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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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Posted in Human Robots
#434701 3 Practical Solutions to Offset ...
In recent years, the media has sounded the alarm about mass job loss to automation and robotics—some studies predict that up to 50 percent of current jobs or tasks could be automated in coming decades. While this topic has received significant attention, much of the press focuses on potential problems without proposing realistic solutions or considering new opportunities.
The economic impacts of AI, robotics, and automation are complex topics that require a more comprehensive perspective to understand. Is universal basic income, for example, the answer? Many believe so, and there are a number of experiments in progress. But it’s only one strategy, and without a sustainable funding source, universal basic income may not be practical.
As automation continues to accelerate, we’ll need a multi-pronged approach to ease the transition. In short, we need to update broad socioeconomic strategies for a new century of rapid progress. How, then, do we plan practical solutions to support these new strategies?
Take history as a rough guide to the future. Looking back, technology revolutions have three themes in common.
First, past revolutions each produced profound benefits to productivity, increasing human welfare. Second, technological innovation and technology diffusion have accelerated over time, each iteration placing more strain on the human ability to adapt. And third, machines have gradually replaced more elements of human work, with human societies adapting by moving into new forms of work—from agriculture to manufacturing to service, for example.
Public and private solutions, therefore, need to be developed to address each of these three components of change. Let’s explore some practical solutions for each in turn.
Figure 1. Technology’s structural impacts in the 21st century. Refer to Appendix I for quantitative charts and technological examples corresponding to the numbers (1-22) in each slice.
Solution 1: Capture New Opportunities Through Aggressive Investment
The rapid emergence of new technology promises a bounty of opportunity for the twenty-first century’s economic winners. This technological arms race is shaping up to be a global affair, and the winners will be determined in part by who is able to build the future economy fastest and most effectively. Both the private and public sectors have a role to play in stimulating growth.
At the country level, several nations have created competitive strategies to promote research and development investments as automation technologies become more mature.
Germany and China have two of the most notable growth strategies. Germany’s Industrie 4.0 plan targets a 50 percent increase in manufacturing productivity via digital initiatives, while halving the resources required. China’s Made in China 2025 national strategy sets ambitious targets and provides subsidies for domestic innovation and production. It also includes building new concept cities, investing in robotics capabilities, and subsidizing high-tech acquisitions abroad to become the leader in certain high-tech industries. For China, specifically, tech innovation is driven partially by a fear that technology will disrupt social structures and government control.
Such opportunities are not limited to existing economic powers. Estonia’s progress after the breakup of the Soviet Union is a good case study in transitioning to a digital economy. The nation rapidly implemented capitalistic reforms and transformed itself into a technology-centric economy in preparation for a massive tech disruption. Internet access was declared a right in 2000, and the country’s classrooms were outfitted for a digital economy, with coding as a core educational requirement starting at kindergarten. Internet broadband speeds in Estonia are among the fastest in the world. Accordingly, the World Bank now ranks Estonia as a high-income country.
Solution 2: Address Increased Rate of Change With More Nimble Education Systems
Education and training are currently not set for the speed of change in the modern economy. Schools are still based on a one-time education model, with school providing the foundation for a single lifelong career. With content becoming obsolete faster and rapidly escalating costs, this system may be unsustainable in the future. To help workers more smoothly transition from one job into another, for example, we need to make education a more nimble, lifelong endeavor.
Primary and university education may still have a role in training foundational thinking and general education, but it will be necessary to curtail rising price of tuition and increase accessibility. Massive open online courses (MooCs) and open-enrollment platforms are early demonstrations of what the future of general education may look like: cheap, effective, and flexible.
Georgia Tech’s online Engineering Master’s program (a fraction of the cost of residential tuition) is an early example in making university education more broadly available. Similarly, nanodegrees or microcredentials provided by online education platforms such as Udacity and Coursera can be used for mid-career adjustments at low cost. AI itself may be deployed to supplement the learning process, with applications such as AI-enhanced tutorials or personalized content recommendations backed by machine learning. Recent developments in neuroscience research could optimize this experience by perfectly tailoring content and delivery to the learner’s brain to maximize retention.
Finally, companies looking for more customized skills may take a larger role in education, providing on-the-job training for specific capabilities. One potential model involves partnering with community colleges to create apprenticeship-style learning, where students work part-time in parallel with their education. Siemens has pioneered such a model in four states and is developing a playbook for other companies to do the same.
Solution 3: Enhance Social Safety Nets to Smooth Automation Impacts
If predicted job losses to automation come to fruition, modernizing existing social safety nets will increasingly become a priority. While the issue of safety nets can become quickly politicized, it is worth noting that each prior technological revolution has come with corresponding changes to the social contract (see below).
The evolving social contract (U.S. examples)
– 1842 | Right to strike
– 1924 | Abolish child labor
– 1935 | Right to unionize
– 1938 | 40-hour work week
– 1962, 1974 | Trade adjustment assistance
– 1964 | Pay discrimination prohibited
– 1970 | Health and safety laws
– 21st century | AI and automation adjustment assistance?
Figure 2. Labor laws have historically adjusted as technology and society progressed
Solutions like universal basic income (no-strings-attached monthly payout to all citizens) are appealing in concept, but somewhat difficult to implement as a first measure in countries such as the US or Japan that already have high debt. Additionally, universal basic income may create dis-incentives to stay in the labor force. A similar cautionary tale in program design was the Trade Adjustment Assistance (TAA), which was designed to protect industries and workers from import competition shocks from globalization, but is viewed as a missed opportunity due to insufficient coverage.
A near-term solution could come in the form of graduated wage insurance (compensation for those forced to take a lower-paying job), including health insurance subsidies to individuals directly impacted by automation, with incentives to return to the workforce quickly. Another topic to tackle is geographic mismatch between workers and jobs, which can be addressed by mobility assistance. Lastly, a training stipend can be issued to individuals as means to upskill.
Policymakers can intervene to reverse recent historical trends that have shifted incomes from labor to capital owners. The balance could be shifted back to labor by placing higher taxes on capital—an example is the recently proposed “robot tax” where the taxation would be on the work rather than the individual executing it. That is, if a self-driving car performs the task that formerly was done by a human, the rideshare company will still pay the tax as if a human was driving.
Other solutions may involve distribution of work. Some countries, such as France and Sweden, have experimented with redistributing working hours. The idea is to cap weekly hours, with the goal of having more people employed and work more evenly spread. So far these programs have had mixed results, with lower unemployment but high costs to taxpayers, but are potential models that can continue to be tested.
We cannot stop growth, nor should we. With the roles in response to this evolution shifting, so should the social contract between the stakeholders. Government will continue to play a critical role as a stabilizing “thumb” in the invisible hand of capitalism, regulating and cushioning against extreme volatility, particularly in labor markets.
However, we already see business leaders taking on some of the role traditionally played by government—thinking about measures to remedy risks of climate change or economic proposals to combat unemployment—in part because of greater agility in adapting to change. Cross-disciplinary collaboration and creative solutions from all parties will be critical in crafting the future economy.
Note: The full paper this article is based on is available here.
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Posted in Human Robots
#434580 How Genome Sequencing and Senolytics Can ...
The causes of aging are extremely complex and unclear. With the dramatic demonetization of genome reading and editing over the past decade, and Big Pharma, startups, and the FDA starting to face aging as a disease, we are starting to find practical ways to extend our healthspan.
Here, in Part 2 of a series of blogs on longevity and vitality, I explore how genome sequencing and editing, along with new classes of anti-aging drugs, are augmenting our biology to further extend our healthy lives.
In this blog I’ll cover two classes of emerging technologies:
Genome Sequencing and Editing;
Senolytics, Nutraceuticals & Pharmaceuticals.
Let’s dive in.
Genome Sequencing & Editing
Your genome is the software that runs your body.
A sequence of 3.2 billion letters makes you “you.” These base pairs of A’s, T’s, C’s, and G’s determine your hair color, your height, your personality, your propensity to disease, your lifespan, and so on.
Until recently, it’s been very difficult to rapidly and cheaply “read” these letters—and even more difficult to understand what they mean.
Since 2001, the cost to sequence a whole human genome has plummeted exponentially, outpacing Moore’s Law threefold. From an initial cost of $3.7 billion, it dropped to $10 million in 2006, and to $5,000 in 2012.
Today, the cost of genome sequencing has dropped below $500, and according to Illumina, the world’s leading sequencing company, the process will soon cost about $100 and take about an hour to complete.
This represents one of the most powerful and transformative technology revolutions in healthcare.
When we understand your genome, we’ll be able to understand how to optimize “you.”
We’ll know the perfect foods, the perfect drugs, the perfect exercise regimen, and the perfect supplements, just for you.
We’ll understand what microbiome types, or gut flora, are ideal for you (more on this in a later blog).
We’ll accurately predict how specific sedatives and medicines will impact you.
We’ll learn which diseases and illnesses you’re most likely to develop and, more importantly, how to best prevent them from developing in the first place (rather than trying to cure them after the fact).
CRISPR Gene Editing
In addition to reading the human genome, scientists can now edit a genome using a naturally-occurring biological system discovered in 1987 called CRISPR/Cas9.
Short for Clustered Regularly Interspaced Short Palindromic Repeats and CRISPR-associated protein 9, the editing system was adapted from a naturally-occurring defense system found in bacteria.
Here’s how it works:
The bacteria capture snippets of DNA from invading viruses (or bacteriophage) and use them to create DNA segments known as CRISPR arrays.
The CRISPR arrays allow the bacteria to “remember” the viruses (or closely related ones), and defend against future invasions.
If the viruses attack again, the bacteria produce RNA segments from the CRISPR arrays to target the viruses’ DNA. The bacteria then use Cas9 to cut the DNA apart, which disables the virus.
Most importantly, CRISPR is cheap, quick, easy to use, and more accurate than all previous gene editing methods. As a result, CRISPR/Cas9 has swept through labs around the world as the way to edit a genome.
A short search in the literature will show an exponential rise in the number of CRISPR-related publications and patents.
2018: Filled With CRISPR Breakthroughs
Early results are impressive. Researchers from the University of Chicago recently used CRISPR to genetically engineer cocaine resistance into mice.
Researchers at the University of Texas Southwestern Medical Center used CRISPR to reverse the gene defect causing Duchenne muscular dystrophy (DMD) in dogs (DMD is the most common fatal genetic disease in children).
With great power comes great responsibility, and moral and ethical dilemmas.
In 2015, Chinese scientists sparked global controversy when they first edited human embryo cells in the lab with the goal of modifying genes that would make the child resistant to smallpox, HIV, and cholera.
Three years later, in November 2018, researcher He Jiankui informed the world that the first set of CRISPR-engineered female twins had been delivered.
To accomplish his goal, Jiankui deleted a region of a receptor on the surface of white blood cells known as CCR5, introducing a rare, natural genetic variation that makes it more difficult for HIV to infect its favorite target, white blood cells.
Setting aside the significant ethical conversations, CRISPR will soon provide us the tools to eliminate diseases, create hardier offspring, produce new environmentally resistant crops, and even wipe out pathogens.
Senolytics, Nutraceuticals & Pharmaceuticals
Over the arc of your life, the cells in your body divide until they reach what is known as the Hayflick limit, or the number of times a normal human cell population will divide before cell division stops, which is typically about 50 divisions.
What normally follows next is programmed cell death or destruction by the immune system. A very small fraction of cells, however, become senescent cells and evade this fate to linger indefinitely.
These lingering cells secrete a potent mix of molecules that triggers chronic inflammation, damages the surrounding tissue structures, and changes the behavior of nearby cells for the worse.
Senescent cells appear to be one of the root causes of aging, causing everything from fibrosis and blood vessel calcification, to localized inflammatory conditions such as osteoarthritis, to diminished lung function.
Fortunately, both the scientific and entrepreneurial communities have begun to work on senolytic therapies, moving the technology for selectively destroying senescent cells out of the laboratory and into a half-dozen startup companies.
Prominent companies in the field include the following:
Unity Biotechnology is developing senolytic medicines to selectively eliminate senescent cells with an initial focus on delivering localized therapy in osteoarthritis, ophthalmology and pulmonary disease.
Oisin Biotechnologiesis pioneering a programmable gene therapy that can destroy cells based on their internal biochemistry.
SIWA Therapeuticsis working on an immunotherapy approach to the problem of senescent cells.
In recent years, researchers have identified or designed a handful of senolytic compounds that can curb aging by regulating senescent cells. Two of these drugs that have gained mainstay research traction are rapamycin and metformin.
Rapamycin
Originally extracted from bacteria found on Easter Island, Rapamycin acts on the m-TOR (mechanistic target of rapamycin) pathway to selectively block a key protein that facilitates cell division.
Currently, rapamycin derivatives are widely used as immunosuppression in organ and bone marrow transplants. Research now suggests that use results in prolonged lifespan and enhanced cognitive and immune function.
PureTech Health subsidiary resTORbio (which started 2018 by going public) is working on a rapamycin-based drug intended to enhance immunity and reduce infection. Their clinical-stage RTB101 drug works by inhibiting part of the mTOR pathway.
Results of the drug’s recent clinical trial include:
Decreased incidence of infection
Improved influenza vaccination response
A 30.6 percent decrease in respiratory tract infections
Impressive, to say the least.
Metformin
Metformin is a widely-used generic drug for mitigating liver sugar production in Type 2 diabetes patients.
Researchers have found that Metformin also reduces oxidative stress and inflammation, which otherwise increase as we age.
There is strong evidence that Metformin can augment cellular regeneration and dramatically mitigate cellular senescence by reducing both oxidative stress and inflammation.
Over 100 studies registered on ClinicalTrials.gov are currently following up on strong evidence of Metformin’s protective effect against cancer.
Nutraceuticals and NAD+
Beyond cellular senescence, certain critical nutrients and proteins tend to decline as a function of age. Nutraceuticals combat aging by supplementing and replenishing these declining nutrient levels.
NAD+ exists in every cell, participating in every process from DNA repair to creating the energy vital for cellular processes. It’s been shown that NAD+ levels decline as we age.
The Elysium Health Basis supplement aims to elevate NAD+ levels in the body to extend one’s lifespan. Elysium’s clinical study reports that Basis increases NAD+ levels consistently by a sustained 40 percent.
Conclusion
These are just a taste of the tremendous momentum that longevity and aging technology has right now. As artificial intelligence and quantum computing transform how we decode our DNA and how we discover drugs, genetics and pharmaceuticals will become truly personalized.
The next blog in this series will demonstrate how artificial intelligence is converging with genetics and pharmaceuticals to transform how we approach longevity, aging, and vitality.
We are edging closer to a dramatically extended healthspan—where 100 is the new 60. What will you create, where will you explore, and how will you spend your time if you are able to add an additional 40 healthy years to your life?
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Posted in Human Robots
#434559 Can AI Tell the Difference Between a ...
Scarcely a day goes by without another headline about neural networks: some new task that deep learning algorithms can excel at, approaching or even surpassing human competence. As the application of this approach to computer vision has continued to improve, with algorithms capable of specialized recognition tasks like those found in medicine, the software is getting closer to widespread commercial use—for example, in self-driving cars. Our ability to recognize patterns is a huge part of human intelligence: if this can be done faster by machines, the consequences will be profound.
Yet, as ever with algorithms, there are deep concerns about their reliability, especially when we don’t know precisely how they work. State-of-the-art neural networks will confidently—and incorrectly—classify images that look like television static or abstract art as real-world objects like school-buses or armadillos. Specific algorithms could be targeted by “adversarial examples,” where adding an imperceptible amount of noise to an image can cause an algorithm to completely mistake one object for another. Machine learning experts enjoy constructing these images to trick advanced software, but if a self-driving car could be fooled by a few stickers, it might not be so fun for the passengers.
These difficulties are hard to smooth out in large part because we don’t have a great intuition for how these neural networks “see” and “recognize” objects. The main insight analyzing a trained network itself can give us is a series of statistical weights, associating certain groups of points with certain objects: this can be very difficult to interpret.
Now, new research from UCLA, published in the journal PLOS Computational Biology, is testing neural networks to understand the limits of their vision and the differences between computer vision and human vision. Nicholas Baker, Hongjing Lu, and Philip J. Kellman of UCLA, alongside Gennady Erlikhman of the University of Nevada, tested a deep convolutional neural network called VGG-19. This is state-of-the-art technology that is already outperforming humans on standardized tests like the ImageNet Large Scale Visual Recognition Challenge.
They found that, while humans tend to classify objects based on their overall (global) shape, deep neural networks are far more sensitive to the textures of objects, including local color gradients and the distribution of points on the object. This result helps explain why neural networks in image recognition make mistakes that no human ever would—and could allow for better designs in the future.
In the first experiment, a neural network was trained to sort images into 1 of 1,000 different categories. It was then presented with silhouettes of these images: all of the local information was lost, while only the outline of the object remained. Ordinarily, the trained neural net was capable of recognizing these objects, assigning more than 90% probability to the correct classification. Studying silhouettes, this dropped to 10%. While human observers could nearly always produce correct shape labels, the neural networks appeared almost insensitive to the overall shape of the images. On average, the correct object was ranked as the 209th most likely solution by the neural network, even though the overall shapes were an exact match.
A particularly striking example arose when they tried to get the neural networks to classify glass figurines of objects they could already recognize. While you or I might find it easy to identify a glass model of an otter or a polar bear, the neural network classified them as “oxygen mask” and “can opener” respectively. By presenting glass figurines, where the texture information that neural networks relied on for classifying objects is lost, the neural network was unable to recognize the objects by shape alone. The neural network was similarly hopeless at classifying objects based on drawings of their outline.
If you got one of these right, you’re better than state-of-the-art image recognition software. Image Credit: Nicholas Baker, Hongjing Lu, Gennady Erlikhman, Philip J. Kelman. “Deep convolutional networks do not classify based on global object shape.” Plos Computational Biology. 12/7/18. / CC BY 4.0
When the neural network was explicitly trained to recognize object silhouettes—given no information in the training data aside from the object outlines—the researchers found that slight distortions or “ripples” to the contour of the image were again enough to fool the AI, while humans paid them no mind.
The fact that neural networks seem to be insensitive to the overall shape of an object—relying instead on statistical similarities between local distributions of points—suggests a further experiment. What if you scrambled the images so that the overall shape was lost but local features were preserved? It turns out that the neural networks are far better and faster at recognizing scrambled versions of objects than outlines, even when humans struggle. Students could classify only 37% of the scrambled objects, while the neural network succeeded 83% of the time.
Humans vastly outperform machines at classifying object (a) as a bear, while the machine learning algorithm has few problems classifying the bear in figure (b). Image Credit: Nicholas Baker, Hongjing Lu, Gennady Erlikhman, Philip J. Kelman. “Deep convolutional networks do not classify based on global object shape.” Plos Computational Biology. 12/7/18. / CC BY 4.0
“This study shows these systems get the right answer in the images they were trained on without considering shape,” Kellman said. “For humans, overall shape is primary for object recognition, and identifying images by overall shape doesn’t seem to be in these deep learning systems at all.”
Naively, one might expect that—as the many layers of a neural network are modeled on connections between neurons in the brain and resemble the visual cortex specifically—the way computer vision operates must necessarily be similar to human vision. But this kind of research shows that, while the fundamental architecture might resemble that of the human brain, the resulting “mind” operates very differently.
Researchers can, increasingly, observe how the “neurons” in neural networks light up when exposed to stimuli and compare it to how biological systems respond to the same stimuli. Perhaps someday it might be possible to use these comparisons to understand how neural networks are “thinking” and how those responses differ from humans.
But, as yet, it takes a more experimental psychology to probe how neural networks and artificial intelligence algorithms perceive the world. The tests employed against the neural network are closer to how scientists might try to understand the senses of an animal or the developing brain of a young child rather than a piece of software.
By combining this experimental psychology with new neural network designs or error-correction techniques, it may be possible to make them even more reliable. Yet this research illustrates just how much we still don’t understand about the algorithms we’re creating and using: how they tick, how they make decisions, and how they’re different from us. As they play an ever-greater role in society, understanding the psychology of neural networks will be crucial if we want to use them wisely and effectively—and not end up missing the woods for the trees.
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