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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.
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 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.
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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Image Credit: ktsdesign / Shutterstock.com Continue reading
We all have scars, and each one tells a story. Tales of tomfoolery, tales of haphazardness, or in my case, tales of stupidity.
Whether the cause of your scar was a push-bike accident, a lack of concentration while cutting onions, or simply the byproduct of an active lifestyle, the experience was likely extremely painful and distressing. Not to mention the long and vexatious recovery period, stretching out for weeks and months after the actual event!
Cast your minds back to that time. How you longed for instant relief from your discomfort! How you longed to have your capabilities restored in an instant!
Well, materials that can heal themselves in an instant may not be far from becoming a reality—and a family of them known as elastomers holds the key.
“Elastomer” is essentially a big, fancy word for rubber. However, elastomers have one unique property—they are capable of returning to their original form after being vigorously stretched and deformed.
This unique property of elastomers has caught the eye of many scientists around the world, particularly those working in the field of robotics. The reason? Elastomer can be encouraged to return to its original shape, in many cases by simply applying heat. The implication of this is the quick and cost-effective repair of “wounds”—cuts, tears, and punctures to the soft, elastomer-based appendages of a robot’s exoskeleton.
Researchers from Vrije University in Brussels, Belgium have been toying with the technique, and with remarkable success. The team built a robotic hand with fingers made of a type of elastomer. They found that cuts and punctures were indeed able to repair themselves simply by applying heat to the affected area.
How long does the healing process take? In this instance, about a day. Now that’s a lot shorter than the weeks and months of recovery time we typically need for a flesh wound, during which we are unable to write, play the guitar, or do the dishes. If you consider the latter to be a bad thing…
However, it’s not the first time scientists have played around with elastomers and examined their self-healing properties. Another team of scientists, headed up by Cheng-Hui Li and Chao Wang, discovered another type of elastomer that exhibited autonomous self-healing properties. Just to help you picture this stuff, the material closely resembles animal muscle— strong, flexible, and elastic. With autogenetic restorative powers to boot.
Advancements in the world of self-healing elastomers, or rubbers, may also affect the lives of everyday motorists. Researchers from the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) have developed a self-healing rubber material that could be used to make tires that repair their own punctures.
This time the mechanism of self-healing doesn’t involve heat. Rather, it is related to a physical phenomenon associated with the rubber’s unique structure. Normally, when a large enough stress is applied to a typical rubber, there is catastrophic failure at the focal point of that stress. The self-healing rubber the researchers created, on the other hand, distributes that same stress evenly over a network of “crazes”—which are like cracks connected by strands of fiber.
Here’s the interesting part. Not only does this unique physical characteristic of the rubber prevent catastrophic failure, it facilitates self-repair. According to Harvard researchers, when the stress is released, the material snaps back to its original form and the crazes heal.
This wonder material could be used in any number of rubber-based products.
Professor Jinrong Wu, of Sichuan University, China, and co-author of the study, happened to single out tires: “Imagine that we could use this material as one of the components to make a rubber tire… If you have a cut through the tire, this tire wouldn’t have to be replaced right away. Instead, it would self-heal while driving, enough to give you leeway to avoid dramatic damage,” said Wu.
So where to from here? Well, self-healing elastomers could have a number of different applications. According to the article published by Quartz, cited earlier, the material could be used on artificial limbs. Perhaps it will provide some measure of structural integrity without looking like a tattered mess after years of regular use.
Or perhaps a sort of elastomer-based hybrid skin is on the horizon. A skin in which wounds heal instantly. And recovery time, unlike your regular old human skin of yesteryear, is significantly slashed. Furthermore, this future skin might eliminate those little reminders we call scars.
For those with poor judgment skills, this spells an end to disquieting reminders of our own stupidity.
Image Credit: Vrije Universiteit Brussel / Prof. Dr. ir. Bram Vanderborght Continue reading