Unlocking the secrets of longevity, CRISPR, OSK genes, and ancient insights.
Imagine holding the keys to life itself, the power to not only slow down aging, but to potentially
reverse it. Cutting-edge technologies, age-old discoveries, and a dash of ancient mystery are
converging to reshape our understanding of longevity. Are we standing on the verge of a
new era where we can unlock the secrets of life extension? Welcome back to the Longevity
Pink podcast, brought to you by Longevity.pink. I'm your host, Jamie Briggs, and in today's
episode, we're diving deep into the fascinating world of gene editing, ancient bacteria, and
the tantalizing possibilities they hold for extending human life. A quick recap. In our last episode,
we explored the groundbreaking advances in longevity science, from rapamycin to the Yamanaka
factors. Today, we're taking it a step further. We'll unravel the mysteries of CRISPR technology,
delve into the OSK genes that could turn back our cellular clocks, and journey through history
to see how ancient discoveries might be influencing modern science. Today, we'll discover the remarkable
story of CRISPR and the visionary scientists behind it. An in-depth look at how CRISPR-D-Cas9 technology
works, the groundbreaking OSK treatment, and how it could revolutionize aging. What can go wrong if
people are irresponsible with life extension technologies, the discovery of rapamycin on
Easter Island and its history, the speculation section. CRISPR-D-Cas9, the gene editing revolution.
First, let's celebrate the remarkable scientists who brought CRISPR technology to the forefront.
In 2020, Dr. Jennifer Doudna and Dr. Emmanuel Charpentier were awarded the Nobel Prize in Chemistry
for their pioneering work in developing CRISPR-Cas9, a revolutionary gene editing tool. Their discovery
has been hailed as one of the most significant breakthroughs in the history of biology.
So, what exactly is CRISPR? At its core, CRISPR stands for Clustered Regulatory
Inter-Spaced Short Palindromic Repeats. It's a natural system used by bacteria to fend off
viruses. Scientists have harnessed this system to create a tool that can precisely edit genes
much more cheaply than the many hundreds of thousands of dollars it cost before 2020.
Here's how CRISPR-Cas9 works. Guide RNA, GNRA. Think of this as a GPS that leads the way to a specific
spot in the DNA. Cas9 protein. This is like a pair of molecular scissors that can cut DNA at the exact
location directed by the GNRA. When the DNA is cut, the cell's natural repair mechanisms kick in,
and by employing this repair process, scientists can add, remove, or change pieces of genetic material,
causing it to express something new or different. This allows for precise editing of genes in a way
that allows research to progress much more quickly because of the price. Cutting DNA isn't always
desirable. It can be risky. That's where CRISPR-D-Cas9 comes into play. The D stands for dead.
This version of the protein can bind to DNA without cutting it. Instead of editing the DNA,
DCas9 can just turn genes on or off. This is especially important for aging research.
Key genes known as OSK, short for OCT4, SOX2, and KLF4, are crucial for reversing cellular aging.
Activating OSK without cutting DNA reduces the risk of errors and unwanted mutations.
By using DCas9 or peptides to overexpress the OSK genes, scientists can cause rejuvenation.
Why not use regular Cas9 for aging reversal? Using the standard Cas9 to cut DNA is error-prone
and can exist the risk of tumors due to unintended mutations. For aging reversal, precision and safety
are paramount. Activating genes without making cuts and using the cell's natural repair process
provides a controlled way to rejuvenate cells without introducing new risks.
Delivering CRISPR treatments. Methods of administration.
Getting CRISPR tools into the cells is a critical challenge. The method of delivery can impact the
effectiveness of the treatment.
General versus targeted administration.
General administration means delivering CRISPR components through the whole body.
It's considered for treatments aiming to have widespread effects, like potentially extending
lifespan or rejuvenating multiple issues. By reaching many cells, general administration
could promote systemic benefits.
An example of a general administration is an injection.
Targeted administration delivers CRISPR components to specific tissues or cell types.
It's commonly used in studies to focus on particular areas affected by disease.
Targeted delivery allows researchers to observe the effects in a controlled environment,
reducing variables that could complicate results.
It doesn't mean aging reversal treatments won't work when generally administered.
It just provides clearer data on how the treatment works in specific contexts.
An example of a targeted treatment would be adeno-associated viruses, which are designed to infect specific
parts of the body and break into the cells carrying the CRISPR treatment.
Controlled conditions focusing on a specific area, like the eye, help scientists understand the
effects without interference from other bodily systems.
It minimizes potential side effects elsewhere in the body during the initial testing phases,
and ensures that enough of the treatment reaches the intended cells to observe a significant effect.
It's important to get the CRISPR treatment inside the cell membrane in order to treat the cells.
Here is a little more detail about the three main types of delivery for CRISPR treatments.
1. First, viral vectors.
Adeno-associated viruses, AAVs.
These are harmless viruses engineered to carry CRISPR components into cells.
They can be designed to target specific cell types.
For example, in studies aiming to restore vision, AAVs deliver OSK genes directly to retinal cells
to cure glaucoma.
2. Then there are non-viral methods.
Physical techniques.
Methods like electroporation use electrical pulses to open cell membranes,
allowing CRISPR components inside.
Chemical carriers.
Cell-penetrating peptides and other molecules can carry CRISPR tools into cells without using viruses.
Injection.
CRISPR treatments are sometimes injected either into the embryo or into the living body
to provide general treatments.
3.
And finally, nanoparticles.
Lipid nanoparticles, LNPs, tiny fat-based particles that can encapsulate CRISPR components,
protecting them as they travel to target cells.
Polymeric nanoparticles.
Made from biodegradable materials.
They can be tailored for controlled release and targeted delivery.
Continuous versus cyclic expression.
Another key aspect is how long the introduced genes stay active.
The following are patterns of administration proven to work when expressing the OSK genes.
Continuous expression.
The genes are active for an extended period.
In some mouse studies, continuous expression of OSK genes restored vision without adverse effects.
In a time period of a couple of months.
Cyclic expression.
The genes are turned on and off in cycles.
This can achieve benefits while reducing potential risks from prolonged gene activation.
There are a number of scientific papers listed on the featured studies page on our homepage
that support continuous expression or cyclic expression of OSK are both effective to cure glaucoma in mice.
Their vision was cured quickly and there were supposedly no ill effects from continuous expression of the OSK genes in the eye.
As we continue to unlock the secrets of our genes,
the possibilities for improving health and extending vitality are truly exciting.
The future holds immense promise and with each discovery,
we're one step closer to making aging a thing of the past.
The OSK genes.
Turning back the cellular clock.
Unpacking OSK.
The OSK genes are three of the four Yamanaka factors discovered by Dr. Shinya Yamanaka,
which can reprogram mature cells back to a pluripotent stem cell state.
Pluripotent is a simple term for the cell that means the cell can become any other type of cell.
A recent study, which you can find on our featured studies page at longevity.pink
slash featured dash studies, investigated the effects of expressing these OSK factors in mice.
The results were nothing short of extraordinary.
The study reported that administrating these factors could significantly increase lifespan
in some cases by up to 109% in certain animal models.
This means that you take the original lifespan and add 109% of the original lifespan to it.
By introducing OSK factors using CRISPR technology instead of the traditional extremely expensive
mechanisms for gene editing, researchers were able to reset the epigenetic clock associated
with aging, leading to rejuvenated cells and improved function.
It is important to note that while the results are promising, they are based on controlled laboratory
studies. The precise administration methods, long-term effects and applicability to humans
do require further research.
David Sinclair's groundbreaking work
Harvard professor Dr. David Sinclair has been at the forefront of exploring how OSK genes
can reverse aging, but he is only rarely quoted talking about his real successes.
He is commonly quoted in the following contexts, which can be misleading and not tell the full story.
rejuvenating the eye and heart. In experiments, the expression of OSK genes restored vision in old mice
and cured glaucoma by reversing aging in retinal ganglion cells.
Skincare. He is gaining significant investment for his research from skincare companies and has set up
a skincare company called Delevy Sciences. But there are whole-body effects caused by the treatments.
In interviews, Sinclair has clearly stated that general administration of the OSK treatments
can rejuvenate whole organisms, and he has claimed publicly that he has been reversing aging through
the bodies of mice, dogs and monkeys. He goes as far as saying the students in his lab think nothing
of reversing the age of a mouse. Current regulations are clear, though. At present, CRISPR technology is
regulated. It is also new and some of the specific uses are not so well understood by safety or
legislative bodies who might need to deal with the related issues with life extension.
Still, medical professionals such as those in the micronation, Roatan, can legally access CRISPR kits.
Engaging in unauthorized DIY gene editing, especially in humans, is very dangerous and poses significant
health risks. Some of the risks to consider are tumour formation. Improper gene editing can lead
to uncontrolled cell growth or tumours. Severe tissue dysplasia, a condition where cells in tissue
undergo abnormal growth and differentiation. Genomic instability, altering DNA without precision
can result in unintended mutations. Identity and ethics. Philosophical questions arise if we alter our DNA
to what extent, to what extent do we change who we are? Unearthing ancient bacteria,
rapamycin and Easter Island. Let's quickly delve into the fascinating backstory of rapamycin.
It was discovered in the 1960s from a soil sample on Easter Island, known locally as rapanui.
This compound is produced by the bacterium Streptomyces hygroscopicus. Initially identified for its
antifungal properties, rapamycin's antifungal properties, rapamycin was later found to have
immunosuppressive effects, leading to its use in organ transplantation. More recently, in 2009,
it gained attention for its potential to extend lifespan by significant amounts.
Speculation section. Ancient legends.
The mystical aura of Easter Island and its monumental statues have long captivated imaginations.
Some speculate, purely hypothetically, that ancient peoples might have had knowledge of life-prolonging
substances like those derived from Streptomyces hygroscopicus.
Historical longevity.
Legends of individuals living extraordinary lifespans, like biblical figures, Methuselah or Noah,
reflect humanity's enduring fascination with immortality.
Myth meets science.
While there's no evidence linking ancient figures' longevity to substances like rapamycin,
it's intriguing to consider how modern science can interact with age-old myths.
Could Easter Island have been an ancient store of bacterial compounds, like the modern-day
seed vault Svalbard, but for compounds like ancient life-extending bacteria cultivations?
It's intriguing to consider whether ancient civilizations had any knowledge of natural substances that
promoted longevity, and if they may have struggled with the same fears about mass adoption as modern
scientists, like frailty and overpopulation.
Figures like Moses and Methuselah are said to have lived for several hundred years.
If they were administered these compounds, is it even possible that they didn't know about it,
and it was administered in secret in their food by one of the many people they ate with,
for example, by some secretive society.
Certainly the timekeeping of the ancients was not as good as ours,
and they could have been off by several hundred years.
While purely speculative, it's fascinating to ponder if natural compounds like those from Easter Island
could have played a role in such legends, because these characters are better documented
than many things in ancient times.
Historically, rituals involving animal sacrifices and other sacrifices were often believed to confer
blessings or longevity.
However, it might not have been as much about symbolism as people of the past believed.
It might have been because some dark members of ancient communities and societies
actually realized that consuming young blood made them live longer.
This is scientifically plausible, because young blood has many more stem cells in it.
This echoes of ancient practices are apparent in today's controversy,
like young blood transfusions, where plasma from younger individuals
is transfused into older recipients at a price of between £6,000 and £9,000 per litre,
a procedure still under scientific scrutiny.
Unlike ancient times, modern science operates under strict ethical guidelines,
emphasising the welfare of participants and the importance of informed consent.
Also, there are much more effective solutions available now,
like Everolimus or even OSK therapy.
Anyway, we've now journeyed through the exhilarating landscape of modern biotechnology,
a realm where the lines between science fiction and reality blur,
The possibility of significantly extending human life is no longer a distant dream,
but a goal within our reach.
You can help the effort to provide humanity the chance to live longer.
Engage in dialogue.
We very much hope you will discuss these topics with your friends, family and community.
Collective awareness shapes the path of scientific advancement
and helps to prevent situations where such incredibly significant discoveries are kept secret.
Stay informed.
I encourage you to explore the studies we've discussed in this podcast
by visiting longevity.pink slash featured dash studies.
Ethics first.
As we explore these frontiers, let's prioritise ethical considerations
to ensure that progress benefits humanity as a whole.
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We'd love to hear your thoughts on this.
Please follow us at longevity pink.
What excites you about these developments?
How do you feel about the ethical implications of gene editing for longevity?
In our next episodes, we'll delve deeper into the psychology and policy implications
of life extension technologies.
How should governments regulate these advancements?
What ethical framework should guide us?
We'll explore these questions and more.
Remember, the future of ageing and longevity isn't just a scientific endeavour.
It's a collective journey that involves us all.
By staying engaged, asking questions, and supporting responsible innovation,
we can help share a future where the benefits of these technologies are realised safely and ethically.
Stay curious, stay young at heart, and let's continue this exciting exploration together.