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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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When we think of wisdom, we often think of ancient philosophers, mystics, or spiritual leaders. Wisdom is associated with the past. Yet some intellectual leaders are challenging us to reconsider wisdom in the context of the technological evolution of the future.
With the rise of exponential technologies like virtual reality, big data, artificial intelligence, and robotics, people are gaining access to increasingly powerful tools. These tools are neither malevolent nor benevolent on their own; human values and decision-making influence how they are used.
In future-themed discussions we often focus on technological progress far more than on intellectual and moral advancements. In reality, the virtuous insights that future humans possess will be even more powerful than their technological tools.
Tom Lombardo and Ray Todd Blackwood are advocating for exactly this. In their interdisciplinary paper “Educating the Wise Cyborg of the Future,” they propose a new definition of wisdom—one that is relevant in the context of the future of humanity.
We Are Already Cyborgs
The core purpose of Lombardo and Blackwood’s paper is to explore revolutionary educational models that will prepare humans, soon-to-be-cyborgs, for the future. The idea of educating such “cyborgs” may sound like science fiction, but if you pay attention to yourself and the world around you, cyborgs came into being a long time ago.
Techno-philosophers like Jason Silva point out that our tech devices are an abstract form of brain-machine interfaces. We use smartphones to store and retrieve information, perform calculations, and communicate with each other. Our devices are an extension of our minds.
According to philosophers Andy Clark and David Chalmers’ theory of the extended mind, we use this technology to expand the boundaries of our minds. We use tools like machine learning to enhance our cognitive skills or powerful telescopes to enhance our visual reach. Such is how technology has become a part of our exoskeletons, allowing us to push beyond our biological limitations.
In other words, you are already a cyborg. You have been all along.
Such an abstract definition of cyborgs is both relevant and thought-provoking. But it won’t stay abstract for much longer. The past few years have seen remarkable developments in both the hardware and software of brain-machine interfaces. Experts are designing more intricate electrodes while programming better algorithms to interpret the neural signals. Scientists have already succeeded in enabling paralyzed patients to type with their minds, and are even allowing people to communicate purely through brainwaves. Technologists like Ray Kurzweil believe that by 2030 we will connect the neocortex of our brains to the cloud via nanobots.
Given these trends, humans will continue to be increasingly cyborg-like. Our future schools may not necessarily educate people as we are today, but rather will be educating a new species of human-machine hybrid.
Whether you take an abstract or literal definition of a cyborg, we need to completely revamp our educational models. Even if you don’t buy into the scenario where humans integrate powerful brain-machine interfaces into our minds, there is still a desperate need for wisdom-based education to equip current generations to tackle 21st-century issues.
With an emphasis on isolated subjects, standardized assessments, and content knowledge, our current educational models were designed for the industrial era, with the intended goal of creating masses of efficient factory workers—not to empower critical thinkers, innovators, or wise cyborgs.
Currently, the goal of higher education is to provide students with the degree that society tells them they need, and ostensibly to prepare them for the workforce. In contrast, Lombardo and Blackwood argue that wisdom should be the central goal of higher education, and they elaborate on how we can practically make this happen. Lombardo has developed a comprehensive two-year foundational education program for incoming university students aimed at the development of wisdom.
What does such an educational model look like? Lombardo and Blackwood break wisdom down into individual traits and capacities, each of which can be developed and measured independently or in combination with others. The authors lay out an expansive list of traits that can influence our decision-making as we strive to tackle global challenges and pave a more exciting future. These include big-picture thinking, curiosity, wonder, compassion, self-transcendence, love of learning, optimism, and courage.
As the authors point out, “given the complex and transforming nature of the world we live in, the development of wisdom provides a holistic, perspicacious, and ethically informed foundation for understanding the world, identifying its critical problems and positive opportunities, and constructively addressing its challenges.”
After all, many of the challenges we see in our world today boil down to out-dated ways of thinking, be they regressive mindsets, superficial value systems, or egocentric mindsets. The development of wisdom would immunize future societies against such debilitating values; imagine what our world would be like if wisdom was ingrained in all leaders and participating members of society.
The Wise Cyborg
Lombardo and Blackwood invite us to imagine how the wise cyborgs of the future would live their lives. What would happen if the powerful human-machine hybrids of tomorrow were also purpose-driven, compassionate, and ethical?
They would perceive the evolving digital world through a lens of wonder, awe, and curiosity. They would use digital information as a tool for problem-solving and a source of infinite knowledge. They would leverage immersive mediums like virtual reality to enhance creative expression and experimentation. They would continue to adapt and thrive in an unpredictable world of accelerating change.
Our media often depict a dystopian future for our species. It is worth considering a radically positive yet plausible scenario where instead of the machines taking over, we converge with them into wise cyborgs. This is just a glimpse of what is possible if we combine transcendent wisdom with powerful exponential technologies.
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