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#434792 Extending Human Longevity With ...
Lizards can regrow entire limbs. Flatworms, starfish, and sea cucumbers regrow entire bodies. Sharks constantly replace lost teeth, often growing over 20,000 teeth throughout their lifetimes. How can we translate these near-superpowers to humans?
The answer: through the cutting-edge innovations of regenerative medicine.
While big data and artificial intelligence transform how we practice medicine and invent new treatments, regenerative medicine is about replenishing, replacing, and rejuvenating our physical bodies.
In Part 5 of this blog series on Longevity and Vitality, I detail three of the regenerative technologies working together to fully augment our vital human organs.
Replenish: Stem cells, the regenerative engine of the body
Replace: Organ regeneration and bioprinting
Rejuvenate: Young blood and parabiosis
Let’s dive in.
Replenish: Stem Cells – The Regenerative Engine of the Body
Stem cells are undifferentiated cells that can transform into specialized cells such as heart, neurons, liver, lung, skin and so on, and can also divide to produce more stem cells.
In a child or young adult, these stem cells are in large supply, acting as a built-in repair system. They are often summoned to the site of damage or inflammation to repair and restore normal function.
But as we age, our supply of stem cells begins to diminish as much as 100- to 10,000-fold in different tissues and organs. In addition, stem cells undergo genetic mutations, which reduce their quality and effectiveness at renovating and repairing your body.
Imagine your stem cells as a team of repairmen in your newly constructed mansion. When the mansion is new and the repairmen are young, they can fix everything perfectly. But as the repairmen age and reduce in number, your mansion eventually goes into disrepair and finally crumbles.
What if you could restore and rejuvenate your stem cell population?
One option to accomplish this restoration and rejuvenation is to extract and concentrate your own autologous adult stem cells from places like your adipose (or fat) tissue or bone marrow.
These stem cells, however, are fewer in number and have undergone mutations (depending on your age) from their original ‘software code.’ Many scientists and physicians now prefer an alternative source, obtaining stem cells from the placenta or umbilical cord, the leftovers of birth.
These stem cells, available in large supply and expressing the undamaged software of a newborn, can be injected into joints or administered intravenously to rejuvenate and revitalize.
Think of these stem cells as chemical factories generating vital growth factors that can help to reduce inflammation, fight autoimmune disease, increase muscle mass, repair joints, and even revitalize skin and grow hair.
Over the last decade, the number of publications per year on stem cell-related research has increased 40x, and the stem cell market is expected to increase to $297 billion by 2022.
Rising research and development initiatives to develop therapeutic options for chronic diseases and growing demand for regenerative treatment options are the most significant drivers of this budding industry.
Biologists led by Kohji Nishida at Osaka University in Japan have discovered a new way to nurture and grow the tissues that make up the human eyeball. The scientists are able to grow retinas, corneas, the eye’s lens, and more, using only a small sample of adult skin.
In a Stanford study, seven of 18 stroke victims who agreed to stem cell treatments showed remarkable motor function improvements. This treatment could work for other neurodegenerative conditions such as Alzheimer’s, Parkinson’s, and ALS.
Doctors from the USC Neurorestoration Center and Keck Medicine of USC injected stem cells into the damaged cervical spine of a recently paralyzed 21-year-old man. Three months later, he showed dramatic improvement in sensation and movement of both arms.
In 2019, doctors in the U.K. cured a patient with HIV for the second time ever thanks to the efficacy of stem cells. After giving the cancer patient (who also had HIV) an allogeneic haematopoietic (e.g. blood) stem cell treatment for his Hodgkin’s lymphoma, the patient went into long-term HIV remission—18 months and counting at the time of the study’s publication.
Replace: Organ Regeneration and 3D Printing
Every 10 minutes, someone is added to the US organ transplant waiting list, totaling over 113,000 people waiting for replacement organs as of January 2019.
Countless more people in need of ‘spare parts’ never make it onto the waiting list. And on average, 20 people die each day while waiting for a transplant.
As a result, 35 percent of all US deaths (~900,000 people) could be prevented or delayed with access to organ replacements.
The excessive demand for donated organs will only intensify as technologies like self-driving cars make the world safer, given that many organ donors result from auto and motorcycle accidents. Safer vehicles mean less accidents and donations.
Clearly, replacement and regenerative medicine represent a massive opportunity.
Organ Entrepreneurs
Enter United Therapeutics CEO, Dr. Martine Rothblatt. A one-time aerospace entrepreneur (she was the founder of Sirius Satellite Radio), Rothblatt changed careers in the 1990s after her daughter developed a rare lung disease.
Her moonshot today is to create an industry of replacement organs. With an initial focus on diseases of the lung, Rothblatt set out to create replacement lungs. To accomplish this goal, her company United Therapeutics has pursued a number of technologies in parallel.
3D Printing Lungs
In 2017, United teamed up with one of the world’s largest 3D printing companies, 3D Systems, to build a collagen bioprinter and is paying another company, 3Scan, to slice up lungs and create detailed maps of their interior.
This 3D Systems bioprinter now operates according to a method called stereolithography. A UV laser flickers through a shallow pool of collagen doped with photosensitive molecules. Wherever the laser lingers, the collagen cures and becomes solid.
Gradually, the object being printed is lowered and new layers are added. The printer can currently lay down collagen at a resolution of around 20 micrometers, but will need to achieve resolution of a micrometer in size to make the lung functional.
Once a collagen lung scaffold has been printed, the next step is to infuse it with human cells, a process called recellularization.
The goal here is to use stem cells that grow on scaffolding and differentiate, ultimately providing the proper functionality. Early evidence indicates this approach can work.
In 2018, Harvard University experimental surgeon Harald Ott reported that he pumped billions of human cells (from umbilical cords and diced lungs) into a pig lung stripped of its own cells. When Ott’s team reconnected it to a pig’s circulation, the resulting organ showed rudimentary function.
Humanizing Pig Lungs
Another of Rothblatt’s organ manufacturing strategies is called xenotransplantation, the idea of transplanting an animal’s organs into humans who need a replacement.
Given the fact that adult pig organs are similar in size and shape to those of humans, United Therapeutics has focused on genetically engineering pigs to allow humans to use their organs. “It’s actually not rocket science,” said Rothblatt in her 2015 TED talk. “It’s editing one gene after another.”
To accomplish this goal, United Therapeutics made a series of investments in companies such as Revivicor Inc. and Synthetic Genomics Inc., and signed large funding agreements with the University of Maryland, University of Alabama, and New York Presbyterian/Columbia University Medical Center to create xenotransplantation programs for new hearts, kidneys, and lungs, respectively. Rothblatt hopes to see human translation in three to four years.
In preparation for that day, United Therapeutics owns a 132-acre property in Research Triangle Park and built a 275,000-square-foot medical laboratory that will ultimately have the capability to annually produce up to 1,000 sets of healthy pig lungs—known as xenolungs—from genetically engineered pigs.
Lung Ex Vivo Perfusion Systems
Beyond 3D printing and genetically engineering pig lungs, Rothblatt has already begun implementing a third near-term approach to improve the supply of lungs across the US.
Only about 30 percent of potential donor lungs meet transplant criteria in the first place; of those, only about 85 percent of those are usable once they arrive at the surgery center. As a result, nearly 75 percent of possible lungs never make it to the recipient in need.
What if these lungs could be rejuvenated? This concept informs Dr. Rothblatt’s next approach.
In 2016, United Therapeutics invested $41.8 million in TransMedics Inc., an Andover, Massachusetts company that develops ex vivo perfusion systems for donor lungs, hearts, and kidneys.
The XVIVO Perfusion System takes marginal-quality lungs that initially failed to meet transplantation standard-of-care criteria and perfuses and ventilates them at normothermic conditions, providing an opportunity for surgeons to reassess transplant suitability.
Rejuvenate Young Blood and Parabiosis
In HBO’s parody of the Bay Area tech community, Silicon Valley, one of the episodes (Season 4, Episode 5) is named “The Blood Boy.”
In this installment, tech billionaire Gavin Belson (Matt Ross) is meeting with Richard Hendricks (Thomas Middleditch) and his team, speaking about the future of the decentralized internet. A young, muscled twenty-something disrupts the meeting when he rolls in a transfusion stand and silently hooks an intravenous connection between himself and Belson.
Belson then introduces the newcomer as his “transfusion associate” and begins to explain the science of parabiosis: “Regular transfusions of the blood of a younger physically fit donor can significantly retard the aging process.”
While the sitcom is fiction, that science has merit, and the scenario portrayed in the episode is already happening today.
On the first point, research at Stanford and Harvard has demonstrated that older animals, when transfused with the blood of young animals, experience regeneration across many tissues and organs.
The opposite is also true: young animals, when transfused with the blood of older animals, experience accelerated aging. But capitalizing on this virtual fountain of youth has been tricky.
Ambrosia
One company, a San Francisco-based startup called Ambrosia, recently commenced one of the trials on parabiosis. Their protocol is simple: Healthy participants aged 35 and older get a transfusion of blood plasma from donors under 25, and researchers monitor their blood over the next two years for molecular indicators of health and aging.
Ambrosia’s founder Jesse Karmazin became interested in launching a company around parabiosis after seeing impressive data from animals and studies conducted abroad in humans: In one trial after another, subjects experience a reversal of aging symptoms across every major organ system. “The effects seem to be almost permanent,” he said. “It’s almost like there’s a resetting of gene expression.”
Infusing your own cord blood stem cells as you age may have tremendous longevity benefits. Following an FDA press release in February 2019, Ambrosia halted its consumer-facing treatment after several months of operation.
Understandably, the FDA raised concerns about the practice of parabiosis because to date, there is a marked lack of clinical data to support the treatment’s effectiveness.
Elevian
On the other end of the reputability spectrum is a startup called Elevian, spun out of Harvard University. Elevian is approaching longevity with a careful, scientifically validated strategy. (Full Disclosure: I am both an advisor to and investor in Elevian.)
CEO Mark Allen, MD, is joined by a dozen MDs and Ph.Ds out of Harvard. Elevian’s scientific founders started the company after identifying specific circulating factors that may be responsible for the “young blood” effect.
One example: A naturally occurring molecule known as “growth differentiation factor 11,” or GDF11, when injected into aged mice, reproduces many of the regenerative effects of young blood, regenerating heart, brain, muscles, lungs, and kidneys.
More specifically, GDF11 supplementation reduces age-related cardiac hypertrophy, accelerates skeletal muscle repair, improves exercise capacity, improves brain function and cerebral blood flow, and improves metabolism.
Elevian is developing a number of therapeutics that regulate GDF11 and other circulating factors. The goal is to restore our body’s natural regenerative capacity, which Elevian believes can address some of the root causes of age-associated disease with the promise of reversing or preventing many aging-related diseases and extending the healthy lifespan.
Conclusion
In 1992, futurist Leland Kaiser coined the term “regenerative medicine”:
“A new branch of medicine will develop that attempts to change the course of chronic disease and in many instances will regenerate tired and failing organ systems.”
Since then, the powerful regenerative medicine industry has grown exponentially, and this rapid growth is anticipated to continue.
A dramatic extension of the human healthspan is just over the horizon. Soon, we’ll all have the regenerative superpowers previously relegated to a handful of animals and comic books.
What new opportunities open up when anybody, anywhere, and at anytime can regenerate, replenish, and replace entire organs and metabolic systems on command?
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#434599 This AI Can Tell Your Age by Analyzing ...
The plethora of bacteria and other tiny organisms that live in your gut, often referred to as the gut microbiome, don’t just help you digest food and fight disease. As detailed in a new study, they also provide a very accurate biological clock that shows your physical age—a fact that may open up wide-ranging possibilities for health and longevity studies.
Combining Machine Learning and Your Gut
The link between the gut biome and age is described by longevity researcher Alex Zhavoronkov and a team of his colleagues at Insilico Medicine, an artificial intelligence startup focused on drug discovery, biomarker development, and aging research.
Relatively little is known about how our gut biomes transition from one stage to another as we age, or about links between our age and the state of our gut biomes. In their paper, which is awaiting peer review but can be found on the preprint server bioRxiv, the team describes how they examined 3,663 curated samples of gut bacteria from 1,165 healthy people, aged 20-90, from countries in Europe, Asia, and North America. Roughly a third of samples came from the 20-39 age group, a third from individuals between 40-59, and a third from people between 60-90 years old.
A deep learning algorithm was then trained on data on 1,673 different microbial species from 90 percent of the samples. The AI was then tasked with predicting the ages of the remaining 10 percent of participants solely from data on their gut bacteria.
The Accurate Bacterial Clock
The results, described as the first method to predict a human’s chronological age via gut microbiota analysis, showed that the system was able to predict age to within four years based on the gut bacteria data. Furthermore, the results seem to indicate that 39 of the microbial species analyzed are particularly important in relation to accurately predicting age.
The study also showed that our gut microbiomes change over time. While some microbes’ numbers dwindle as we age, others seem to become more abundant. Age is not the only factor that influences the prevalence of different types of bacteria in a person’s digestive system. What you eat, how you sleep, and how physically active you are are all thought to be contributing factors.
Science Magquotes Zhavoronkov as stating that the study could lay the foundation for a “microbiome aging clock” that could serve as a baseline in future research on how a person’s gut ages and how medicine, diet, and alcohol consumption affect longevity.
Living Longer, Better
Studies of our microbiome’s influence on longevity add another dimension to our understanding of how and why we age. Other avenues of study include looking at the length of telomeres, the tips of chromosomes that are believed to play an important role in the aging process, and our DNA.
The same can be said of the role microbiomes play in relation to illnesses and conditions including allergies, diabetes, some types of cancer, and psychological states such as depression. Scientists at Harvard are even developing genetically engineered ‘telephone’ bacteria that would be able to gather precise information about the state of the gut microbiome.
A positive side effect of many of the studies is that alongside dedicated microbiome data collection efforts, they add new data—the food of AI. While we are already gaining a better understanding of the gut biome, it is not a large leap of logic to predict that AI will feast on the new data and assist us in getting an even keener understanding of what is going on in our gut and what it means for our health.
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#434569 From Parkour to Surgery, Here Are the ...
The robot revolution may not be here quite yet, but our mechanical cousins have made some serious strides. And now some of the leading experts in the field have provided a rundown of what they see as the 10 most exciting recent developments.
Compiled by the editors of the journal Science Robotics, the list includes some of the most impressive original research and innovative commercial products to make a splash in 2018, as well as a couple from 2017 that really changed the game.
1. Boston Dynamics’ Atlas doing parkour
It seems like barely a few months go by without Boston Dynamics rewriting the book on what a robot can and can’t do. Last year they really outdid themselves when they got their Atlas humanoid robot to do parkour, leaping over logs and jumping between wooden crates.
Atlas’s creators have admitted that the videos we see are cherry-picked from multiple attempts, many of which don’t go so well. But they say they’re meant to be inspirational and aspirational rather than an accurate picture of where robotics is today. And combined with the company’s dog-like Spot robot, they are certainly pushing boundaries.
2. Intuitive Surgical’s da Vinci SP platform
Robotic surgery isn’t new, but the technology is improving rapidly. Market leader Intuitive’s da Vinci surgical robot was first cleared by the FDA in 2000, but since then it’s come a long way, with the company now producing three separate systems.
The latest addition is the da Vinci SP (single port) system, which is able to insert three instruments into the body through a single 2.5cm cannula (tube) bringing a whole new meaning to minimally invasive surgery. The system was granted FDA clearance for urological procedures last year, and the company has now started shipping the new system to customers.
3. Soft robot that navigates through growth
Roboticists have long borrowed principles from the animal kingdom, but a new robot design that mimics the way plant tendrils and fungi mycelium move by growing at the tip has really broken the mold on robot navigation.
The editors point out that this is the perfect example of bio-inspired design; the researchers didn’t simply copy nature, they took a general principle and expanded on it. The tube-like robot unfolds from the front as pneumatic pressure is applied, but unlike a plant, it can grow at the speed of an animal walking and can navigate using visual feedback from a camera.
4. 3D printed liquid crystal elastomers for soft robotics
Soft robotics is one of the fastest-growing sub-disciplines in the field, but powering these devices without rigid motors or pumps is an ongoing challenge. A variety of shape-shifting materials have been proposed as potential artificial muscles, including liquid crystal elastomeric actuators.
Harvard engineers have now demonstrated that these materials can be 3D printed using a special ink that allows the designer to easily program in all kinds of unusual shape-shifting abilities. What’s more, their technique produces actuators capable of lifting significantly more weight than previous approaches.
5. Muscle-mimetic, self-healing, and hydraulically amplified actuators
In another effort to find a way to power soft robots, last year researchers at the University of Colorado Boulder designed a series of super low-cost artificial muscles that can lift 200 times their own weight and even heal themselves.
The devices rely on pouches filled with a liquid that makes them contract with the force and speed of mammalian skeletal muscles when a voltage is applied. The most promising for robotics applications is the so-called Peano-HASEL, which features multiple rectangular pouches connected in series that contract linearly, just like real muscle.
6. Self-assembled nanoscale robot from DNA
While you may think of robots as hulking metallic machines, a substantial number of scientists are working on making nanoscale robots out of DNA. And last year German researchers built the first remote-controlled DNA robotic arm.
They created a length of tightly-bound DNA molecules to act as the arm and attached it to a DNA base plate via a flexible joint. Because DNA carries a charge, they were able to get the arm to swivel around like the hand of a clock by applying a voltage and switch direction by reversing that voltage. The hope is that this arm could eventually be used to build materials piece by piece at the nanoscale.
7. DelFly nimble bioinspired robotic flapper
Robotics doesn’t only borrow from biology—sometimes it gives back to it, too. And a new flapping-winged robot designed by Dutch engineers that mimics the humble fruit fly has done just that, by revealing how the animals that inspired it carry out predator-dodging maneuvers.
The lab has been building flapping robots for years, but this time they ditched the airplane-like tail used to control previous incarnations. Instead, they used insect-inspired adjustments to the motions of its twin pairs of flapping wings to hover, pitch, and roll with the agility of a fruit fly. That has provided a useful platform for investigating insect flight dynamics, as well as more practical applications.
8. Soft exosuit wearable robot
Exoskeletons could prevent workplace injuries, help people walk again, and even boost soldiers’ endurance. Strapping on bulky equipment isn’t ideal, though, so researchers at Harvard are working on a soft exoskeleton that combines specially-designed textiles, sensors, and lightweight actuators.
And last year the team made an important breakthrough by combining their novel exoskeleton with a machine-learning algorithm that automatically tunes the device to the user’s particular walking style. Using physiological data, it is able to adjust when and where the device needs to deliver a boost to the user’s natural movements to improve walking efficiency.
9. Universal Robots (UR) e-Series Cobots
Robots in factories are nothing new. The enormous mechanical arms you see in car factories normally have to be kept in cages to prevent them from accidentally crushing people. In recent years there’s been growing interest in “co-bots,” collaborative robots designed to work side-by-side with their human colleagues and even learn from them.
Earlier this year saw the demise of ReThink robotics, the pioneer of the approach. But the simple single arm devices made by Danish firm Universal Robotics are becoming ubiquitous in workshops and warehouses around the world, accounting for about half of global co-bot sales. Last year they released their latest e-Series, with enhanced safety features and force/torque sensing.
10. Sony’s aibo
After a nearly 20-year hiatus, Sony’s robotic dog aibo is back, and it’s had some serious upgrades. As well as a revamp to its appearance, the new robotic pet takes advantage of advances in AI, with improved environmental and command awareness and the ability to develop a unique character based on interactions with its owner.
The editors note that this new context awareness mark the device out as a significant evolution in social robots, which many hope could aid in childhood learning or provide companionship for the elderly.
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Posted in Human Robots