The search for the fountain of youth continues because of a greater understanding of aging since Ponce De Leon’s time. We have become a society addicted to youth and restoring it with surgery, creams, teas, and even magic. Yes, some surgery looks remarkable; however, magic does not work and never did. Science and engineering is the real magic, and sometimes it even works wonders on mice. What does science say about restoring youth to humans? Well, we have come a long way, but let’s review the major step in a long journey. We started in the caves, but the bigger steps started with science in the 20th century.
Schrodinger published his famous book in 1944, What Is Life?, which describes a DNA-like molecule in every cell found within the cell nucleus. This book is a compilation of lectures he gave in Dublin, Ireland at the Institute for Advanced Studies, a famous institute at Trinity College he had founded years earlier. This work describes a complex molecule with the genetic code for life. It was the first discovery of DNA as the code for reproduction. In the scientific paper where James Watson and Francis Crick presented the structure of the DNA-helix, the molecule that carries genetic information from one generation to the other, they used the Schrodinger discovery. Watson and Crick both credited Schrodinger in their Nobel Prize acceptance speeches. It is the major step forward; in my opinion, Schrodinger should have been one of the Nobel Laureates for DNA, not just those who interpreted the x-ray work.
Schrodinger had an unconventional lifestyle. He lived together with two beautiful women, one of whom was his wife. All three lived together happily. Schrodinger was a Nobel Laureate who shared the Nobel Prize in physics with Paul Dirac. Professor Dirac was on my PhD committee and influenced me in many ways. Dirac was the most brilliant and humble man I ever met.
His wife was Eugene Wigner’s sister. Wigner is a well-known theoretical physicist. One of his daughters became a geophysicist and was at Scripps School of Oceanography. She married Robert Parker, who was also a professor at Scripps. Dirac’s other daughter was extremely talented at music; she married a physicist at Florida State. He loved to walk in the woods and eat blueberry pie with heavy cream. He loved to sail with me, and when I anchored in a cove on Key Biscayne Bay in January, he dove into the water. I asked him if it was cold; he said it was warmer than England in the summer. He was part Swiss and spoke French because his father would not speak to him in anything else; his father was born in Geneva the French speaking part of Switzerland. His mother was British, her father was a sea captain. They alawyas lived as a family in Bristol.
Dirac also told me the next century would be the biology century. He told me that in 1971, the year he signed my PhD dissertation. Years later we worked together on cosmology. Dirac was way above me in math and physics, but he sparked my interest in science fiction.
Figure 1: The double helix model of the structure of DNA, put forth by Watson and Crick based on some of the X-ray work by Rosalind Franklin and her PhD student at King’s College, Raymond Gosling. Franklin may have deserved more credit because this work was not successfully repeated by others even after the double helix was published.
Researchers used to believe science would find a longevity gene and that it could be introduced into people who do not possess the trait naturally. After searching for a single longevity gene, researchers learned that life is more complex than initially thought and there are many genes affecting lifespan. Several genes contribute to many factors that influence lifespan, and these factors are subject to myriad environmental influences, such as diet, exercise, and stress.
What do you think of when you hear Gene Therapy? If you have a defective gene, physicians can give you a healthy gene. It can be done on the cellular level to restore that gene. Harmless viruses are often used to insert the new gene directly into a cell. This gene carrier is referred to as a vector. The vector is first genetically engineered to deliver the gene. This is done by injection or IV. The new vector with gene infects the cell, which can be the tricky part to engineer. The viruses are modified so they can’t cause harm or diseases. What viruses are used? Many can be simple retroviruses, which integrate their new gene into a chromosome in the human cell. Other viruses introduce their DNA into the nucleus of the cell.
Figure 2. Gene therapy to remove or replace defective genes. The adenovirus will insert the new gene into a cell. If the treatment is successful, for example, a new gene will make a protein that improves health, longevity or treats a specific disease. Credit Wikipedia.
To date, over 2,400 trials with the objective of performing gene therapy have been completed or are still underway. The history goes back to 1980, when Martin Cline performed the first successful nuclear gene transfer in humans. In May 1989, NIH approved French Anderson to perform the first therapeutic use of gene transfer including direct insertion of human DNA into the nuclear genome.
From that humble beginning, a new form of medicine was born. Gene therapy is now defined by the precision of the procedure and the intention of direct therapeutic effects from gene transfer.
Researchers say they are now closer to a biological ‘fountain of youth.’ They have identified 30 genes out of 40,000 that are connected to biological ageing; one could be modified to extend the lifespan of humans, they suggest.
Figure 3. 16th century artist’s vision of Ponce de Leon’s imaginary fountain of youth. Today, society is even more obsessed with stopping the aging process. Scientists believe they have stumbled upon what we have been searching centuries for: but now we have a scientific fountain of youth in our sights. Image credit: Wikipedia Commons.
Search for a scientific fountain of youth hit gold at an international university ETH in Zurich, Switzerland and the Jena University Hospital in Germany. At ETH Zurich, a leading university with focus on gene therapy and engineering, Michael Ristow and his team analyzed 40,000 genes from three completely diverse creatures: the nematode, zebra fish, and mouse.
The scientists were searching for genes that regulated in an identical manner in all three organisms in each stage of young, mature, and old. Scientists took samples and measurements of the RNA molecules found in the cells of each animal, which are used, alongside DNA, to direct protein synthesis.
Using a statistical computer model, the down selected just 30 genes in common that significantly influence the ageing process of the three organisms. Ristow and colleagues were able to pinpoint the ageing process in the nematodes by selectively blocking RNA of the corresponding genes.
Figure 4. A photo of the nematode found in Wikimedia Commons.
It’s not a fountain or magic cream, it is biochemistry and epigenetics. These researchers have identified 30 genes linked to physical aging. Scientists in Switzerland and Germany searched through 40,000 genes from three different organisms: the nematode (pictured above), zebra fish, and mice.
The bcat-1 gene is particularly influential in increased lifespan. “When we blocked the effect of this gene, it significantly extended the mean lifespan of the nematode by up to 25 percent,” said Ristow. Ristow and team have taken some positive steps in finding a scientific fountain of youth, announcing in Nature Communication that they had isolated a small group of genes that modulates the aging process. Identifying the genes responsible for aging is a major first step in halting and then reversing the process. Trials in humans are needed next.
Figure 5. The cell nucleus is expanded to see the Chromosomes and DNA. Credit Wikipedia.
The researchers were also able to explain how this gene works: the bcat-1 gene carries the code for the enzyme of the same name. Natural food protein building blocks include the amino acids L-leucine, L-isoleucine, and L-valine.
When the scientists inhibited the gene activity of bcat-1, the branched-chain amino acids accumulated in the tissue, triggering a molecular signaling cascade that increased longevity in the nematodes. Moreover, the time span during which the worms remained healthy was extended.
As a measure of vitality, the researchers measured the accumulation of ageing pigments, the speed at which the creatures moved, and how often the nematodes successfully reproduced. All parameters improved when the scientists inhibited the activity of the bcat-1 gene.
Can this data be used to treat diabetes, cardiovascular disease and other diseases? Which preventative measures can improve the quality of life and lead to lower health care costs?
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Dr . Levin was born and grew up in Vermont with many winters spent in Florida as a child. As a teenager he wrote poetry, served as a lifeguard and played football. He currently enjoys sailing, exploring underwater caves, snorkeling, writing science fiction and other pursuits. After working on the Apollo and Mars projects, he returned to school to study under Nobel Laureate Paul Dirac, obtaining his PhD in 2.5 years. Dr. Levin founded two companies and served the science policy apparatus in President Ford’s administration. He has been published over 44 times in scientific literature and was awarded over 32 US patents. The science fiction writer is now emerging with his first work, a trilogy entitled 30th Century. The first award-winning book, 30th Century: Escape, is currently available on Amazon. Book two in the series, 30th Century: Revived, should be released before the end of April 2018.