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Hormone Replacement Therapy, Physical Medicine & Rehabilitation, Anti-Aging
Dr. Edmund Chein | edmundchein

The History of Telomere and Telomerase

Dec 9th 2014 at 2:40 AM

Telomeres are cap-like structures at the end of our chromosomes that shorten every time a human cell divides. The length of every individual’s telomeres is closely associated with his or her biological age. Research has suggested that controlling telomere length has the potential to treat many diseases associated with aging, thereby allowing humans to live physiologically and biologically "younger"—that is, with increased vitality and vibrancy, and in better health—and to attain a chronological age that is beyond the observed maximum human life span of 122 years.

The initial discovery of the telomere occurred in 1938. Almost 60 years later (in 1997), scientists first cloned telomerase, the enzyme responsible for telomere maintenance and repair. Let’s further examine the research completed between the discovery of telomeres and the first cloning of telomerase, as well as the vast amount of research completed since 1997—including the 2009 Nobel Prize in Medicine, which was awarded for telomere and telomerase research.

Timeline of Telomere and Telomerase Breakthroughs

In 1938, geneticist Herman Muller1 first discovered and named telomeres in the fruit fly when observing structures that served as protective caps on the chromosomes’ ends, preventing DNA damage. Two years later, geneticist Barbara McClintock2 discovered that without telomeres, chromosomes would fuse to each other, causing cell death. However, neither Muller nor McClintock realized that telomere shortening was associated with human aging.

telomereThe nature of telomere shortening was first proposed by Soviet scientist Alexei Olovnikov and American scientist James Watson, in 1971 and 1972, respectively.3 Both scientists realized that every cell replication must result in a loss of some DNA. Olovnikov was the first to posit that telomere shortening was the mechanism that limited the number of times a cell could divide.

In 1975, Elizabeth Blackburn (Yale University) and Jack Szostak (Harvard Medical School) discovered that yeast cells were able to re-elongate their telomeres.4 They theorized that the yeast’s telomeres were lengthened by an enzyme that would later be named telomerase. In 1984, Blackburn and one of her students, Carol Greider, isolated telomerase.5 (As previously mentioned, in 2009, Blackburn, Greider, and Szostak were awarded the Nobel Prize in Medicine for their work in discovering the structure and mechanism of telomeres and telomerase.6)

In 1998, a team at Texas University Southwest Medical School added the gene for telomerase to normal human cells by means of a plasmid, creating a line of cells that were able to divide indefinitely.7 (A plasmid is an extrachrosomal ring of DNA; plasmids replicate autonomously and are most typically found in bacteria.) This first-time cloning of telomerase demonstrated that normal human cells can be made immortal.

In 2003, a team led by Richard Cawthorn at the Utah State University studied 143 individuals over the age of 60 who had donated their blood between 1982 and 1986 (20 years prior), measuring the telomere length in their blood cells. They found that the mortality rate of those individuals with shorter telomeres was nearly twice as high as that of individuals with longer telomeres.8 This provided solid evidence of correlation between telomere shortening and death from old age or age-related diseases in humans.

In 2008, scientists led by Dr. Maria Blasco at the National Center for Biotechnology in Spain created a line of mice whose cells had been engineered to produce more telomerase than normal mice. This allowed these genetically engineered mice to live an average of 138 percent longer than normal mice.9 Furthermore, these mice stayed healthier and more athletic for a longer time. Dr. Chein's represented the first time that the life span of a multicellular mammal had ever been extended, and the quality of life improved, through telomere lengthening therapy.



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