Blog 20 History of Research into Telomeres and Cell Aging by Mark Kingston Levin PhD award-winning author and scientist
Can we live young forever?
Figure 1. A photo of Leonard Hayflic a great biologist.
Our human cells are mortal today and thus have a limited renewal. In 1961, Leonard Hayflic discovered and described a limited lifespan due to limits in reproduction cycles of each cell, which is called the “Hayflick limit” of cellular reproductive cycles. Hayflic related these cycles to the number of unique DNA repeats located on the endcaps of the chromosomes. These DNA repeats, known as telomeres, protect the chromosomes for a limited time and then shorten over time, causing aging. Before this work by Hayflick, the dominant view in biology was set by Nobel laureate Alexis Carrel who hypothesized that normal cells are immortal.
Figure 2. Professor Julian Chen, in the School of Molecular Sciences at Arizona State University, recently published a paper that uncorks the tube of truth and the biochemistry of this critical step in the telomerase catalytic cycle. (Image Credit Wikipedia)
Please see Y. Chen, J.D. Podlevsky, D. Logeswaran and J.J.-L. Chen (Feb. 2018). A single nucleotide incorporation step limits human telomerase repeats addition activity. EMBO. J. 37: e97953, DOI 10.15252/emboj.20179795
This catalytic cycle determines the ability of the human telomerase enzyme to synthesize DNA “repeats” (specific DNA segments of six nucleotides) onto chromosome ends, and so affords immortality in cells. Uncovering the entire cell biochemistry may someday lead to telomerase engineering toward effective anti-aging therapeutics, according to Chen.
Figure 3. This artist drawing depicts the telomerase enzyme as well as telomeres relative to a chromosome that looks like an X in the upper portion of the illustration.
The telomeres get smaller with time, and the telomerase possibly can be engineered to reverse the aging process without causing cancer. It is a tricky maneuver; however, as we understand more about the biology and chemistry, maybe we can make progress in extending lifespan and health span. Chen and his team identified the braking mechanism used by the telomerase enzyme to slow down. The key step synthesizes six nucleotides, GGTTAG, and then repeats the cycle.
In 2015, Helen Blau, PhD, professor of microbiology and immunology at Stanford and director of the university’s Baxter Laboratory for Stem Cell Biology, developed an important patent on how to lengthen telomeres about forty times that of the untreated cells. The novel process efficiently increases the length of human telomeres located on the endcaps of the chromosomes as shown below:
Figure 4. The Chromosome with telomeres is expanded to show it is made of DNA. Credit Wikipedia
Dr. Blau writes that “treated cells behave as if they are much younger than untreated cells, multiplying with abandon in the laboratory dish rather than stagnating or dying.” Dr. Blau used a modified RNA to improve these results. She goes on to explain that “telomeres are about 8,000-10,000 nucleotides long. They shorten with each cell division, however, and when they reach a critical length the cell stops dividing or dies.” Thus, the process acts like a battery starting off with full power but then drops and dies.
Figure 5. Professor Helen Blau was born in the UK and now is at Stanford University. Dr. Blau makes a major step in lengthening telomeres. Dr. Blau’s discoveries gave scientists a new process for cellular reprogramming and its application to stem cell biology.
“Now we have found a way to lengthen human telomeres by as much as 1,000 nucleotides, turning back the internal clock in these cells by the equivalent of many years of human life,” said Dr. Blau. “This greatly increases the number of cells available for studies such as drug testing or disease modeling.” Her discoveries led to the development of the field of stem cell biology and regenerative medicine. Dr Blau has developed methods to identify molecules that rejuvenate the function of the aged stem cell population and enhance muscle regeneration, which is reverse aging in many ways.
Blau published many famous papers; one paper describing exciting research was published recently in the FASEB Journal. Blau, who also holds the Donald E. and Delia B. Baxter Professorship, is the senior author. Others included John Ramunas, PhD, of Stanford and Eduard Yakubov, of the Houston Methodist Research Institute. This new approach is mostly used in cultured cells in lab vessels, not yet in humans. Ramunas, Yakubov, Cooke and Blau are inventors on the patent for the use of modified RNA for telomere extension.
Figure 6. Professor Elizabeth H. Blackburn was born near Hobart Tasmania Australia. She was award a Nobel Prize in 2009 and is now the Morris Herzstein Professor of Biology and Physiology in the Department of Biochemistry and Biophysics at the University of California San Francisco (UCSF).
Coauthor Elizabeth Blackburn, PhD, tells us about her new book The Telomere Effect. She explains the science behind ways to stay young longer with diet and exercise. The book covers what we each can do now and much more. It is written in down-to-earth American English and is easy to understand. It may be easier for non-science educated people to read her work than my blogs. If you want more layman’s terms, I am willing to try; please just give me feedback at my email: firstname.lastname@example.org.
Figure 7. A common diagram of a chromosome, with telomeres on the ends shown in gold and green. Credit Wikipedia
Mark Kingston Levin PhD award-winning author and scientist
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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, was released April 29, 2018. It is now available on Amazon, Barnes & Noble, and other retailers.