Three Paths to Longevity
Brian Rose founder of KIYA Therapeutics
I. Can fasting slow down the process of aging?
Have you ever wondered if you could pause your life in your mid-twenties? Have you ever dreamt of slowing down your body’s aging process and living for longer? Is there any real factual and scientific possibility behind these wishes? Maybe it could all be possible simply by eating a lot less…
There are several certain constants within a human’s life. We are born, we live, and we die. Part of the simple process includes the concept of aging, an intrinsic and fundamental feature of life that has fascinated humanity for hundreds of years. This topic as cropped up many a time on screen and within literature throughout history and remains a popular sci-fi tool to this day, especially within hit TV shows such as Doctor Who. However, on paper, the process of aging is a relatively simple one. As we grow older, certain stem cells within our bodies lose the ability to regenerate, thus leaving us open to attack from nasty infections, diseases, and other conditions. One example of this that we would like to focus on is the human intestinal stem cells, which, once they lose the ability to regenerate, find it far harder to recover from gastrointestinal infections and other intestinal issues.
Research from a group of MIT biologists has now revealed that you can reverse these effects of aging on the intestine with a simple 24-hour fast. By observing the effects of fasting on groups of both old and young mice, the MIT team found that stem cells have the ability to regenerate in these conditions. While in a state of fasting, the cells within the mice subjects started to break down fatty acids rather than glucose, which in turn boosted stem cell regeneration. Not only this, but the MIT team then discovered that they could achieve the same effects with the addition of a molecule that mimics the effects of Peroxisome proliferators‐activated receptors (PPARs), a breakthrough that could benefit older humans when it comes to recovering from intestinal infections or even chemotherapy.
Senior Author on the MIT paper, David Sebatini, explained: “This study provided evidence that fasting induces a metabolic switch in the intestinal stem cells, from utilizing carbohydrates to burning fat. Interestingly, switching these cells to fatty acid oxidation enhanced their function significantly. Pharmacological targeting of this pathway may provide a therapeutic opportunity to improve tissue homeostasis in age-associated pathologies.”
Further studies into the mice and the effects of fasting found that the state of fasting doubled the regenerative abilities of the intestinal stem cells, as explained by Lead Author on the paper, Maria Mihaylova.
She said: “It was obvious that fasting had this really immense effect on the ability of intestinal crypts to form more organoids, which is stem-cell-driven. This was something that we saw in both the young mice and the aged mice, and we really wanted to understand the molecular mechanisms driving this.”
The idea of fasting slowing the process of aging is not limited to this MIT study either, as research out of the Kyoto University and the Okinawa Institute of Science and Technology Graduate University has reinforced the concept.
In this study, four human subjects were asked to fast for 34 and then 58 hours to see what effect it would have on the body and the aging process. Although the results were gathered from this small pool of data, they were incredible, revealing that 44 substances increased in the human body through the process of fasting. Not only this, but many of these substances are known to decrease when a person ages, yet they increased by a factor of between 1.5 and 60 during the experiment. These metabolites, such as leucine, isoleucine, and ophthalmic acid, increasing during fasting seems to suggest that the act may indeed help people to live longer.
Technician and first author of the paper on this research, Dr. Takayuki Teruya said: “These are very important metabolites for maintenance of muscle and antioxidant activity, respectively. This result suggests the possibility of a rejuvenating effect by fasting, which was not known until now.
“Recent aging studies have shown that caloric restriction and fasting have a prolonging effect on lifespan in model animals, but the detailed mechanism has remained a mystery. It might be possible to verify the anti-aging effect from various viewpoints by developing exercise programs or drugs capable of causing the metabolic reaction similar to fasting.
“People are interested in whether human beings can enjoy the effects of prevention of metabolic diseases and prolonging life span by fasting or caloric restriction, as with model animals. Understanding the metabolic changes caused by fasting is expected to give us wisdom for maintaining health.”
While these findings are extremely interesting and are potentially ground-breaking when it comes to delaying aging effects, they do not look at data over a full life cycle. It would not be possible to conduct such an experiment using humans, but researchers from Harvard T.H Chan School of Public Health found a way around this by using C. elegans. These are nematode worms that live just a matter of two weeks, allowing the scientists to literally observe and record their entire life span.
The mitochondrial networks within cells usually switch between fused and fragmented. However, the study found that by restricting the diets of these worms or mimicking such an act through AMPK, the mitochondria remained fused into a state of youth. This also increased the lifespan of the worms in general. So, in short, you may be able to literally pause and extend your lifespan through the simple practice of fasting, or by using proteins that mimic the same results.
The lead author, Heather Weir, said: “Low-energy conditions such as dietary restriction and intermittent fasting have previously been shown to promote healthy aging. Understanding why this is the case is a crucial step toward being able to harness the benefits therapeutically. Our findings open new avenues in the search for therapeutic strategies that will reduce our likelihood of developing age-related diseases as we get older.
“Although previous work has shown how intermittent fasting can slow aging, we are only beginning to understand the underlying biology. Our work shows how crucial the plasticity of mitochondria networks is for the benefits of fasting. If we lock mitochondria in one state, we completely block the effects of fasting or dietary restriction on longevity.”
So, there we have it. Three separate studies looking at three different ways in which fasting can help to reduce the process of aging. While the research is still in its infancy, could we one day reach a stage in which this is a legitimate option in order to extend life and remain youthful?
Only time will tell.
II. Can fecal transplants from younger donors be the solution to aging?
Humanity has been searching for the secret behind the concept of aging since the dawn of time. The so-called fountain of youth has proved to be an elusive dream thus far, but could we have been throwing away the very solution for hundreds of years. Some studies have now suggested that human waste may contain the ability to increase lifespan. One person’s trash is literally another person’s treasure!
When it comes to living longer, many people would assume that a breakthrough would come via the latest technological marvel or scientific gadget, however, one very real solution may have been under our noses this whole time. In fact, humans have been actively avoiding this secret for as long as time. We are of course talking about human waste. It turns out that our toilet bowls may have been the Petri dishes for an aging breakthrough all this time and we didn’t even know it. But how could feces possibly help you to live for longer?
Perhaps the most exciting piece of research into the theory comes in the form of a study conducted by the Max Planck Institute for Biology of Ageing. As the name suggests, these researchers and scientists are at the very foreground of global aging research, and a group led by Dario Valenzano has come up with some particularly nose-flaring results!
Valenzano and his team used a batch of killifish to experiment on as part of the study as they have a lifespan of just a few months. This allowed the team to study the full life cycle of the fish to ensure that they fully captured the extent of the transplant’s effectiveness. The results gathered from these experiments go a long way to suggesting that microbiome microbes living within the body of both humans, killifish, and other animals, may have a big say in how we age through the years.
The experiment was a simple one on paper. The team took a batch of middle-aged (nine weeks) killifish and killed the microbes within their guts by using antibiotics. They then took a batch of young killifish (six weeks) and collected their feces before adding it to the tanks containing the middle-aged fish. Like humans, killifish do not actively eat feces, but by simply sharing the same tank microbes from the waste found their way into the older fishes’ sterile guts.
The corresponding results were astounding! Those killifish that ingested the fecal microbes belonging to younger fish had an increased lifespan by an impressive 37% on average. To put that into perspective, that would be like a human who normally would live until they were 80 living until nearly 110. To ensure that the results were age-dependant, the scientists also introduced the middle-aged feces into the guts of the younger fish, but there was no recorded change in lifespan. So, in short, by adding fecal matter from a young fish into the sterile gut of an older one, there was a significant increase in the latter’s life span. The power of poo!
Despite achieving such amazing results, Valenzano and his team do not yet know exactly why this happens. One possible idea is that, over time, the immune system within the middle-aged fish had allowed harmful bacteria to overpower beneficial ones. However, after the fecal transplant, the harmful bacteria build-up was removed.
Of course, there is one major flaw in the work led by Valenzano, these results have only been found within the bodies of one kind of fish, not human beings. However, a similar study in Canada looked at how mice react to a similar experiment, meaning that we could see human trials very soon. This would not be the first talk of poo power in human science either, as other studies and trials have found that fecal transplants can be used to help treat infections, malnutrition, obesity, and more.
The Canadian study dives deeper into the world of the gastrointestinal tract and the microbiome within the body. This tract and the microbiome within are said to be one of the most affected by the aging process in humans, meaning that it could also contain the secret to extended life. The gastrointestinal tract is made up of hundreds of types of bacteria, viruses, protozoa, fungi, and more, all of which contribute to a person’s health, bodily functions, brain functions, immune response, etc. As we get older, changes in the composition of gut microbes have been found to lead to illness, frailty, a loss of immunity, and more. While it is largely unknown as to why these changes occur within human guts, it is likely down to a mixture of diets, genetics, early life events, and the gut immune system. Whatever the case, the simple fact is that humans become more vulnerable to illnesses within the gut the older they are.
This new study builds on the idea raised by Valenzano and his team, supporting the simple solution of fecal transplants, however crude they may sound. In the experiment on mice, this came down to something called Peyer’s patches. These are essentially lymphatic tissue masses in the small intestine, and they play an important role in preventing harmful bacteria and maintaining a healthy immune system. Within these Peyer’s patches, we can find germinal centers, which have been found to become dysfunctional as a person ages, thus affecting their immune responses. In short, this area of the Peyer’s patch declines with age and leaves the body more open to attack from harmful bacteria. However, the Canadian study may have found a solution.
When it comes to mice, these germinal centers can be treated by fecal transplants from youngsters. They found that this defective reaction over time could be boosted by fecal matter from younger mice, thus again implying that the aging process is not as irreversible as we once thought. It will surely not be long before we see human trials in this area, as the initial animal studies are simply too promising to ignore. Scientists have already declared such fecal transplants in humans to be safe, so there are few things holding back such research from taking places, apart from relatively unknown long-term effects.
There has already been a success in using fecal transplants to treat diarrhea based infections, with the cure rate being over 90%. Some scientists are now arguing that super donors may exist, essentially hinting at certain people providing stool samples that are far more likely to have a positive influence on the gut. When you think about other illnesses associated with a change in gut bacteria, such as Alzheimer’s, some forms of cancer, asthma, allergies, heart diseases, and more, it certainly seems a worthwhile area of research.
Senior author of Frontiers in Cellular and Infection Microbiology, Dr. Justin O’Sullivan, has shed some light on the subject. He said: “The last two decades have seen a growing list of medical conditions associated with changes in the microbiome — bacteria, viruses, and fungi, especially in the gut. “In fact, we know already that changes to the gut microbiome can contribute to disease, based on studies in germ-free mice as well as clinical improvement in human patients following the restoration of the gut microbiome by transplanting stool from a healthy donor.
“The pattern of success in these trials demonstrates the existence of ‘super-donors’. We see transplants from super-donors achieve clinical remission rates of perhaps double the remaining average. Our hope is that if we can discover how this happens, then we can improve the success of fecal transplantation and even trial it for new microbiome-associated conditions like Alzheimer’s, multiple sclerosis and asthma.”
Could we soon see fecal transplants enter the mainstream for combatting aging? In short, quite possibly!
III. Can vampire-like blood transplants be a legitimate elixir of youth for humans?
We have all read about vampires in books and watched them on the big screen. In fact, vampires have been one of the staple horror figures for years now, with little kids still turning to them as go-to outfits on Halloween. One of the most chilling features of these characters is their tendency to suck blood from their victims to maintain their health, strength, and youth. This seems like a horror-devise straight from the imagination of the brilliant Bram Stoker, but could it carry scientific merit? Could blood transfers from younger humans increase a person’s life span? Was old Count Dracula right all this time?
The idea that blood infusions being able to reverse some of the negative effects of aging has been around for several years now, but three recent papers have thrown a whole lot of scientific weight behind the argument. These three published papers have shown that blood from younger donors can reverse the aging effects in areas such as memory, muscle strength, sense of smell, and endurance, as well as cognitive function declines in conditions like Alzheimer’s and heart problems.
First up, a study headed up by Saul Villeda (University of California) and Tony Wyss-Coray (Stanford), reinforces the argument that young blood can stimulate brain stem cell growth, as well as new neutrons. During the same study, the scientists also reversed the experiment by proving young mice with the blood from older creatures, recording the complete opposite effects. This is yet another indication that the secret to aging may lie in our blood.
So, how did they do it? The scientists involved connected the circulatory systems of old and young mice physically by stitching their abdominal cavities together during surgery. They also conducted the same procedure between two sets of older mice to compare the results. In this case, the elderly mice were 18 months old and the young mice were three months old. They also injected the older mice with blood plasma from young mice eight times over the course of three weeks. The teams than simply had to record the results over time to see whether the older mice attached to their younger counterparts would see any benefits, and they were not left disappointed.
Over the study period, the older mice attached to younger ones saw a greater number of new connections between brain nerve cells than those attached to other old mice. At the end of the three-week period, the mice were run through some tests to see how their memory had been affected, with the treated mice performing better in the maze experiments. These older mice that had been treated with young blood and plasma also remembered where the chamber associated with a shock was located.
Professor of Neurology at Harvard and the director of the Genetics and Aging Research Unit at Massachusetts General Hospital, Rudolph Tanzi said: “The changes are astounding in terms of rejuvenating the mice both in the periphery of the body and in the brain. I’m kind of blown away, really, by the results.
“When I first heard this story from Tony Wyss-Coray, I thought it was absolutely amazing. I thought it was too good to be true, but now you have to believe it’s real.”
The next study, conducted by a team at Harvard, found that connecting young/old mice by their circulatory systems, or injecting the old with signaling protein from the young, had a positive effect on muscles. In short, the experiment strengthened and rejuvenated the aged muscle in older mice, with stem cells being repaired, grip strength improving, and ability to run on treadmills increased. In this study, the protein used was GDF11.
Finally, the third paper, also by a team at Harvard, found that a similar experiment also had a positive effect on the older perception in aged mice. The introduction of the younger blood led to improved circulation and new nerve cells, thus improving the sense of smell that usually deteriorates through age. The improved circulation was also observed in the brain, which could explain the improved memory functions observed in the first study.
So, despite vampires being straight out of the world of fiction, it turns out that their blood-sucking hobby to stay young may be entirely scientific. While there is yet to be a widespread application for the effects found in these three studies, scientists have taken the first step in the quest to find the elixir of life. Dracula himself would be proud! Or perhaps he is…
4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4254402/ https://www.leafscience.org/transplanting-gut-microbes-from-young-to-old-mice-reverses-immune-decline/