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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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This article originally appeared on diamandis.com. Read the original article here.
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A team of researchers from the University of California San Diego and the University of Science and Technology Beijing has developed a way to engineer platelets to propel themselves through biofluids as a means of delivering drugs to targeted parts of the body. In their paper published in the journal Science Robotics, the group outlines their method and how well it worked when tested in the lab. In the same issue, Jinjun Shi with Brigham and Women's Hospital has published a Focus piece outlining ongoing research into the development of natural drug delivery systems and the method used in this new effort. Continue reading
Creativity is a trait that makes humans unique from other species. We alone have the ability to make music and art that speak to our experiences or illuminate truths about our world. But suddenly, humans’ artistic abilities have some competition—and from a decidedly non-human source.
Over the last couple years there have been some remarkable examples of art produced by deep learning algorithms. They have challenged the notion of an elusive definition of creativity and put into perspective how professionals can use artificial intelligence to enhance their abilities and produce beyond the known boundaries.
But when creativity is the result of code written by a programmer, using a format given by a software engineer, featuring private and public datasets, how do we assign ownership of AI-generated content, and particularly that of artwork? McKinsey estimates AI will annually generate value of $3.5 to $5.8 trillion across various sectors.
In 2018, a portrait that was christened Edmond de Belamy was made in a French art collective called Obvious. It used a database with 15,000 portraits from the 1300s to the 1900s to train a deep learning algorithm to produce a unique portrait. The painting sold for $432,500 in a New York auction. Similarly, a program called Aiva, trained on thousands of classical compositions, has released albums whose pieces are being used by ad agencies and movies.
The datasets used by these algorithms were different, but behind both there was a programmer who changed the brush strokes or musical notes into lines of code and a data scientist or engineer who fitted and “curated” the datasets to use for the model. There could also have been user-based input, and the output may be biased towards certain styles or unintentionally infringe on similar pieces of art. This shows that there are many collaborators with distinct roles in producing AI-generated content, and it’s important to discuss how they can protect their proprietary interests.
A perspective article published in Nature Machine Intelligence by Jason K. Eshraghian in March looks into how AI artists and the collaborators involved should assess their ownership, laying out some guiding principles that are “only applicable for as long as AI does not have legal parenthood, the way humans and corporations are accorded.”
Before looking at how collaborators can protect their interests, it’s useful to understand the basic requirements of copyright law. The artwork in question must be an “original work of authorship fixed in a tangible medium.” Given this principle, the author asked whether it’s possible for AI to exercise creativity, skill, or any other indicator of originality. The answer is still straightforward—no—or at least not yet. Currently, AI’s range of creativity doesn’t exceed the standard used by the US Copyright Office, which states that copyright law protects the “fruits of intellectual labor founded in the creative powers of the mind.”
Due to the current limitations of narrow AI, it must have some form of initial input that helps develop its ability to create. At the moment AI is a tool that can be used to produce creative work in the same way that a video camera is a tool used to film creative content. Video producers don’t need to comprehend the inner workings of their cameras; as long as their content shows creativity and originality, they have a proprietary claim over their creations.
The same concept applies to programmers developing a neural network. As long as the dataset they use as input yields an original and creative result, it will be protected by copyright law; they don’t need to understand the high-level mathematics, which in this case are often black box algorithms whose output it’s impossible to analyze.
Will robots and algorithms eventually be treated as creative sources able to own copyrights? The author pointed to the recent patent case of Warner-Lambert Co Ltd versus Generics where Lord Briggs, Justice of the Supreme Court of the UK, determined that “the court is well versed in identifying the governing mind of a corporation and, when the need arises, will no doubt be able to do the same for robots.”
In the meantime, Dr. Eshraghian suggests four guiding principles to allow artists who collaborate with AI to protect themselves.
First, programmers need to document their process through online code repositories like GitHub or BitBucket.
Second, data engineers should also document and catalog their datasets and the process they used to curate their models, indicating selectivity in their criteria as much as possible to demonstrate their involvement and creativity.
Third, in cases where user data is utilized, the engineer should “catalog all runs of the program” to distinguish the data selection process. This could be interpreted as a way of determining whether user-based input has a right to claim the copyright too.
Finally, the output should avoid infringing on others’ content through methods like reverse image searches and version control, as mentioned above.
AI-generated artwork is still a very new concept, and the ambiguous copyright laws around it give a lot of flexibility to AI artists and programmers worldwide. The guiding principles Eshraghian lays out will hopefully shed some light on the legislation we’ll eventually need for this kind of art, and start an important conversation between all the stakeholders involved.
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Electricity plays a surprisingly powerful role in our bodies. While most people are aware that it plays a crucial role in carrying signals to and from our nerves, our bodies produce electric fields that can do everything from helping heal wounds to triggering the release of hormones.
Electric fields can influence a host of important cellular behavior, like directional migration, proliferation, division, or even differentiation into different cell types. The work of Michael Levin at Tufts University even suggests that electrical fields may play a crucial role in the way our bodies organize themselves.
This has prompted considerable interest in exploiting our body’s receptiveness to electrical stimulation for therapeutic means, but given the diffuse nature of electrical fields a key challenge is finding a way to localize these effects. Conductive polymers have proven a useful tool in this regard thanks to their good electrical properties and biocompatibility, and have been used in everything from neural implants to biosensors.
But now, a team at Stanford University has developed a way to genetically engineer neurons to build the materials into their own cell membranes. The approach could make it possible to target highly specific groups of cells, providing unprecedented control over the body’s response to electrical stimulation.
In a paper in Science, the team explained how they used re-engineered viruses to deliver DNA that hijacks cells’ biosynthesis machinery to create an enzyme that assembles electroactive polymers onto their membranes. This changes the electrical properties of the cells, which the team demonstrated could be used to control their behavior.
They used the approach to modulate neuronal firing in cultures of rat hippocampal neurons, mouse brain slices, and even human cortical spheroids. Most impressively, they showed that they could coax the neurons of living C. elegans worms to produce the polymers in large enough quantities to alter their behavior without impairing the cells’ natural function.
Translating the idea to humans poses major challenges, not least because the viruses used to deliver the genetic changes are still a long way from being approved for clinical use. But the ability to precisely target specific cells using a genetic approach holds enormous promise for bioelectronic medicine, Kevin Otto and Christine Schmidt from the University of Florida say in an accompanying perspective.
Interest is booming in therapies that use electrical stimulation of neural circuits as an alternative to drugs for diseases as varied as arthritis, Alzheimer’s, diabetes, and cardiovascular disease, and hundreds of clinical trials are currently underway.
At present these approaches rely on electrodes that can provide some level of localization, but because different kinds of nerve cells are often packed closely together it’s proven hard to stimulate exactly the right nerves, say Otto and Schmidt. This new approach makes it possible to boost the conductivity of specific cell types, which could make these kinds of interventions dramatically more targeted.
Besides disease-focused bioelectronic interventions, Otto and Schmidt say the approach could prove invaluable for helping to interface advanced prosthetics with patients’ nervous systems by making it possible to excite sensory neurons without accidentally triggering motor neurons, or vice versa.
More speculatively, the approach could one day help create far more efficient bridges between our minds and machines. One of the major challenges for brain-machine interfaces is recording from specific neurons, something that a genetically targeted approach might be able to help greatly with.
If the researchers can replicate the ability to build electronic-tissue “composites” in humans, we may be well on our way to the cyborg future predicted by science fiction.
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