Telomere biology and telomerase have been widely studied since the discovery of the telomere in the late 1970s. At the time of this writing, the PubMed database at the U.S. National Institutes of Health records 8,255 publications regarding telomerase.
Principle:"Telomerase can make human cells immortal."
In 1998 In 1998, a team at Geron Corporation, led by Andrea Bodnar, genetically engineered normal human cells with the gene for telomerase. These cells were able to divide almost indefinitely. In essence, the cells were made immortal - which raised the question: if the cells in our body were immortal, would we be immortal?
Extension of life-span by introduction of telomerase into normal human cells.
"Telomere loss may be responsible for aging."
One year later, a team at Maria Blasco's lab at the National Centre of Biotechnology ("CNIO") in Spain performed the first experiment demonstrating the potential for therapies based on telomere biology in a living organism. The CNIO team created a line of telomerase-deficient mice. They produced a line of mice that showed many of the classic hallmarks of human aging. This was a strong suggestion that these symptoms in humans - our "natural aging process" - are indeed a result of telomere loss.
Longevity, Stress Response, and Cancer in Aging Telomerase-Deficient Mice.
In 2000, Geron Corporation published a study that for the first time offered a strong indication that telomerase-based therapies could not only prevent, but also reverse, the aging process in humans. Human skin with telomerase added to it was grown on the backs of mice-the skin appeared younger and smoother.
Restoration of telomerase activity rescues chromosomal instability and premature aging in Terc-/- mice with short telomeres. EMBO reports, 2001.
The following year, the CNIO team performed a follow-up study to their research with telomerase-deficient mice. They bred their telomerase-deficient mice with critically short telomeres with normal mice, re-introducing the gene for telomerase. They found that this re-lengthened the telomeres in the resulting offspring. This study suggests that therapies based on telomere biology could reverse the aging process in a living mammal.
In 2003, a team led by Richard Cawthon at the University of Utah measured the telomere lengths in donated blood of individuals over 60. They found that the mortality rate of individuals with shorter telomeres was higher than those with longer telomeres, and that mortality as a result of heart disease was over three times higher in individuals with shorter telomeres. This provided solid evidence of a correllation between telomere shortening and death from old age or age-related diseases in humans.
Cawthon, et al. Association between telomere length in blood and mortality in people aged 60 years or older. The Lancet, 2003
Principle: "Aging due to wear and tear also has its root in telomere shortening."
The same year, a joint study between the University of Cape Town, South Africa, and the University of Paris, France discovered that the satellite cells responsible for muscle growth and repair in endurance athletes have telomeres that are significantly shorter than normal. Telomere-based therapies could theoretically cure even the aging we usually attribute to "wear and tear."
Collins,et al. Athletes with Exercise-Associated Fatigue Have Abnormally Short Muscle DNA Telomeres. Medicine & Science in Sports & Exercise, 2003.
Principle: "Telomerase can extend the lifespan of an organism."
In 2008, the CNIO in Spain published a study on a engineered a line of mice with cells that produced more ten times telomerase than wild mice. These mice on average lived longer. This is the first time that the lifespan of a multicellular organism has ever been extended through telomere therapy.
Tomas,et al. (Blasco) Telomerase Reverse Transcriptase Delays Aging in Cancer-Resistant Mice. Cell, 2008.
