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#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

#434508 The Top Biotech and Medicine Advances to ...

2018 was bonkers for science.

From a woman who gave birth using a transplanted uterus, to the infamous CRISPR baby scandal, to forensics adopting consumer-based genealogy test kits to track down criminals, last year was a factory churning out scientific “whoa” stories with consequences for years to come.

With CRISPR still in the headlines, Britain ready to bid Europe au revoir, and multiple scientific endeavors taking off, 2019 is shaping up to be just as tumultuous.

Here are the science and health stories that may blow up in the new year. But first, a note of caveat: predicting the future is tough. Forecasting is the lovechild between statistics and (a good deal of) intuition, and entire disciplines have been dedicated to the endeavor. But January is the perfect time to gaze into the crystal ball for wisps of insight into the year to come. Last year we predicted the widespread approval of gene therapy products—on the most part, we nailed it. This year we’re hedging our bets with multiple predictions.

Gene Drives Used in the Wild
The concept of gene drives scares many, for good reason. Gene drives are a step up in severity (and consequences) from CRISPR and other gene-editing tools. Even with germline editing, in which the sperm, egg, or embryos are altered, gene editing affects just one genetic line—one family—at least at the beginning, before they reproduce with the general population.

Gene drives, on the other hand, have the power to wipe out entire species.

In a nutshell, they’re little bits of DNA code that help a gene transfer from parent to child with almost 100 percent perfect probability. The “half of your DNA comes from dad, the other comes from mom” dogma? Gene drives smash that to bits.

In other words, the only time one would consider using a gene drive is to change the genetic makeup of an entire population. It sounds like the plot of a supervillain movie, but scientists have been toying around with the idea of deploying the technology—first in mosquitoes, then (potentially) in rodents.

By releasing just a handful of mutant mosquitoes that carry gene drives for infertility, for example, scientists could potentially wipe out entire populations that carry infectious scourges like malaria, dengue, or Zika. The technology is so potent—and dangerous—the US Defense Advances Research Projects Agency is shelling out $65 million to suss out how to deploy, control, counter, or even reverse the effects of tampering with ecology.

Last year, the U.N. gave a cautious go-ahead for the technology to be deployed in the wild in limited terms. Now, the first release of a genetically modified mosquito is set for testing in Burkina Faso in Africa—the first-ever field experiment involving gene drives.

The experiment will only release mosquitoes in the Anopheles genus, which are the main culprits transferring disease. As a first step, over 10,000 male mosquitoes are set for release into the wild. These dudes are genetically sterile but do not cause infertility, and will help scientists examine how they survive and disperse as a preparation for deploying gene-drive-carrying mosquitoes.

Hot on the project’s heels, the nonprofit consortium Target Malaria, backed by the Bill and Melinda Gates foundation, is engineering a gene drive called Mosq that will spread infertility across the population or kill out all female insects. Their attempt to hack the rules of inheritance—and save millions in the process—is slated for 2024.

A Universal Flu Vaccine
People often brush off flu as a mere annoyance, but the infection kills hundreds of thousands each year based on the CDC’s statistical estimates.

The flu virus is actually as difficult of a nemesis as HIV—it mutates at an extremely rapid rate, making effective vaccines almost impossible to engineer on time. Scientists currently use data to forecast the strains that will likely explode into an epidemic and urge the public to vaccinate against those predictions. That’s partly why, on average, flu vaccines only have a success rate of roughly 50 percent—not much better than a coin toss.

Tired of relying on educated guesses, scientists have been chipping away at a universal flu vaccine that targets all strains—perhaps even those we haven’t yet identified. Often referred to as the “holy grail” in epidemiology, these vaccines try to alert our immune systems to parts of a flu virus that are least variable from strain to strain.

Last November, a first universal flu vaccine developed by BiondVax entered Phase 3 clinical trials, which means it’s already been proven safe and effective in a small numbers and is now being tested in a broader population. The vaccine doesn’t rely on dead viruses, which is a common technique. Rather, it uses a small chain of amino acids—the chemical components that make up proteins—to stimulate the immune system into high alert.

With the government pouring $160 million into the research and several other universal candidates entering clinical trials, universal flu vaccines may finally experience a breakthrough this year.

In-Body Gene Editing Shows Further Promise
CRISPR and other gene editing tools headed the news last year, including both downers suggesting we already have immunity to the technology and hopeful news of it getting ready for treating inherited muscle-wasting diseases.

But what wasn’t widely broadcasted was the in-body gene editing experiments that have been rolling out with gusto. Last September, Sangamo Therapeutics in Richmond, California revealed that they had injected gene-editing enzymes into a patient in an effort to correct a genetic deficit that prevents him from breaking down complex sugars.

The effort is markedly different than the better-known CAR-T therapy, which extracts cells from the body for genetic engineering before returning them to the hosts. Rather, Sangamo’s treatment directly injects viruses carrying the edited genes into the body. So far, the procedure looks to be safe, though at the time of reporting it was too early to determine effectiveness.

This year the company hopes to finally answer whether it really worked.

If successful, it means that devastating genetic disorders could potentially be treated with just a few injections. With a gamut of new and more precise CRISPR and other gene-editing tools in the works, the list of treatable inherited diseases is likely to grow. And with the CRISPR baby scandal potentially dampening efforts at germline editing via regulations, in-body gene editing will likely receive more attention if Sangamo’s results return positive.

Neuralink and Other Brain-Machine Interfaces
Neuralink is the stuff of sci fi: tiny implanted particles into the brain could link up your biological wetware with silicon hardware and the internet.

But that’s exactly what Elon Musk’s company, founded in 2016, seeks to develop: brain-machine interfaces that could tinker with your neural circuits in an effort to treat diseases or even enhance your abilities.

Last November, Musk broke his silence on the secretive company, suggesting that he may announce something “interesting” in a few months, that’s “better than anyone thinks is possible.”

Musk’s aspiration for achieving symbiosis with artificial intelligence isn’t the driving force for all brain-machine interfaces (BMIs). In the clinics, the main push is to rehabilitate patients—those who suffer from paralysis, memory loss, or other nerve damage.

2019 may be the year that BMIs and neuromodulators cut the cord in the clinics. These devices may finally work autonomously within a malfunctioning brain, applying electrical stimulation only when necessary to reduce side effects without requiring external monitoring. Or they could allow scientists to control brains with light without needing bulky optical fibers.

Cutting the cord is just the first step to fine-tuning neurological treatments—or enhancements—to the tune of your own brain, and 2019 will keep on bringing the music.

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Posted in Human Robots

#434235 The Milestones of Human Progress We ...

When you look back at 2018, do you see a good or a bad year? Chances are, your perception of the year involves fixating on all the global and personal challenges it brought. In fact, every year, we tend to look back at the previous year as “one of the most difficult” and hope that the following year is more exciting and fruitful.

But in the grander context of human history, 2018 was an extraordinarily positive year. In fact, every year has been getting progressively better.

Before we dive into some of the highlights of human progress from 2018, let’s make one thing clear. There is no doubt that there are many overwhelming global challenges facing our species. From climate change to growing wealth inequality, we are far from living in a utopia.

Yet it’s important to recognize that both our news outlets and audiences have been disproportionately fixated on negative news. This emphasis on bad news is detrimental to our sense of empowerment as a species.

So let’s take a break from all the disproportionate negativity and have a look back on how humanity pushed boundaries in 2018.

On Track to Becoming an Interplanetary Species
We often forget how far we’ve come since the very first humans left the African savanna, populated the entire planet, and developed powerful technological capabilities. Our desire to explore the unknown has shaped the course of human evolution and will continue to do so.

This year, we continued to push the boundaries of space exploration. As depicted in the enchanting short film Wanderers, humanity’s destiny is the stars. We are born to be wanderers of the cosmos and the everlasting unknown.

SpaceX had 21 successful launches in 2018 and closed the year with a successful GPS launch. The latest test flight by Virgin Galactic was also an incredible milestone, as SpaceShipTwo was welcomed into space. Richard Branson and his team expect that space tourism will be a reality within the next 18 months.

Our understanding of the cosmos is also moving forward with continuous breakthroughs in astrophysics and astronomy. One notable example is the MARS InSight Mission, which uses cutting-edge instruments to study Mars’ interior structure and has even given us the first recordings of sound on Mars.

Understanding and Tackling Disease
Thanks to advancements in science and medicine, we are currently living longer, healthier, and wealthier lives than at any other point in human history. In fact, for most of human history, life expectancy at birth was around 30. Today it is more than 70 worldwide, and in the developed parts of the world, more than 80.

Brilliant researchers around the world are pushing for even better health outcomes. This year, we saw promising treatments emerge against Alzheimers disease, rheumatoid arthritis, multiple scleroris, and even the flu.

The deadliest disease of them all, cancer, is also being tackled. According to the American Association of Cancer Research, 22 revolutionary treatments for cancer were approved in the last year, and the death rate in adults is also in decline. Advancements in immunotherapy, genetic engineering, stem cells, and nanotechnology are all powerful resources to tackle killer diseases.

Breakthrough Mental Health Therapy
While cleaner energy, access to education, and higher employment rates can improve quality of life, they do not guarantee happiness and inner peace. According to the World Economic Forum, mental health disorders affect one in four people globally, and in many places they are significantly under-reported. More people are beginning to realize that our mental health is just as important as our physical health, and that we ought to take care of our minds just as much as our bodies.

We are seeing the rise of applications that put mental well-being at their center. Breakthrough advancements in genetics are allowing us to better understand the genetic makeup of disorders like clinical depression or Schizophrenia, and paving the way for personalized medical treatment. We are also seeing the rise of increasingly effective therapeutic treatments for anxiety.

This year saw many milestones for a whole new revolutionary area in mental health: psychedelic therapy. Earlier this summer, the FDA granted breakthrough therapy designation to MDMA for the treatment of PTSD, after several phases of successful trails. Similar research has discovered that Psilocybin (also known as magic mushrooms) combined with therapy is far more effective than traditional forms of treatment for depression and anxiety.

Moral and Social Progress
Innovation is often associated with economic and technological progress. However, we also need leaps of progress in our morality, values, and policies. Throughout the 21st century, we’ve made massive strides in rights for women and children, civil rights, LGBT rights, animal rights, and beyond. However, with rising nationalism and xenophobia in many parts of the developed world, there is significant work to be done on this front.

All hope is not lost, as we saw many noteworthy milestones this year. In January 2018, Iceland introduced the equal wage law, bringing an end to the gender wage gap. On September 6th, the Indian Supreme Court decriminalized homosexuality, marking a historical moment. Earlier in December, the European Commission released a draft of ethics guidelines for trustworthy artificial intelligence. Such are just a few examples of positive progress in social justice, ethics, and policy.

We are also seeing a global rise in social impact entrepreneurship. Emerging startups are no longer valued simply based on their profits and revenue, but also on the level of positive impact they are having on the world at large. The world’s leading innovators are not asking themselves “How can I become rich?” but rather “How can I solve this global challenge?”

Intelligently Optimistic for 2019
It’s becoming more and more clear that we are living in the most exciting time in human history. Even more, we mustn’t be afraid to be optimistic about 2019.

An optimistic mindset can be grounded in rationality and evidence. Intelligent optimism is all about being excited about the future in an informed and rational way. The mindset is critical if we are to get everyone excited about the future by highlighting the rapid progress we have made and recognizing the tremendous potential humans have to find solutions to our problems.

In his latest TED talk, Steven Pinker points out, “Progress does not mean that everything becomes better for everyone everywhere all the time. That would be a miracle, and progress is not a miracle but problem-solving. Problems are inevitable and solutions create new problems which have to be solved in their turn.”

Let us not forget that in cosmic time scales, our entire species’ lifetime, including all of human history, is the equivalent of the blink of an eye. The probability of us existing both as an intelligent species and as individuals is so astoundingly low that it’s practically non-existent. We are the products of 14 billion years of cosmic evolution and extraordinarily good fortune. Let’s recognize and leverage this wondrous opportunity, and pave an exciting way forward.

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Posted in Human Robots

#433928 The Surprising Parallels Between ...

The human mind can be a confusing and overwhelming place. Despite incredible leaps in human progress, many of us still struggle to make our peace with our thoughts. The roots of this are complex and multifaceted. To find explanations for the global mental health epidemic, one can tap into neuroscience, psychology, evolutionary biology, or simply observe the meaningless systems that dominate our modern-day world.

This is not only the context of our reality but also that of the critically-acclaimed Netflix series, Maniac. Psychological dark comedy meets science fiction, Maniac is a retro, futuristic, and hallucinatory trip that is filled with hidden symbols. Directed by Cary Joji Fukunaga, the series tells the story of two strangers who decide to participate in the final stage of a “groundbreaking” pharmaceutical trial—one that combines novel pharmaceuticals with artificial intelligence, and promises to make their emotional pain go away.

Naturally, things don’t go according to plan.

From exams used for testing defense mechanisms to techniques such as cognitive behavioral therapy, the narrative infuses genuine psychological science. As perplexing as the series may be to some viewers, many of the tools depicted actually have a strong grounding in current technological advancements.

Catalysts for Alleviating Suffering
In the therapy of Maniac, participants undergo a three-day trial wherein they ingest three pills and appear to connect their consciousness to a superintelligent AI. Each participant is hurled into the traumatic experiences imprinted in their subconscious and forced to cope with them in a series of hallucinatory and dream-like experiences.

Perhaps the most recognizable parallel that can be drawn is with the latest advancements in psychedelic therapy. Psychedelics are a class of drugs that alter the experience of consciousness, and often cause radical changes in perception and cognitive processes.

Through a process known as transient hypofrontality, the executive “over-thinking” parts of our brains get a rest, and deeper areas become more active. This experience, combined with the breakdown of the ego, is often correlated with feelings of timelessness, peacefulness, presence, unity, and above all, transcendence.

Despite being not addictive and extremely difficult to overdose on, regulators looked down on the use of psychedelics for decades and many continue to dismiss them as “party drugs.” But in the last few years, all of this began to change.

Earlier this summer, the FDA granted breakthrough therapy designation to MDMA for the treatment of PTSD, after several phases of successful trails. Similar research has discovered that Psilocybin (also known as magic mushrooms) combined with therapy is far more effective than traditional forms of treatment to treat depression and anxiety. Today, there is a growing and overwhelming body of research that proves that not only are psychedelics such as LSD, MDMA, or Psylicybin effective catalysts to alleviate suffering and enhance the human condition, but they are potentially the most effective tools out there.

It’s important to realize that these substances are not solutions on their own, but rather catalysts for more effective therapy. They can be groundbreaking, but only in the right context and setting.

Brain-Machine Interfaces
In Maniac, the medication-assisted therapy is guided by what appears to be a super-intelligent form of artificial intelligence called the GRTA, nicknamed Gertie. Gertie, who is a “guide” in machine form, accesses the minds of the participants through what appears to be a futuristic brain-scanning technology and curates customized hallucinatory experiences with the goal of accelerating the healing process.

Such a powerful form of brain-scanning technology is not unheard of. Current levels of scanning technology are already allowing us to decipher dreams and connect three human brains, and are only growing exponentially. Though they are nowhere as advanced as Gertie (we have a long way to go before we get to this kind of general AI), we are also seeing early signs of AI therapy bots, chatbots that listen, think, and communicate with users like a therapist would.

The parallels between current advancements in mental health therapy and the methods in Maniac can be startling, and are a testament to how science fiction and the arts can be used to explore the existential implications of technology.

Not Necessarily a Dystopia
While there are many ingenious similarities between the technology in Maniac and the state of mental health therapy, it’s important to recognize the stark differences. Like many other blockbuster science fiction productions, Maniac tells a fundamentally dystopian tale.

The series tells the story of the 73rd iteration of a controversial drug trial, one that has experienced many failures and even led to various participants being braindead. The scientists appear to be evil, secretive, and driven by their own superficial agendas and deep unresolved emotional issues.

In contrast, clinicians and researchers are not only required to file an “investigational new drug application” with the FDA (and get approval) but also update the agency with safety and progress reports throughout the trial.

Furthermore, many of today’s researchers are driven by a strong desire to contribute to the well-being and progress of our species. Even more, the results of decades of research by organizations like MAPS have been exceptionally promising and aligned with positive values. While Maniac is entertaining and thought-provoking, viewers must not forget the positive potential of such advancements in mental health therapy.

Science, technology, and psychology aside, Maniac is a deep commentary on the human condition and the often disorienting states that pain us all. Within any human lifetime, suffering is inevitable. It is the disproportionate, debilitating, and unjust levels of suffering that we ought to tackle as a society. Ultimately, Maniac explores whether advancements in science and technology can help us live not a life devoid of suffering, but one where it is balanced with fulfillment.

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Posted in Human Robots

#432691 Is the Secret to Significantly Longer ...

Once upon a time, a powerful Sumerian king named Gilgamesh went on a quest, as such characters often do in these stories of myth and legend. Gilgamesh had witnessed the death of his best friend, Enkidu, and, fearing a similar fate, went in search of immortality. The great king failed to find the secret of eternal life but took solace that his deeds would live well beyond his mortal years.

Fast-forward four thousand years, give or take a century, and Gilgamesh (as famous as any B-list celebrity today, despite the passage of time) would probably be heartened to learn that many others have taken up his search for longevity. Today, though, instead of battling epic monsters and the machinations of fickle gods, those seeking to enhance and extend life are cutting-edge scientists and visionary entrepreneurs who are helping unlock the secrets of human biology.

Chief among them is Aubrey de Grey, a biomedical gerontologist who founded the SENS Research Foundation, a Silicon Valley-based research organization that seeks to advance the application of regenerative medicine to age-related diseases. SENS stands for Strategies for Engineered Negligible Senescence, a term coined by de Grey to describe a broad array (seven, to be precise) of medical interventions that attempt to repair or prevent different types of molecular and cellular damage that eventually lead to age-related diseases like cancer and Alzheimer’s.

Many of the strategies focus on senescent cells, which accumulate in tissues and organs as people age. Not quite dead, senescent cells stop dividing but are still metabolically active, spewing out all sorts of proteins and other molecules that can cause inflammation and other problems. In a young body, that’s usually not a problem (and probably part of general biological maintenance), as a healthy immune system can go to work to put out most fires.

However, as we age, senescent cells continue to accumulate, and at some point the immune system retires from fire watch. Welcome to old age.

Of Mice and Men
Researchers like de Grey believe that treating the cellular underpinnings of aging could not only prevent disease but significantly extend human lifespans. How long? Well, if you’re talking to de Grey, Biblical proportions—on the order of centuries.

De Grey says that science has made great strides toward that end in the last 15 years, such as the ability to copy mitochondrial DNA to the nucleus. Mitochondria serve as the power plant of the cell but are highly susceptible to mutations that lead to cellular degeneration. Copying the mitochondrial DNA into the nucleus would help protect it from damage.

Another achievement occurred about six years ago when scientists first figured out how to kill senescent cells. That discovery led to a spate of new experiments in mice indicating that removing these ticking-time-bomb cells prevented disease and even extended their lifespans. Now the anti-aging therapy is about to be tested in humans.

“As for the next few years, I think the stream of advances is likely to become a flood—once the first steps are made, things get progressively easier and faster,” de Grey tells Singularity Hub. “I think there’s a good chance that we will achieve really dramatic rejuvenation of mice within only six to eight years: maybe taking middle-aged mice and doubling their remaining lifespan, which is an order of magnitude more than can be done today.”

Not Horsing Around
Richard G.A. Faragher, a professor of biogerontology at the University of Brighton in the United Kingdom, recently made discoveries in the lab regarding the rejuvenation of senescent cells with chemical compounds found in foods like chocolate and red wine. He hopes to apply his findings to an animal model in the future—in this case,horses.

“We have been very fortunate in receiving some funding from an animal welfare charity to look at potential treatments for older horses,” he explains to Singularity Hub in an email. “I think this is a great idea. Many aspects of the physiology we are studying are common between horses and humans.”

What Faragher and his colleagues demonstrated in a paper published in BMC Cell Biology last year was that resveralogues, chemicals based on resveratrol, were able to reactivate a protein called a splicing factor that is involved in gene regulation. Within hours, the chemicals caused the cells to rejuvenate and start dividing like younger cells.

“If treatments work in our old pony systems, then I am sure they could be translated into clinical trials in humans,” Faragher says. “How long is purely a matter of money. Given suitable funding, I would hope to see a trial within five years.”

Show Them the Money
Faragher argues that the recent breakthroughs aren’t because a result of emerging technologies like artificial intelligence or the gene-editing tool CRISPR, but a paradigm shift in how scientists understand the underpinnings of cellular aging. Solving the “aging problem” isn’t a question of technology but of money, he says.

“Frankly, when AI and CRISPR have removed cystic fibrosis, Duchenne muscular dystrophy or Gaucher syndrome, I’ll be much more willing to hear tales of amazing progress. Go fix a single, highly penetrant genetic disease in the population using this flashy stuff and then we’ll talk,” he says. “My faith resides in the most potent technological development of all: money.”

De Grey is less flippant about the role that technology will play in the quest to defeat aging. AI, CRISPR, protein engineering, advances in stem cell therapies, and immune system engineering—all will have a part.

“There is not really anything distinctive about the ways in which these technologies will contribute,” he says. “What’s distinctive is that we will need all of these technologies, because there are so many different types of damage to repair and they each require different tricks.”

It’s in the Blood
A startup in the San Francisco Bay Area believes machines can play a big role in discovering the right combination of factors that lead to longer and healthier lives—and then develop drugs that exploit those findings.

BioAge Labs raised nearly $11 million last year for its machine learning platform that crunches big data sets to find blood factors, such as proteins or metabolites, that are tied to a person’s underlying biological age. The startup claims that these factors can predict how long a person will live.

“Our interest in this comes out of research into parabiosis, where joining the circulatory systems of old and young mice—so that they share the same blood—has been demonstrated to make old mice healthier and more robust,” Dr. Eric Morgen, chief medical officer at BioAge, tells Singularity Hub.

Based on that idea, he explains, it should be possible to alter those good or bad factors to produce a rejuvenating effect.

“Our main focus at BioAge is to identify these types of factors in our human cohort data, characterize the important molecular pathways they are involved in, and then drug those pathways,” he says. “This is a really hard problem, and we use machine learning to mine these complex datasets to determine which individual factors and molecular pathways best reflect biological age.”

Saving for the Future
Of course, there’s no telling when any of these anti-aging therapies will come to market. That’s why Forever Labs, a biotechnology startup out of Ann Arbor, Michigan, wants your stem cells now. The company offers a service to cryogenically freeze stem cells taken from bone marrow.

The theory behind the procedure, according to Forever Labs CEO Steven Clausnitzer, is based on research showing that stem cells may be a key component for repairing cellular damage. That’s because stem cells can develop into many different cell types and can divide endlessly to replenish other cells. Clausnitzer notes that there are upwards of a thousand clinical studies looking at using stem cells to treat age-related conditions such as cardiovascular disease.

However, stem cells come with their own expiration date, which usually coincides with the age that most people start experiencing serious health problems. Stem cells harvested from bone marrow at a younger age can potentially provide a therapeutic resource in the future.

“We believe strongly that by having access to your own best possible selves, you’re going to be well positioned to lead healthier, longer lives,” he tells Singularity Hub.

“There’s a compelling argument to be made that if you started to maintain the bone marrow population, the amount of nuclear cells in your bone marrow, and to re-up them so that they aren’t declining with age, it stands to reason that you could absolutely mitigate things like cardiovascular disease and stroke and Alzheimer’s,” he adds.

Clausnitzer notes that the stored stem cells can be used today in developing therapies to treat chronic conditions such as osteoarthritis. However, the more exciting prospect—and the reason he put his own 38-year-old stem cells on ice—is that he believes future stem cell therapies can help stave off the ravages of age-related disease.

“I can start reintroducing them not to treat age-related disease but to treat the decline in the stem-cell niche itself, so that I don’t ever get an age-related disease,” he says. “I don’t think that it equates to immortality, but it certainly is a step in that direction.”

Indecisive on Immortality
The societal implications of a longer-living human species are a guessing game at this point. We do know that by mid-century, the global population of those aged 65 and older will reach 1.6 billion, while those older than 80 will hit nearly 450 million, according to the National Academies of Science. If many of those people could enjoy healthy lives in their twilight years, an enormous medical cost could be avoided.

Faragher is certainly working toward a future where human health is ubiquitous. Human immortality is another question entirely.

“The longer lifespans become, the more heavily we may need to control birth rates and thus we may have fewer new minds. This could have a heavy ‘opportunity cost’ in terms of progress,” he says.

And does anyone truly want to live forever?

“There have been happy moments in my life but I have also suffered some traumatic disappointments. No [drug] will wash those experiences out of me,” Faragher says. “I no longer view my future with unqualified enthusiasm, and I do not think I am the only middle-aged man to feel that way. I don’t think it is an accident that so many ‘immortalists’ are young.

“They should be careful what they wish for.”

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