Lithium, a non-metallic element, of which Chile is the world’s largest producer, has a very important effect in reducing levels of soluble oligomers, which are the initiators of Alzheimer’s disease, by far more than 50 percent. The director of the Center for Aging and Regeneration at the Pontificia Universidad Catolica de Chile, CARE Chile UC, Nibaldo Inestrosa said during his lecture “Old age today,” presented at the Icare “Live to a hundred” Breakfast, held on Thursday, June 29th at Casa Piedra in Santiago.

“We realized that we probably had another panacea here to help the Alzheimer’s problem,” Inestrosa told the crowd, adding that “when one compares levels of amyloid peptides and structures called soluble oligomers, which are the initiators of the disease, we realize that lithium has a very important effect and lowers the levels of these proteins by an amount ​ much greater than 50 percent”.

Nibaldo Inestrosa_Icare 2017The researcher added that this shows, “that with a simple addition, in this case of a non-metallic element that is in Chilean soil, we could help the world. There is no patent here, nobody is going to make any money here, but maybe we can solve a world-wide problem. This work has been partially funded by SQM. You can understand that lithium is very important.”

AT CASA PIEDRA

During the breakfast, Icare, José Miguel Ventura a business and marketing manager at Adimark GFK presented “X-rays of the Elderly”, Consuelo Moreno, director of the Incidence Area of ​​the Senior Adult Foundation, presented “Elderly Employability,” and Iván Poduje, master architect in Urban Development, professor of the Catholic University and partner of Atisba presented “City, challenges in an aging country.”

At the start of his lecture, the 2008 National Science Prize Recipient stated that “even though, unfortunately, there is no fountain of eternal youth, you can do certain things during your life so that old age is less of an issue.” He stressed that today in Chile, 17% of the population is a senior citizen and that by 2050 this percentage will reach almost 30%.

He then referred to the centenarians (people who live to be more than 100 years old), and the so-called “blue zones” that exist in several places in the world “where these people are concentrated, who do not have the chronic diseases that we have,” he emphasized.

Inestrosa explained that, for the most part, the centenarians are women, except for the island of Sardinia in Italy, where they are mostly men for a very particular genetic reason: a group that emigrated from the Iberian Peninsula after the first glaciation, which is genetically conditioned to live longer than women.

There are also the Okinawan Islands, in Japan, where the world’s longest-living women live. Its inhabitants have very low levels of hypertension, zero colon or lung cancers, and have six times less cardiovascular disease, “which is remarkable,” he said.

Another place is Loma Linda, in California, the United States, where a group of Seventh-day Adventists settled, “who eat a lot of vegetables, have very good family relationships, and dedicate one day to rest,” Inestrosa said.

A fourth “blue zone” is in Costa Rica, in the Nicoya Peninsula, where its inhabitants eat a lot of fruit and cereals rich in antioxidants. “It is the largest of the blue zones, where more people than in all other places live to be older than 100 years old,” said the director of CARE Chile UC. “Clearly there is a situation which if we take advantage of, from the point of view of information and how we should operate, it would be different,” said the scientist.

AUTOPHAGY

Next, Nibaldo Inestrosa referred to Autophagy, which “is a phenomenon that occurs inside the cells, where there is a small stomach, called the Lysosoma, which digests all the elements that are out there. But, it has now been discovered that there is a second element that is taking material that is poorly constructed inside the cell, which joins with the Lysosoma and forms something called an Autophagosome (which includes elements of the cell). It gives way to Autophagolysosoma, which is a complex of elements that includes the mitochondria, which is what gives us the energy to function.

The researcher explained that Autophagy, “is a process by which cells eat themselves, and when this process is altered diseases occur.  Autophagy is a recent conceptual and technological acquisition, it is something that we did not know existed, and will clearly enable us to help in aging, neurodegenerative diseases, diabetes, fatty liver disease, immune problems, and cancer”.
Nibaldo Inestrosa_Icare 2017_3Inestrosa recalled that years ago, in 2006, “we found that a purified component of St. John’s Wort, which is called Hyperforin, could improve or prevent cognitive deficits in model animals of Alzheimer’s disease. And in 2011, we published our work with a synthetic derivative of Hyperforin, Tetrahydrohyperforina, which showed that when it was given to mice (which have amyloid plaques in the brain), in increasing concentrations there – were 2, 4, 6 milligrams per kilogram, there was a decrease in plaques.”

“For a long time,” added the doctor, “we think what makes the plaques, and therefore the amyloid peptide and the protein that generates them, which is the amyloid precursor protein, what causes this protein to decrease when one gives this drug. And in a paper of 2011, we say that is a possible effect on the processing of APP.”

Inestrosa argued that, indeed, “there is a small effect on APP processing, but the effect we have just found is that the precursor protein, which generates the amyloid peptide that accumulates in the senile plaques, with this drug the protein completely is removed from the cells by this system that I was talking about, autophagy. So, if one stimulates Autophagy can clearly eliminate this protein and therefore, we are not going to generate the brick that will go to form the plaques and we will not have Alzheimer’s. And this probably applies to many of the other neurodegenerative diseases such as Parkinson’s, Huntington’s, and so on. So, something that started many years ago was found today with Autophagy and we are very happy that it had to do with this phenomenon.

The researcher stated that “around 2000 we worked on a signaling pathway. When I speak of a signaling pathway I mean that inside a cell there are many elements that communicate with each other, as there are streets and roads that communicate to different cities of a country. Well, 30% of the whole human genome has to do with these communication pathways and the proteins involved in this.”

“Well, in 2000 we found that this signaling pathway controlled elements that are closely related to Alzheimer’s, such as senile plaques and tangles. And particularly when the amyloid peptide was present, degradation occurred. However, when one stimulated this pathway, which was the Wnt pathway, the cytoplasm accumulated in the beta-catenin, then it went to the nucleus and activated the transcription of genes that were survival genes, which helped a better survival of the neurons,” he said.

Nibaldo Inestrosa_Icare 2017_2Inestrosa stressed that “the interesting thing is that this requires a protein and it is quite a complicated to give a person a protein, it can, however, be reproduced exactly with Lithium. Lithium is an important element, Chile is the leading producer of Lithium worldwide, and we realized that we probably had another panacea to help the Alzheimer’s problem.”

“Indeed, when one compares levels of amyloid peptides and structures called soluble oligomers, which are the initiators of the disease, we realize that lithium has a very important effect and lowers the levels of these proteins by more than 50 percent. Showing that with a simple addition, in this case of a non-metallic element that is in the Chilean soil, we could help the world. There is no patent here, nobody is going to make any money here, but maybe we can solve a world-wide problem. This work has been partially funded by SQM. You can understand that lithium is very important.”

METABOLIC SYNDROME

Finally, the director of CARE UC referred to Metabolic Syndrome and explained that when a person has hypertension, obesity, diabetes, cardiovascular problems, he also loses his brain. “It not only affects the rest of your body, not only affects the liver, not only affects the cardiovascular system but the brain is gone…,” he said.

“There was enough evidence of this in the literature but the data had not been collected, the experiments were not targeted, so we started working directly on this and I’m finishing up now,” Inestrosa said.

He explained that “the first thing we did was to generate a Metabolic Syndrome model. This is a mouse model in which you administer fructose, the one in fruit, the one in Coca-Cola, something that we normally consume.”

“When you do this, when one has a synapse when two neurons are found and one stimulates the other, there is a communication that is one hundred percent. And when one generates what is called a tetanic stimulation, it stimulates very quickly, at a high frequency, this response that was 1, is potentiated and increases. That is the neurophysiological substrate or, if you will, electrophysiological, memory. When that increases the memory works and works well. When that cannot be generated, which is the case when one generates an animal type Metabolic Syndrome, in this case with fructose, there is simply no possibility of generating this response and there is no memory.

Inestrosa stated that “if high blood pressure is altered we change the Potassium. We have a relatively small concentration and we double the Potassium twice, that is we raise it to 2 percent and you see, this is a now transgenic animal that is going to produce Alzheimer’s disease. Transgenic animals, Alzheimer’s models, when stimulated are not able to boost their response, they are kept at very low levels. But the transgenic animals in which we increase the concentration of Potassium to double, are potentiated. This means that by modifying blood pressure, in this case by not modifying Sodium, but simply increasing Potassium, we are able to achieve this. This again suggests that Metabolic Syndrome is indeed having a very important effect on memory and learning.”

At the end of his lecture, Dr. Nibaldo Inestrosa expressed his gratitude to the National Commission for Scientific and Technological Research, Conicyt, “which has financed a large part of the project, which is a basic research project in which 80% is financed by Conicyt, ” and to SQM, which has supported the Lithium and Potassium projects.

The complete conference can be seen in this link