Robin looks like an ordinary twelve year old girl. She is about to run a mile for gym class and expects to do well. She comes in dead last, gasping for air by the end. Fast forward one year: her hair is graying, her skin bruises easily, and she suffers from chronic fatigue. Robin, now in her thirties, is completely gray.
Robin has a rare condition that prematurely shortens telomeres. Her father had the same condition. Before passing away at forty three, both of his hips had been replaced due to bone and muscle loss. What’s happening to Robin is happening to all of us, just at a slower pace.
In 1961 Leonard Hayflick found fetal cells would divide a finite number of times. This overturned the long-held (and now ridiculous sounding) belief that all cells are immortal. The maximum number of divisions allotted to them could not be altered by his best efforts.
A 2015 study of more than 64,000 people showed that short telomeres predict earlier mortality and an increased risk of dying from cancer and cardiovascular disease. This is consistent with a large and growing literature about the relationship between telomere length and disease. However, Hayflick’s flasks overturned more than one dogma.
For most of the twentieth century it was believed that aging was the result of external factors, like exposure to cosmic rays from starlight. However, Hayflick provided compelling evidence in favor of an alternative: that aging takes place inside the cell, which means that interventions could be designed to slow, prevent, or perhaps reverse its course.
A key insight came a decade later from the laboratory of Nobel Laureate Elizabeth Blackburn. In The Telomere Effect, a book co-authored with psychology professor Elissa Epel, she describes her experiences with Tetrahymena:
“Tetrahymena is, literally, pond scum. Yet it’s almost adorable. Seen under a microscope, it boasts a plump little body and hairlike projections that make it look like a fuzzy cartoon creature…”
While studying these animals, Dr. Blackburn discovered that telomeres are just repetitive DNA sequences. However, they do not contain instructions for producing a protein. Instead, they shield your precious genetic material from the dangers of cell division. Telomeres, the protective caps at the ends of chromosomes, ensure that the information’s fidelity is maintained.
The little critters threw Dr. Blackburn another curveball in 1978. Contrary to conventional wisdom and her own expectations, their telomeres did not always shrink over time. As a matter of fact, sometimes they grew. In her own words, “this was not supposed to happen.”
Like any Nobel caliber scientist, she checked and rechecked her observations. The search for a cause led her team to an enzyme, which they dubbed telomerase. Telomerase allows cells to rebuild lost telomeres. This is not unique to slime molds. It is true for all living things.
It’s also true for every part of bodies. The most visible signs of aging are largely the result of telomere shortening and the ensuing cellular senescence (a cell that can no longer divide is called senescent). When the melanocytes that color our hair stop dividing we are left without pigmentation – white hair. When our fibroblasts reach their limit, we’re left with wrinkled skin. Senescent cells gunk things up; they secrete proinflammatory cytokines that can throw everything out of whack. Like telomere shortening itself, they are linked with a host of problems.
Researchers have investigated what affects telomere length. The results are not exactly shocking. Smoking, chronic stress (or, more precisely, maladaptive responses to stress), soft drinks, and a lack of exercise, shorten telomeres. No surprises here. While adopting healthier habits can help your telomeres and your epigenetic clock, both biomarkers of aging, this only delays the inevitable. Eppel, Blackburn’s coauthor, goes into detail about how important our responses to stress affect our telomere health.
Yet as important as healthy lifestyle choices are and as fascinating as the mind-body connection is, of more interest to those who already have good habits are experiments with telomerase induction.
De Jesus reports that telomerase induction gene therapy “had remarkable beneficial effects on health and fitness, including insulin sensitivity, osteoporosis, neuromuscular coordination and several molecular biomarkers of aging. Importantly, telomerase-treated mice did not develop more cancer than their control littermates, suggesting that the known tumorigenic activity of telomerase is severely decreased when expressed in adult or old organisms using AAV vectors.”
While De Jesus and Blasco’s work have suggested lengthening telomeres is a safe and efficacious way to address the issues associated with aging, a “Goldilocks” outlook on telomeres persisted – in other words, telomeres can be too long as well as too short. This sounds reasonable enough, as the middle ground is often the most suitable sounding place to be, but it is sometimes not the right position to take.
A paper in Nature was recently published about mice with hyper-long telomeres. The researchers found the mice had “less DNA damage with aging. Hyper-long telomere mice are lean and show low cholesterol and LDL levels, as well as improved glucose and insulin tolerance. Hyper-long telomere mice also have less incidence of cancer and an increased longevity. These findings demonstrate that longer telomeres than normal in a given species are not deleterious but instead, show beneficial effects.”
In the wake of decades of laboratory research Elizabeth Parrish, CEO of BioViva Science, took a dual therapy of follistatin and telomerase to slow down her own aging. Pre-treatment testing revealed that her telomeres were significantly shorter than other women her age. The telomerase gene therapy de-aged her telomeres by 33 years while the follistatin, a myostatin inhibiting gene therapy, had a pronounced effect on her body composition as evinced by an fMRI of her thigh – increasing muscle mass while reducing fat, with no change in overall body weight.
AAV is the same vector used by Integrated Health Systems. Beyond a potential boost in youthfulness, vigor, well-being, and protection from many age-related ailments, telomerase induction therapy also shows promise in addressing neurodegenerative disease. The promise telomerase holds is why Integrated Health Systems, in partnership with Maximum Life Foundation, is launching a study for people with moderate to mild Alzheimer’s disease.
Blackburn, Elizabeth H., and Elissa Epel. The Telomere Effect: a Revolutionary Approach to Living Younger, Healthier, Longer. Orion Spring, 2018.
Blasco, Maria A. “Telomeres and human disease: ageing, cancer and beyond.” Nature Reviews Genetics 6.8 (2005): 611.
Boukamp, Petra. “Skin aging: a role for telomerase and telomere dynamics?.” Current molecular medicine 5.2 (2005): 171-177.
Cameron, Brent, and Gary E. Landreth. “Inflammation, microglia, and Alzheimer’s disease.” Neurobiology of disease 37.3 (2010): 503-509.
Cawthon, Richard M., et al. “Association between telomere length in blood and mortality in people aged 60 years or older.” The Lancet 361.9355 (2003): 393-395.
Cawthon, Richard. “Methods of predicting mortality risk by determining telomere length.” U.S. Patent No. 9,169,516. 27 Oct. 2015.
Dubal, Dena B., et al. “Life extension factor klotho enhances cognition.” Cell reports 7.4 (2014): 1065-1076.
Flores, Ignacio, María L. Cayuela, and María A. Blasco. “Effects of telomerase and telomere length on epidermal stem cell behavior.” Science 309.5738 (2005): 1253-1256.
Hu, Ming Chang, Makoto Kuro-o, and Orson W. Moe. “Klotho and chronic kidney disease.” Phosphate and Vitamin D in Chronic Kidney Disease. Vol. 180. Karger Publishers, 2013. 47-63.
Kim, Ji-Hee, et al. “Biological role of anti-aging protein Klotho.” Journal of lifestyle medicine 5.1 (2015): 1.
Kim, Tae Nyun, et al. “Skeletal muscle mass to visceral fat area ratio is associated with metabolic syndrome and arterial stiffness: the Korean Sarcopenic Obesity Study (KSOS).” Diabetes research and clinical practice 93.2 (2011): 285-291.
Morley, John E., et al. “Sarcopenia.” Journal of Laboratory and Clinical Medicine 137.4 (2001): 231-243.
Yamamoto, Masaya, et al. “Regulation of oxidative stress by the anti-aging hormone klotho.” Journal of Biological Chemistry 280.45 (2005): 38029-38034.
