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The causes of aging are extremely complex and unclear. But with longevity clinical trials increasing, more answers—and questions—are emerging than ever before.
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 turn those answers into practical ways to extend our healthspan.
In this article, I’ll explore how genome sequencing and editing, along with new classes of anti-aging drugs, are augmenting our biology to further extend our healthy lives.
Genome Sequencing and 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 for 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 $1,500 in 2015.
Today, the cost of genome sequencing has dropped below $600, 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 article).
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 have used CRISPR to genetically engineer cocaine resistance into mice, reverse the gene defect causing Duchenne muscular dystrophy (DMD) in dogs, and reduce genetic deafness in mice.
Already this year, CRISPR-edited immune cells have been shown to successfully kill cancer cells in human patients. Researchers have discovered ways to activate CRISPR with light and use the gene-editing technology to better understand Alzheimer’s disease progression.
With great power comes great responsibility, and the opportunity for 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. Because Jiankui forged ethical review documents and misled doctors in the process, he was sentenced to three years in prison and fined $429,000 last December.
Coupled with significant ethical conversations necessary for progress, 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, and 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 Biotechnologies is pioneering a programmable gene therapy that can destroy cells based on their internal biochemistry.
SIWA Therapeutics is 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.
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 for 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 went public in 2018) 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, and a 30.6 percent decrease in respiratory tract infection.
Impressive, to say the least.
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.
(3) 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 first clinical study reports that Basis increases NAD+ levels consistently by a sustained 40 percent.
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 article 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 toward 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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(2) Abundance-Digital Online Community: I’ve also created a Digital/Online community of bold, abundance-minded entrepreneurs called Abundance-Digital. Abundance-Digital is Singularity University’s ‘onramp’ for exponential entrepreneurs—those who want to get involved and play at a higher level. Click here to learn more.
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This article originally appeared on diamandis.com. Read the original article here.
Image Credit: Arek Socha from Pixabay Continue reading
Why the Coronavirus Is So Confusing
Ed Yong | The Atlantic
“…beyond its vast scope and sui generis nature, there are other reasons the pandemic continues to be so befuddling—a slew of forces scientific and societal, epidemiological and epistemological. What follows is an analysis of those forces, and a guide to making sense of a problem that is now too big for any one person to fully comprehend.”
Common Sense Comes Closer to Computers
John Pavlus | Quanta Magazine
“The problem of common-sense reasoning has plagued the field of artificial intelligence for over 50 years. Now a new approach, borrowing from two disparate lines of thinking, has made important progress.”
Scientists Create Glowing Plants Using Bioluminescent Mushroom DNA
George Dvorsky | Gizmodo
“New research published today in Nature Biotechnology describes a new technique, in which the DNA from bioluminescent mushrooms was used to create plants that glow 10 times brighter than their bacteria-powered precursors. Botanists could eventually use this technique to study the inner workings of plants, but it also introduces the possibility of glowing ornamental plants for our homes.”
Old Drugs May Find a New Purpose: Fighting the Coronavirus
Carl Zimmer | The New York Times
“Driven by the pandemic’s spread, research teams have been screening thousands of drugs to see if they have this unexpected potential to fight the coronavirus. They’ve tested the drugs on dishes of cells, and a few dozen candidates have made the first cut.”
OpenAI’s New Experiments in Music Generation Create an Uncanny Valley Elvis
Devin Coldewey | TechCrunch
“AI-generated music is a fascinating new field, and deep-pocketed research outfit OpenAI has hit new heights in it, creating recreations of songs in the style of Elvis, 2Pac and others. The results are convincing, but fall squarely in the unnerving ‘uncanny valley’ of audio, sounding rather like good, but drunk, karaoke heard through a haze of drugs.”
Neural Net-Generated Memes Are One of the Best Uses of AI on the Internet
Jay Peters | The Verge
“I’ve spent a good chunk of my workday so far creating memes thanks to this amazing website from Imgflip that automatically generates captions for memes using a neural network. …You can pick from 48 classic meme templates, including distracted boyfriend, Drake in ‘Hotline Bling,’ mocking Spongebob, surprised Pikachu, and Oprah giving things away.”
Can Genetic Engineering Bring Back the American Chestnut?
Gabriel Popkin | The New York Times Magazine
“The geneticists’ research forces conservationists to confront, in a new and sometimes discomfiting way, the prospect that repairing the natural world does not necessarily mean returning to an unblemished Eden. It may instead mean embracing a role that we’ve already assumed: engineers of everything, including nature.”
Image credit: Dan Gold / Unsplash Continue reading
When you imagine an exoskeleton, chances are it might look a bit like the Guardian XO from Sarcos Robotics. The XO is literally a robot you wear (or maybe, it wears you). The suit’s powered limbs sense your movements and match their position to yours with little latency to give you effortless superstrength and endurance—lifting 200 pounds will feel like 10.
A vision of robots and humankind working together in harmony. Now, isn’t that nice?
Of course, there isn’t anything terribly novel about an exoskeleton. We’ve seen plenty of concepts and demonstrations in the last decade. These include light exoskeletons tailored to industrial settings—some of which are being tested out by the likes of Honda—and healthcare exoskeletons that support the elderly or folks with disabilities.
Full-body powered robotic exoskeletons are a bit rarer, which makes the Sarcos suit pretty cool to look at. But like all things in robotics, practicality matters as much as vision. It’s worth asking: Will anyone buy and use the thing? Is it more than a concept video?
Sarcos thinks so, and they’re excited about it. “If you were to ask the question, what does 30 years and $300 million look like,” Sarcos CEO, Ben Wolff, told IEEE Spectrum, “you’re going to see it downstairs.”
The XO appears to check a few key boxes. For one, it’s user friendly. According to Sarcos, it only takes a few minutes for the uninitiated to strap in and get up to speed. Feeling comfortable doing work with the suit takes a few hours. This is thanks to a high degree of sensor-based automation that allows the robot to seamlessly match its user’s movements.
The XO can also operate for more than a few minutes. It has two hours of battery life, and with spares on hand, it can go all day. The batteries are hot-swappable, meaning you can replace a drained battery with a new one without shutting the system down.
The suit is aimed at manufacturing, where workers are regularly moving heavy stuff around. Additionally, Wolff told CNET, the suit could see military use. But that doesn’t mean Avatar-style combat. The XO, Wolff said, is primarily about logistics (lifting and moving heavy loads) and isn’t designed to be armored, so it won’t likely see the front lines.
The system will set customers back $100,000 a year to rent, which sounds like a lot, but for industrial or military purposes, the six-figure rental may not deter would-be customers if the suit proves itself a useful bit of equipment. (And it’s reasonable to imagine the price coming down as the technology becomes more commonplace and competitors arrive.)
Sarcos got into exoskeletons a couple decades ago and was originally funded by the military (like many robotics endeavors). Videos hit YouTube as long ago as 2008, but after announcing the company was taking orders for the XO earlier this year, Sarcos says they’ll deliver the first alpha units in January, which is a notable milestone.
Broadly, robotics has advanced a lot in recent years. YouTube sensations like Boston Dynamics have regularly earned millions of views (and inevitably, headlines stoking robot fear). They went from tethered treadmill sessions to untethered backflips off boxes. While today’s robots really are vastly superior to their ancestors, they’ve struggled to prove themselves useful. A counterpoint to flashy YouTube videos, the DARPA Robotics Challenge gave birth to another meme altogether. Robots falling over. Often and awkwardly.
This year marks some of the first commercial fruits of a few decades’ research. Boston Dynamics recently started offering its robot dog, Spot, to select customers in 2019. Whether this proves to be a headline-worthy flash in the pan or something sustainable remains to be seen. But between robots with more autonomy and exoskeletons like the XO, the exoskeleton variety will likely be easier to make more practical for various uses.
Whereas autonomous robots require highly advanced automation to navigate uncertain and ever-changing conditions—automation which, at the moment, remains largely elusive (though the likes of Google are pairing the latest AI with robots to tackle the problem)—an exoskeleton mainly requires physical automation. The really hard bits, like navigating and recognizing and interacting with objects, are outsourced to its human operator.
As it turns out, for today’s robots the best AI is still us. We may yet get chipper automatons like Rosy the Robot, but until then, for complicated applications, we’ll strap into our mechs for their strength and endurance, and they’ll wear us for our brains.
Image Credit: Sarcos Robotics Continue reading