already AI weapons being successfully made, e.g., The Kalashnikov Bureau weapons manufacturing company announced that it has recently invented an unmanned ground vehicle (UGV), which field tests have already shown better than human level intelligence. China recently began field-testing cruise missiles with AI and autonomous capabilities, and a few companies are getting very close to having AI autopilot operating to control the flight envelope at hypersonic speeds. [13]. According to Reuters, “The Pentagon’s fiscal 2017 budget request will include $12 billion to $15 billion to fund war gaming, experimentation and the demonstration of new technologies aimed at ensuring a continued military edge over China and Russia” [14]. Vladimir Putin publicly announced that “Artificial intelligence is the future. Not only for Russia, but for all of humankind. It comes with colossal opportunities, but also threats that are difficult to predict. Whoever becomes the leader in this sphere, will become the ruler of the world” [15]. The government of China laid out a timeline to beat the US in this AI arms race, aiming by 2020 to have caught up to the AI industry, by 2025 to be ahead of the US, and by 2030 to dominate the industry of AI. One tangible way to prevent an AI arms race is to sign the international ban on AI weaponry.

Here is a link to the open letter supporting an international ban on AI weaponry: https://futureoflife.org/open-letter-autonomous-weapons/

  • Transhumanist organizations

It almost seems like every week there is a new Transhumanist organization emerging. I guess people are finally figuring out how quintessential transhumanist principles are for the future of humanity. I recommend you search Wikipedia, because they have a great database of Transhumanist organizations.

Becoming a member of the United States Transhumanist Party (USTP) and all the other transhumanist parties and organizations is a great way to stay informed about all the exponentially accelerating science and technology [1]. The USTP’s central tenet is to place science, health, and technology at the forefront of American Politics. The accelerated technological advancement that is occurring will cause such enormous change, but for some reason our political leaders mainly focus on providing the American people with momentary uplifting feelings, and their advocacies encompass going back to the old days. Well instead, they should be placing all their resources into educating and preparing Americans for this massive transformation we are all about to witness in the next few decades. Please become a member of the USTP and help us get the word out about Transhumanism and the Singularity for the sake of all our lives.

Here is the link to become a member of the USTP: http://transhumanist-party.org/membership/

Here is a link to H+Pedia’s list of Transhumanist political organizations: https://hpluspedia.org/wiki/Transhumanist_political_organisations

Here is a link to Wikipedia’s list of Transhumanist organizations: https://en.wikipedia.org/wiki/Category:Transhumanist_organizations

  • Cryonics

Cryonics has been around for a relatively long time. The first cryonics institute was formed in 1976, and even though cryonics has been around for so long, cryogenically preserving one’s body just has not been popularized yet by the mainstream. One would think that by 2018, we would have caught on. It is sad to think of all the millions of people that missed the chance to be preserved for the last 40 years. It is very important to have yourself and loved ones cryopreserved after death, because it will decrease the taboo, push the advancement of the technology forward, and, most importantly, you will be able to live indefinitely! Many may think that it is too expensive, and prices can range anywhere from $28,000.00 to $200,000.00, but choosing to do monthly payments makes the price very affordable [16], [17].

Here is a link to a cryonics organization – the Alcor Life Extension Foundation: https://alcor.org/

Here is a link to another cryonics organization – the Cryonics Institute: http://www.cryonics.org/

In the great Transhumanist game, the human species must unite once and for all to survive the 21st century. Ray Kurzweil gave us a map to the greatest treasure, a treasure that will buy more than happiness. It will buy us eternal love, beautiful augmentation, indefinite longevity, and maybe even utopia. It is up to us to steer this ship in the right direction and make sure we stay afloat while on this dangerous journey. I sincerely hope this information saves as many lives as possible.

Bobby Ridge is the Secretary of the United States Transhumanist Party. Read more about him here

References

  1. Kurzweil, Ray. “Ray Kurzweil — Immortality By 2045 / Global Future 2045 Congress’2013.” YouTube, 2045 Initiative, 18 Jan. 2015. https://www.youtube.com/watch?v=qlRTbl_IB-s
  2. Venter, Craig. “Dr. Craig Venter – How We Will Extend Our Lives: From Synthetic Life to Human Longevity.” YouTube.com, The Artificial Intelligence Channel, 1 Oct. 2017, https://www.youtube.com/watch?v=OfzfI2dvp3s
  3. Venter, Craig. “MIS2017: Genomics, Advanced Imaging, And The Future Of Medicine.” YouTube.com, Cleveland Clinic, 8 Nov. 2017, https://www.youtube.com/watch?v=nkUMjh1GjKs
  4. Health Nucleus X. Human Longevity, Inc. 2013. Web. 4 May 2018.
  5. Health Nucleus X Platinum. Human Longevity, Inc. 2013. Web. 4 May 2018
  6. Kota, Daniel. “Promises and Dangers of Stem Cell Therapies | Daniel Kota | TEDxBrookings.” YouTube.com, TEDx Talks., 28 Nov. 2017. https://www.youtube.com/watch?v=hsFEcBwO8O4
  7. Riordan, Neil H. Stem Cell Therapy: A Rising Tide: How Stem Cells Are Disrupting Medicine and Transforming Lives. 2017. Print.
  8. Riordan, Neil. “Golden Cells and Mesenchymal Molecules – Neil Riordan, PhD.” YouTube.com, Riordan Clinic. 15 Jan. 2018. https://www.youtube.com/watch?v=cLKOddCPs9I
  9. Ng, Andrew. “Andrew Ng – The State of Artificial Intelligence.” YouTube.com, The Artificial Intelligence Channel, 15 Dec. 2017. https://www.youtube.com/watch?v=NKpuX_yzdYs
  10. Pichai, Sundar. “Google CEO Sundar Pichai: A.I. More Important To Humanity Than Fire And Electricity | MSNBC.” YouTube.com, MSNBC. 29, Jan. 2018. https://www.youtube.com/watch?v=jxEo3Epc43Y
  11. Bezos, Jeff. “Amazon’s Jeff Bezos: Lessons in Management at I.A. Gala 2017.” YouTube.com, Expovista TV, 8 May, 2017. https://www.youtube.com/watch?v=fpDUiDQigO8
  12. Musk, Elon. “Elon Musk, National Governors Association, July 15, 2017.” YouTube.com, WordsmithFL, 16 July, 2017. https://www.youtube.com/watch?v=b3lzEQANdHk
  13. Husain, Amir. “Amir Husain: “The Sentient Machine: The Coming Age of Artificial Intelligence.”” YouTube.com. Talks at Google. 31 Jan. 2018. https://www.youtube.com/watch?v=JcC5OV_oA1s
  14. Conn, Ariel. “Pentagon Seeks $12 -$15 Billion for AI Weapons Research.” Future of life institute. FLI – Future of Life Institute, 15 Dec. 2015. Web. 4 May, 2018.
  15. Putin, Vladimir. “Whoever leads in AI will rule the world! – Putin to Russian children on Knowledge Day.” YouTube.com. Russia Insight. 4 Sep. 2017.  https://www.youtube.com/watch?v=2kggRND8c7Q].
  16. “Cryospreservation is far more affordable than you might think.” Cryonics Institute Technology for Life. Cryonics Institute. 4 May, 2018. Web 4 May, 2018.
  17. “Alcor Cryopreservation Agreement – Schedule A Required Costs and Cryopreservation Fund Minimums.” Alcor Life Extension Foundation. Alcor. Web 4 May, 2018.
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.

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.

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.