Can we live forever?

Some scientists argue that we’re never going to achieve eternal youth and immortality, yet there’s plenty of room for longer and better life thanks to better living conditions and many miraculous strides made against disease. Over the past few decades, human longevity has significantly increased, but how close are we to immortality and eternal youth?

However, people have for centuries asked themselves if it is possible to reverse or even halt the aging process altogether. If we manage to decode this final mystery of our human biology, we might soon be able to eradicate age-related illnesses like cancer, dementia and heart problems, or at least age much healthier.

The race to invent the miracle pill is well underway. Today, international researchers are getting astonishingly close to realizing humanity’s dream of immortality.

The hunt for immortality gained traction with the discovery of Costa Rica’s so-called “Blue Zone” by Luis Rosero-Bixby. In the “Blue Zone”, on the Nicoya Peninsular, he found a remarkable number of centenarians, where arguably male life expectancy is the highest in the world. Their healthy lifestyle is one factor, but another possibility of their longevity is possibly due to the length of their telomeres - sections of DNA found at the end of chromosomes – which are longer than those of the average person.

Telomere research a field of research currently being explored by researchers around the world. But this is just one of many possible factors influencing the process of aging. For instance, senescent cells also known as “zombie cells” may also play a key role. These cells attack our body in old age and flood it with alarm signals until, at some point, the body collapses under their weight, according to some researchers.

A billion-dollar industry is already knocking eagerly at the lab doors. The first to market the miracle pill is guaranteed incredible wealth. That’s why investors are sponsoring young bio-startups around the world, and in particular in Hong Kong. At the same time, Big Tech in the USA are trying to recruit the world’s best scientists. For instance, Alex Zhavoronkov, Founder and CEO at Insilico Medicine in Hong Kong, has secured a slice of that pie, with a cash injection of more than 250 million dollars for his company’s work on aging research.

Whereas some pioneer’s visions burst like bubbles, others rush to get other, rather more dubious products onto the market. But their efficacy is now measurable. The epigenetic clock devised by Dr. Steve Horvath can measure our biological age, regardless of our actual age in years.

With his research on the thymus gland, California’s Greg Fahy has managed to not only decelerate the aging process but reverse it. His initial study on humans showed that a particular drug cocktail took an average two-and-a-half years off their age by modifying the immune system.

Young biohackers like Nina Khera from Boston wants everyone to benefit from this research. Together with friends, she’s working on the “epigenetic clock for all”.

But while we’re busy trying to counter the aging process and all the illnesses it entails, fundamental questions remain. Should we be messing with nature like this? Are we about to overwhelm the planet with more and more people? Some people think that these questions are coming far too late.

Is aging reversible? A scientific look.

According to David Sinclair a researcher from Harvard Medical School studying a field called Aging Science or Longevity Science, the first humans that will live to 150 years have already been born.

According to Sinclair, what has happened in the last 25 years is nothing short of revolutionary. And that’s not just for somebody who’s born in 2023 who will live definitely live into the 22nd century, where technologies will be far more advanced that today’s technology. But also for those of us who were born in the 1960s, 70s and 80s and even older people today.

According to Dave, at any age, we should apply the same technology and the same effort to make people live as long as possible when fighting medical conditions like cancer, heart disease, diabetes, Alzheimer’s, etc. The questions is: is aging natural and common that we should look at it differently from disease?

He recommends to not look at 99% of the information that is out there on the internet, since according t o him is all wrong! Speaking of wrong, there is a new theory of aging! We used to think antioxidants were the cure of aging, and people are taking supplement like there’s no tomorrow, and that’s all debatable.

Antioxidants have been very unsuccessful at lengthening the lifespan of anything, even a worm. They do not work well at all! The reason is that there is a lot more than free radical damage when it comes to aging.

A better approach is to tap into the body defense system against aging. We have three sets of defenses. One is call MTOR, which responds to fasting. Another called AMPK, which responds to low energy and lack of sugar. We need to keep the blood sugar levels as low as possible without fainting. And the third is a group of genes called the “sirtuins”.

The sirtuins respond to all of the things that we do: the adversity, the exercise, the fasting, etc. And this group of genes and the associated proteins that the genes make sense the environment. So that when times are thought to be tough and could threaten us, they fight harder to keep our body safe, protected and ultimately healthier to live longer, even later in life. In fact, they control the gene structure, to make us live longer controlling what is known as epigenome.

The epigenome is like the DNA with digital information and it's the structure that wraps up the DNA.. The epigenome It’s not digital, it’s mostly analog, and it’s not in a binary arrangement. Analog devices, just like the old tape recorders, or the record players, get disrupted and damaged. They get scratched. And that’s true for the epigenome as well.

The epigenome is poorly efficient at copying genetic information largely due to the three-dimensional structure of the DNA. On the other hand, the "sirtuins" that defend us are called silent information regulators. That what sirtuins stand for: SIR.

The “tu” refers to the number two for the first gene in the yeast molecule, which lifespan was extended back in the 1990s by Lenny Guarente’s lab at MIT. Therefore, the genome will be equivalent to the digital information such as a CD, and the epigenome will be the reader. The epigenome can read different songs, depending on different parts of the body, in different cell types. What David Sinclair believes is causing aging, is the skipping of those songs. And what makes the reader skips songs are the scratches, or the damage zones. So aging is essentially scratches on the CD that makes music skip. So, the epigenomic skips cells by reading the wrong genes, causing to turn them “on or off” in the wrong way; and therefore, leading to lack of ability to fight disease. We get dementia, heart disease, cancer, frailty. That’s aging!

With the new theory that he calls Information Theory of Aging, Synclair thinks we can perhaps test if epigenetic changes are causing aging. And if that’s true, is it possible to reset these structures back to the way they were, i.e. being young? Is there a backup copy of the epigenome? In other words, can we polish the CD and get rid of the scratches back to the original music?

The changes in fact are due not just to the proteins that wrap up the DNA but to the modifications that are on the DNA itself. There seem to be chemical additions called methyls, i.e. carbon atoms bonded to three hydrogen atoms. These simply structures are added to the cell when we are developing in the womb to allocate cells in different organs of the body. For instance, cells that will go in the brain, the skin, etc. These methyls will dictate the production of 26 billion cells, which have different functions in the body even though they have the same set of instructions encoded in their DNA.

What was found since 2013 by Steven Horvarth is that it is possible to read the changes of these methylation marks on the DNA that occur over time. We are all aging due to the same mechanisms and that’s a pattern that occurs very rapidly from conception until we are born and then slows down, being linear throughout our lifespan. Researchers can now measure that clock through a blood sample, a skin sample, or any part of the body.

The sample is DNA sequenced for methylation, and data are analyzed with a machine learning algorithm, that can tell the actual real age, which often differs from the chronological age. The biological age relates to changes to the epigenome and determines how old someone is.

By tweaking the epigenome we can in theory remove the scratches from the CD, and affect our chronological age.

This "Theory of Aging" has been tested in lab mice born the same day from the same mother. By manipulating the epigenome researchers have been able to accelerate aging in one mouse up to 50% in genetically identical mice ending up with a young mouse and an old mouse. They found that sirtuins genes can defend against aging, but they can also reverse other biological aspects if activated, when given them molecules synthesized from plants, since plants produce molecules that slow down the aging process.

These molecules are called xenohormetins, which are now been used in drug development. These are only one type, but there are more that have been identified. One in particular one is called NAD booster. NAD is a fuel for the sirtuins, whereas resveratrol is the accelerator pedal. So, when giving the fuel to the mice in question, in particular the sirtuins activating molecule called NMN, nicotinamide mono nucleotide, it is possible to rejuvenate the cardiovascular system of the mice and make it younger through the sirtuins. They know it woks for these sirtuins because, if they delete those genes, they don’t get the effect in the old mice. This research was published in the Journal Cell in 2018. That was only the beginning, and spring forward to 2023 and beyond the technology is and will be much more advanced, with researchers being capable to reset the age of an entire animal, leading to one day do the same for our bodies.

Researchers like Shinya Yamanaka, who won the Nobel Prize in 2016 for discovering a set of embryonic genes that could take an adult skin cell from any person and turn it into a pluripotent stem cell that could be made into any other type of tissue, can be now replicated in any lab.

Researchers have found that if they put a subset of three of those six Yamanaka embryonic genes, namely Oct4, Sox2 and Klf4, short for OSK, they can take the age of the muscle backwards, but now so far that it will become a stem cell or a tumor. This was published in December 2020 and made the cover of Nature Magazine, with the title “Turning Back Time”.

Researchers were able to repair damaged optic nerves that were crushed and dying in mice. They injected the genes in the eye and turn them on for three weeks making the neurons grow back. When the age of the neuron was measured, they found it was half its chronological age. Adult nerves do not grow back, which is an indication researchers are on the right track. They also were able to see that the CD scratches were gone.

Unfortunately, researchers don’t know yet if this applies to humans, but the procedure can be modeled in-vitro. They have conducted experiments with human pluripotent stem cells that have been engineered into little mini brains, quite similar to human brains since they show electrical activity. They actually have thoughts! These brain cells can be aged by disrupting the epigenome, and reset again, so that they get back the ability to think again, regaining electrical activity.

Does this mean one day it will be possible to reverse the age of the brain and improve the memory and other functions of the brain? It is possible, according to David Sinclair.

It could be possible to rejuvenate brains to half their age, so that they can regain their ability to learn again. But how long is this going to take? David hopes that we are at a turning point in human history.

According to Sinclair the 22nd century is going to be about biology and the ability to control age and the rate of aging, and slow down not just the aging of the body, but also the heart, and even the brain. With these tools and the age reversal tools that are just coming along we will radically change the arc of our lives in a way we can barely even imagine. We are able to reset our age by a couple of years now, which is now being published by Greg Fahy and colleagues.

Hacking your gut microbiome, a key to live to 110?

Does a Japanese 107-year-olds group of citizens hold the key to stopping aging?

Let’s face it, getting old sucks! Nobody can deny that. Yes, we do get wiser and more experienced, but at what cost?

Every other day, there’s a new diet or supplement that promises incredible benefits, including anti-aging properties and rejuvenation. The truth is that there’s no real evidence of these claims.

But, having said that, there might be a way to cure aging, as crazy as it might sound.

Traditionally, aging is viewed as a natural and inevitable process, something that happens to each and everyone of us and cannot be stopped. However, if we looked at aging from a different angle, such as a variety of symptoms caused by an underlying issue for instance, our approach to aging could be modified.

If we look at the whole package of biological changes that take place as we age and the mechanisms by which we get a whole range of different diseases, we can learn one or two things about aging.

Dr. Andrew Steele, a computation biologist, wrote a book on aging, where he explored the scientific breakthroughs that prove that aging may not be a biological inevitability after all. He suggests that aging can be modify and even cured.

If we look around the animal kingdom, we realize that aging is not a universal phenomenon. Humans have a risk of death that doubles every 8 years, but for some animals like giant tortoises, salamanders and some kinds of fish, their risk of death does not change with time. They get old, without getting elderly, fragile and sick. So, the question is: could this be applied to humans? Some people think so!

And one of the most promising areas of research on how we might be able to do it, it’s by hacking our stomachs, or the trillions of microorganisms that make up what we call the “intestinal flora” or “gut microbiome”. This is something we are born with; it’s made up of trillions of microorganisms of thousands of different species. Bacteria, fungi, parasites, and viruses. They form an ecosystem and live all over all the surfaces of our bodies.

Your microbiome is unique to everyone, kind like a fingerprint, and is formed when we are babies. However, it changes over time as we interact with the surroundings and are exposed to new environments, diets, and people. Most of these microbes live in our intestines and play a major role in our bodily functions.

Some microbes can be harmful and lead to sickness, but for the most part, we need our microbiome to function adequately. It has been called a “supporting organ” because it plays a key role in supporting human health. They stimulate our immune system, protect us from diseases, help us digest food and much more.

The gut microbiome is able to break down toxic food compounds and helping with the synthesis of vitamins and other foods. In general, the gut microbiome works with us, and works with so many different elements to support human health and keep us healthy and happy.

There has been a great amount of microbiome research and its impact on human health in recent years, and it’s changing the way we think about our bodies. For instance, disturbances of the microbiome have been associated to diseases like autism, anxiety, obesity, autoimmune conditions and even cancer. Studies shows that these disturbances can be contributing to inflammation and all kinds of diseases. It seems that the more diverse the microbiome, i.e. the larger variety of microbes, the healthier the person tends to be. And this is where the implications for aging and longevity come in: changes to our microbiome are one of the hallmarks of the aging process. Older people gut microbiome tends to be less diverse than that of younger individuals. We also know that by intervening the microbiome, we can slow the aging process when we increase its diversity, or we can accelerate it by increasing the speed of decline of the microbiome.

The above is related to the discovery of a very important connection between the microbes in our gut and the health of the body. It seems that the gut microbiome and our bodies work together in tandem and try keeping healthy as we grow older. And this means that there might be situations where the quickest treatment to a particular disease is to treat the microbiome. So, we know that different people have remarkably different gut microbiomes, so it makes sense to study the microbiome of people enjoying long, healthy and happy lives; and scientists at the Keio University of Medicine in Tokyo are doing just that.

These scientists looked at healthy centenarians, with an average age of 107 years, who have been somehow miraculously protected from diseases such as diabetes, high blood pressure, obesity and even cancer. They found that all these people had similar strains of bacteria in their guts, with one strain in particular standing out. A type of bacteria capable of synthesizing a chemical that can get rid of infections that cause things like severe diarrhea, and even death. These bacteria were like tiny bodyguards, producing bile acid, similar to that produced by the liver.

This is interesting since it seems that this type of gut microbiome could protect people from infections, pathogens, and environmental risks. And this is just one example of unique microbiomes that lead to longer lives. Then, is there a way to put these bacteria into a package and deliver them to people?

There are basically three main routes to answer this question:

Firstly, we could tweak our microbiome with specific food and supplements, like yogurt and fermented foods that are called probiotics. They work by introducing some of those good microorganisms in our gut when ingested. This treatment will be very promising in the future, once we have a better understanding of how the microbiome works.

At this moment, the effect of the probiotics found in health stores is difficult to assess because we don’t have complete information about their bacterial composition, and we don’t know exactly which bacteria are most beneficial.

Another problem is that to get these bacteria into the intestine, the supplement needs to enter the stomach, which is a nasty acidic environment, and therefore, we lack information about the type and quantity of the probiotic bacteria that will make it to the intestines in this environment.

There is also research being done on “prebiotics”, which are substances that don’t really have a nutritional value for us, but they feed the good bacteria in the gut to keep them active and alive. So, these pre- and probiotics can be combined into what’s called “synbiotics”.

Another way to intervene the microbiome is by something called “fecal transplantation”, as gross as it sounds. So, it’s basically a poo transplant, where we might swallow a capsule containing freeze-dried components of someone else’s poo –the person needs to be young since they tend to be healthier. Those poo capsules, will in theory, replenish your microbiome and make it biological younger.

However, if this option sounds disgusting and not feasible for you, there’s a middle ground option between the first two described so far, where instead of introducing actual microbes, we can figure out what specific byproduct they produce inside our intestines having a positive impact in human longevity.

So effectively, instead of promoting a more diverse microbiome, we can figure out how to give people the bacterial byproduct, which can be synthesized in a lab, and manufactured as a pill.

All these options can sound either pretty extreme or years away from being available to the public. So, the question is:

What can we do right now to keep our microbiome healthy and diverse? The answer is simple: we must eat healthy, that means a variety of fresh produce, low-carb diets, minimize sugars and processed foods, practice intermittent fasting or calorie restriction, which means just eating less and not all the time. But the truth is that it’s going to take a long time to discern the human diet and its influence on the microbiome.

It seems that longevity as a whole has seen a massive spike in interest since billionaires Jeff Bezos, Larry Page and Peter Thiel started investing in start-ups dedicated to the science of longevity. There are many factors at play, like a puzzle with thousands of pieces and the gut microbiome being only one of them.

When talking about extending life, it’s hard to see that a single pill will be able to do that, instead we have to look at the characteristics of the aging process and figure out how to mitigate their effect on human health and life expectancy.

Therefore, a combination of a healthy diet and lifestyle together with the new research in gut microbiome and genetics can give us a better insight into extending life in the years and decades to come.