- ▷ Telomere length and aging: 5 ways to maintain healthy telomeres
- Get info on the Telomere Theory of Aging: What It Is and How It Works
- Telomere extension turns back aging clock in cultured human cells, study finds
- Transient effect an advantage
- Potential uses for therapy
- Telomeres, lifestyle, cancer, and aging
- Hidden secret of immortality enzyme telomerase: Can we stay young forever, or even recapture lost youth?
- You may have more control over aging than you think, new book says
▷ Telomere length and aging: 5 ways to maintain healthy telomeres
26 November 2018
The key point in this equation is that telomeres shortening rate can be positively impacted by our daily choices and habits. In the following lines you will discover some of the most important elements to have into account to set yourself on the right path towards your best self.
Aging is the accumulation of damage. Biological death takes place because a worn-out tissue cannot forever renew itself, a consequence of the fact that the capacity of cell division is not everlasting but finite. The main idea here is that there is a specific limitation on the number of divisions that somatic cells undergo in the course of an individual life.
Telomeres are known to be one of the major determinants of aging. They are the protective cap that prevents the ends of chromosomes from fusing to each other and allow chromosome ends to attach to the nuclear envelope.
Long telomere lengths are related to greater longevity, while shorter lengths are related to aging diseases such as cancer, arthritis and heart disease. Telomerase enzyme can repair telomere attrition. The enzyme has protein subunit (hTERT) and an RNA subunit.
It helps to maintain telomere length by adding telomeric repeats “TTAGGG” to ends of the chromosome during DNA replication.
Lifestyle plays an important factor in determining telomere length and telomerase activity. Factors such as obesity, stress, alcohol consumption, smoking, air pollution and low physical activity can significantly increase the rate of telomere shortening, cancer risk and affect longevity.
Here are 5 ways to maintain healthy telomere length which could significantly influence longevity:
According to a study conducted by NHANES, people who have high levels of physical activity showed a significantly longer telomere length compared to people who are sedentary or moderately active. Adults involved in high physical activity were determined to have a benefit of 9 years less of biological aging than their sedentary counterparts.
Obesity is related to high levels of oxidative stress. This condition causes DNA damage and increases the rate of telomere shortening.
High percentages of body fat could activate adipocytokines that create oxidative stress on cells, damaging their chromosomes’ telomeres placed inside the cell’s nucleus.
Hence maintaining a healthy weight and eating well is essential to foster and keep a healthy immune system, protecting telomere length. Food rich in antioxidants has a positive effect promoting antioxidants balance in your body, which protects DNA from oxidative stress.
Low telomerase activity and short telomere length have been associated with psychological, chronic and life stress in a number of studies. These factors were reported to significantly affect the length of telomeres, as well as telomerase activity, raising levels of oxidative stress in immune system cells.
Stress affects catecholamine production which has a significant influence on the immune role that involves the NK cell activity and lymphocyte proliferation. Hence, when inflammation occurs and repair process is not effective, it could lead to disease pathogenesis.
Once again, minimizing oxidative stress in the body becomes essential to maintain healthy telomeres.
There are some supplements that have been shown to decrease the effect of aging in our system. For example, N-acetyl-cysteine (NAC) as very powerful antioxidant properties.
Vitamins C & E may limit oxidative damage to telomeric DNA that would otherwise cause shortening of telomere length.
Magnesium deficiency is also accompanied by an increase in oxidative stress, as this element is required in the catalytic activity of a wide array of enzymes, including those involved in DNA replication, DNA repair and RNA synthesis.
Similarly, dietary zinc deficiency is also associated with oxidative damage. Zinc supplementation reduces the incidence of infection, being this another factor that leads to telomere attrition by inducing higher cell turnover. Nevertheless, choosing the right supplements should be always done with the guidance of an expert.
Smoking contributes to increased oxidative damage and inflammation. This causes leukocyte telomere shortening by promoting excessive cell turnover and replicative senescence. People who smoke have been reported in studies to have a shorter telomere length than those who did not smoke.
Additionally, different studies have linked excessive alcohol consumption with faster biological aging at a cellular level. Heavy use of alcohol is also associated with thiamine deficiency, more generally known as vitamin B1, an important nutrient for taking energy from food and turning it into energy for the brain, nerves and heart.
Long term B1 deficiency leads to higher oxidative stress levels, with the associated effects on telomere length that have been already exposed.
To conclude, it is essential to remember that genetics factors accounts for just around 30% of an individual’s telomere length. Environmental factors, including lifestyle choices, play a much greater role on a person’s cellular health and aging process. Hence, we do certainly have a lot to do in order to maximize our health span and take our life potential to the point where it must be.
If you want to know how your diet and lifestyle components are impacting your cellular health and aging process, consider testing your telomeres with Life Length´s TAT® technology to set and keep yourself on the right path towards your best future.
Get info on the Telomere Theory of Aging: What It Is and How It Works
Alessia Pederzoli/Taxi/Getty Images
The discovery of telomeres completely changed the way researchers study longevity and the process of aging. In fact, the researchers who discovered telomeres won the Nobel Prize in Physiology or Medicine in 2009. Telomeres are bits of “junk DNA” that are located at the ends of chromosomes. They protect your real DNA every time a cell divides.
Each time a cell divides, the DNA unwraps, and the information within is copied. Because of how cells divide, that very last bit of a chromosome, the telomere, cannot be completely copied. A little bit has to be cut off.
It is thought that, as a cell divides, the telomeres become shorter and shorter each time until they are gone.
At this point, the so-called “real” DNA cannot be copied anymore, and the cell simply ages and is no longer able to replicate.
In population-level studies, researchers have found that older people have shorter telomeres. Eventually, the cells with shorter telomeres can no longer replicate. This affects more and more cells over time, leading to tissue damage and the dreaded signs of again.
Most cells can replicate approximately 50 times before the telomeres become too short.
Some researchers believe that telomeres are the supposed “secret to longevity” and that there are circumstances in which telomeres will not shorten.
For example, cancer cells don't die (which is the main problem) because they activate an enzyme called telomerase that adds on to the telomeres when cells divide.
All cells in the body have the capacity to produce telomerase, but only certain cells – including stem cells, sperm cells, and white blood cells – need to produce the enzyme. These cells need to replicate more than 50 times within a lifetime, so by producing telomerase they aren't affected by telomere shortening.
Shorter telomeres are not only associated with age but with disease too. In fact, shorter telomere length and low telomerase activity are associated with several chronic preventable diseases. These include hypertension, cardiovascular disease, insulin resistance, type 2 diabetes, depression, osteoporosis, and obesity.
No. And that’s a big surprise. Researchers in Sweden discovered that some people’s telomeres do not necessarily get shorter over time. In fact, they found that some people’s telomeres can even get longer. This variation at the individual level was undetectable by prior studies that averaged results over a large population.
In the study, 959 individuals donated blood twice, 9 to 11 years apart. On average, the second samples had shorter telomeres than the first. However, approximately 33 percent of those studied had either a stable or increasing telomere length over a period of about 10 years.
What does this mean? It's unclear. It could be that those people have an amazing cellular anti-aging mechanism; it could be that they have an early sign of cancer (researchers tried to rule this out), or it could be fairly meaningless. What we do know for sure is that aging is a lot more complicated than simply looking at the shortening of telomeres.
The telomere theory is one of the theories of aging. This is a developing field, and new discoveries may disprove it or they may lead to using the theory to develop treatments for diseases and conditions.
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- Nordfjäll K, Svenson U, Norrback K-F, Adolfsson R, Lenner P, Roos G. The individual blood cell telomere attrition rate is telomere length dependent. PLoS Genetics, February 13, 2009 DOI: 10.1371/journal.pgen.1000375
Telomere extension turns back aging clock in cultured human cells, study finds
A paper describing the research was published today in the FASEB Journal. Blau, who also holds the Donald E. and Delia B. Baxter Professorship, is the senior author. Postdoctoral scholar John Ramunas, PhD, of Stanford shares lead authorship with Eduard Yakubov, PhD, of the Houston Methodist Research Institute.
The researchers used modified messenger RNA to extend the telomeres. RNA carries instructions from genes in the DNA to the cell’s protein-making factories.
The RNA used in this experiment contained the coding sequence for TERT, the active component of a naturally occurring enzyme called telomerase.
Telomerase is expressed by stem cells, including those that give rise to sperm and egg cells, to ensure that the telomeres of these cells stay in tip-top shape for the next generation. Most other types of cells, however, express very low levels of telomerase.
Transient effect an advantage
The newly developed technique has an important advantage over other potential methods: It’s temporary.
The modified RNA is designed to reduce the cell's immune response to the treatment and allow the TERT-encoding message to stick around a bit longer than an unmodified message would.
But it dissipates and is gone within about 48 hours. After that time, the newly lengthened telomeres begin to progressively shorten again with each cell division.
The transient effect is somewhat tapping the gas pedal in one of a fleet of cars coasting slowly to a stop.
The car with the extra surge of energy will go farther than its peers, but it will still come to an eventual halt when its forward momentum is spent.
On a biological level, this means the treated cells don’t go on to divide indefinitely, which would make them too dangerous to use as a potential therapy in humans because of the risk of cancer.
This new approach paves the way toward preventing or treating diseases of aging.
The researchers found that as few as three applications of the modified RNA over a period of a few days could significantly increase the length of the telomeres in cultured human muscle and skin cells.
A 1,000-nucleotide addition represents a more than 10 percent increase in the length of the telomeres.
These cells divided many more times in the culture dish than did untreated cells: about 28 more times for the skin cells, and about three more times for the muscle cells.
“We were surprised and pleased that modified TERT mRNA worked, because TERT is highly regulated and must bind to another component of telomerase,” said Ramunas. “Previous attempts to deliver mRNA-encoding TERT caused an immune response against telomerase, which could be deleterious.
In contrast, our technique is nonimmunogenic. Existing transient methods of extending telomeres act slowly, whereas our method acts over just a few days to reverse telomere shortening that occurs over more than a decade of normal aging.
This suggests that a treatment using our method could be brief and infrequent.”
Potential uses for therapy
“This new approach paves the way toward preventing or treating diseases of aging,” said Blau. “There are also highly debilitating genetic diseases associated with telomere shortening that could benefit from such a potential treatment.”
Blau and her colleagues became interested in telomeres when previous work in her lab showed that the muscle stem cells of boys with Duchenne muscular dystrophy had telomeres that were much shorter than those of boys without the disease. This finding not only has implications for understanding how the cells function — or don’t function — in making new muscle, but it also helps explain the limited ability to grow affected cells in the laboratory for study.
The researchers are now testing their new technique in other types of cells.
“This study is a first step toward the development of telomere extension to improve cell therapies and to possibly treat disorders of accelerated aging in humans,” said John Cooke, MD, PhD. Cooke, a co-author of the study, formerly was a professor of cardiovascular medicine at Stanford. He is now chair of cardiovascular sciences at the Houston Methodist Research Institute.
“We’re working to understand more about the differences among cell types, and how we can overcome those differences to allow this approach to be more universally useful,” said Blau, who also is a member of the Stanford Institute for Stem Cell Biology and Regenerative Medicine.
“One day it may be possible to target muscle stem cells in a patient with Duchenne muscular dystrophy, for example, to extend their telomeres. There are also implications for treating conditions of aging, such as diabetes and heart disease. This has really opened the doors to consider all types of potential uses of this therapy.”
Other Stanford co-authors of the paper are postdoctoral scholars Jennifer Brady, PhD, and Moritz Brandt, MD; senior research scientist Stéphane Corbel, PhD; research associate Colin Holbrook; and Juan Santiago, PhD, professor of mechanical engineering.
The work was supported by the National Institutes of Health (grants R01AR063963, U01HL100397 U01HL099997 and AG044815), Germany’s Federal Ministry of Education and Research, Stanford Bio-X and the Baxter Foundation.
Ramunas, Yakubov, Cooke and Blau are inventors on patents for the use of modified RNA for telomere extension.
Information about Stanford’s Department of Microbiology and Immunology, which also supported the work, is available at http://microimmuno.stanford.edu.
Telomeres, lifestyle, cancer, and aging
Papers of particular interest, published within the annual period of review, have been highlighted as:
• of special interest
•• of outstanding interest
Additional references related to this topic can also be found in the Current World Literature section in this issue (pp. 101–102).
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Hidden secret of immortality enzyme telomerase: Can we stay young forever, or even recapture lost youth?
Can we stay young forever, or even recapture lost youth?
Research from the laboratory of Professor Julian Chen in the School of Molecular Sciences at Arizona State University recently uncovered a crucial step in the telomerase enzyme catalytic cycle.
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 afford immortality in cells. Understanding the underlying mechanism of telomerase action offers new avenues toward effective anti-aging therapeutics.
illustration depicting the enzyme telomerase This figure depicts the enzyme telomerase as well as telomeres relative to a chromosome.
Typical human cells are mortal and cannot forever renew themselves. As demonstrated by Leonard Hayflick a half-century ago, human cells have a limited replicative lifespan, with older cells reaching this limit sooner than younger cells.
This “Hayflick limit” of cellular lifespan is directly related to the number of unique DNA repeats found at the ends of the genetic material-bearing chromosomes.
These DNA repeats are part of the protective capping structures, termed “telomeres,” which safeguard the ends of chromosomes from unwanted and unwarranted DNA rearrangements that destabilize the genome.
Each time the cell divides, the telomeric DNA shrinks and will eventually fail to secure the chromosome ends.
This continuous reduction of telomere length functions as a “molecular clock” that counts down to the end of cell growth.
The diminished ability for cells to grow is strongly associated with the aging process, with the reduced cell population directly contributing to weakness, illness, and organ failure.
The fountain of youth at molecular level
Counteracting the telomere shrinking process is the enzyme, telomerase, that uniquely holds the key to delaying or even reversing the cellular aging process. Telomerase offsets cellular aging by lengthening the telomeres, adding back lost DNA repeats to add time onto the molecular clock countdown, effectively extending the lifespan of the cell.
Telomerase lengthens telomeres by repeatedly synthesizing very short DNA repeats of six nucleotides — the building blocks of DNA — with the sequence “GGTTAG” onto the chromosome ends from an RNA template located within the enzyme itself.
However, the activity of the telomerase enzyme is insufficient to completely restore the lost telomeric DNA repeats, nor to stop cellular aging.
The gradual shrinking of telomeres negatively affects the replicative capacity of human adult stem cells, the cells that restore damaged tissues and/or replenish aging organs in our bodies.
The activity of telomerase in adult stem cells merely slows down the countdown of the molecular clock and does not completely immortalize these cells.
Therefore, adult stem cells become exhausted in aged individuals due to telomere length shortening that results in increased healing times and organ tissue degradation from inadequate cell populations.
Tapping the full potential of telomerase
Understanding the regulation and limitation of the telomerase enzyme holds the promise of reversing telomere shortening and cellular aging with the potential to extend human lifespan and improve the health and wellness of elderly individuals.
Research from the laboratory of Chen and his colleagues, Yinnan Chen, Joshua Podlevsky and Dhenugen Logeswaran, recently uncovered a crucial step in the telomerase catalytic cycle that limits the ability of telomerase to synthesize telomeric DNA repeats onto chromosome ends.
“Telomerase has a built-in braking system to ensure precise synthesis of correct telomeric DNA repeats.
This safe-guarding brake, however, also limits the overall activity of the telomerase enzyme,” said Professor Chen.
“Finding a way to properly release the brakes on the telomerase enzyme has the potential to restore the lost telomere length of adult stem cells and to even reverse cellular aging itself.”
This intrinsic brake of telomerase refers to a pause signal, encoded within the RNA template of telomerase itself, for the enzyme to stop DNA synthesis at the end of the sequence 'GGTTAG'. When telomerase restarts DNA synthesis for the next DNA repeat, this pause signal is still active and limits DNA synthesis.
Moreover, the revelation of the braking system finally solves the decades-old mystery of why a single, specific nucleotide stimulates telomerase activity.
By specifically targeting the pause signal that prevents restarting DNA repeat synthesis, telomerase enzymatic function can be supercharged to better stave off telomere length reduction, with the potential to rejuvenate aging human adult stem cells.
Human diseases that include dyskeratosis congenita, aplastic anemia, and idiopathic pulmonary fibrosis have been genetically linked to mutations that negatively affect telomerase activity and/or accelerate the loss of telomere length.
This accelerated telomere shortening closely resembles premature aging with increased organ deterioration and a shortened patient lifespan from critically insufficient cell populations.
Increasing telomerase activity is the seemingly most promising means of treating these diseases.
While increased telomerase activity could bring youth to aging cells and cure premature aging- diseases, too much of a good thing can be damaging for the individual.
Just as youthful stem cells use telomerase to offset telomere length loss, cancer cells employ telomerase to maintain their aberrant and destructive growth.
Augmenting and regulating telomerase function will have to be performed with precision, walking a narrow line between cell rejuvenation and a heightened risk for cancer development.
Distinct from human stem cells, somatic cells constitute the vast majority of the cells in the human body and lack telomerase activity. The telomerase deficiency of human somatic cells reduces the risk of cancer development, as telomerase fuels uncontrolled cancer cell growth. Therefore, drugs that increase telomerase activity indiscriminately in all cell types are not desired.
Toward the goal of precisely augmenting telomerase activity selectively within adult stem cells, this discovery reveals the crucial step in telomerase catalytic cycle as an important new drug target.
Small molecule drugs can be screened or designed to increase telomerase activity exclusively within stem cells for disease treatment as well as anti-aging therapies without increasing the risk of cancer.
Materials provided by Arizona State University. Note: Content may be edited for style and length.
You may have more control over aging than you think, new book says
Molecular biologist Elizabeth Blackburn shared a Nobel Prize for her research on telomeres — structures at the tips of chromosomes that play a key role in cellular aging. But she was frustrated that important health implications of her work weren’t reaching beyond academia.
So along with psychologist Elissa Epel, she has published her findings in a new book aimed at a general audience — laying out a scientific case that may give readers motivation to keep their new year’s resolutions to not smoke, eat well, sleep enough, exercise regularly, and cut down on stress.
The main message of “The Telomere Effect,” being published Tuesday, is that you have more control over your own aging than you may imagine. You can actually lengthen your telomeres — and perhaps your life — by following sound health advice, the authors argue, a review of thousands of studies.
“Telomeres listen to you, they listen to your behaviors, they listen to your state of mind,” said Blackburn, president of the Salk Institute for Biological Studies in La Jolla, Calif.
Telomeres sit at the end of strands of DNA, the protective caps on shoelaces. Stress from a rough lifestyle will shorten those caps, making it more ly that cells will stop dividing and essentially die.
Too many of these senescent cells accelerates human aging, the pair say.
This doesn’t cause any particular disease, but research suggests that it hastens the time when whatever your genes have in store will occur — so if you’re vulnerable to heart disease, you’re more ly to get it younger if your telomeres are shorter, said Epel, director of the University of California, San Francisco’s Aging, Metabolism and Emotions Center.
“We can provide a new level of specificity and tell people more precisely with clues emerging from telomere science, what exactly about exercise is related to long telomeres, what exact foods are related to long telomeres, what aspects of sleep are more related to long telomeres,” Epel added.
Other researchers in the field praised Blackburn and Epel’s efforts to make telomere research relevant to the general public, though several warned that it risked oversimplifying the science.
“I think it’s a very difficult thing to prove conclusively” that lifestyle can affect telomere length and therefore lifespan, said Harvard geneticist and anti-aging researcher David Sinclair. “To get cause-effect in humans is impossible, so it’s associations.”
Judith Campisi, an expert on cellular aging at the Buck Institute for Research on Aging in Novato, Calif., said the underlying research is solid. “If you have a terrible diet and you smoke, you’re definitely shortening your life, and shortening your telomeres,” she said.
Short telomeres increase the lihood of cells becoming senescent and producing molecules that lead to inflammation, which she said is a huge risk factor for every age-related disease. “So there is a link there,” Campisi said, “it’s just not this exclusive magic bullet, that’s all.”
Cells can age in different ways, so someone could have lots of aging cells but normal-looking telomeres. “If all aging was due to telomeres, we would have solved the aging problem a long time ago,” she said.
Elizabeth Blackburn (left) and Elissa Epel, authors of “The Telomere Effect.” Digital Natives
In a telephone interview from her publisher’s office in New York, Blackburn said the best part of the telomere research is that it’s quantifiable, giving people more specific direction than the advice your mother may have given you to get off the couch and exercise.
“Your mother didn’t tell you if you had to run marathons every week, or if three to four times a week is enough,” she said. Telomere research suggests that extreme exercise isn’t necessary to live healthier longer.
Also, Blackburn said, her research suggests that lengthening telomeres with medications could be dangerous — that lifestyle changes are far safer than a pill.
One surprise from the research: You don’t actually need a full eight hours of sleep to benefit your telomeres. Seven is enough, as long as you feel well-rested. “That’s something quite useful, so people won’t lie awake fretting that they’re not getting eight hours,” Blackburn said.
One of the challenges with telomere research is that most studies measure the length of telomeres in blood cells. But it may be that the liver is aging faster or slower than the blood — we’re not all one age throughout, Campisi said.
By measuring telomere length in the blood, “what you’re really reporting on is the capacity of immune stem cells to function well,” said Matt Kaeberlein, who studies the molecular basis of aging at the University of Washington. “What this may be really telling us is the immune system may be particularly sensitive to lifestyle and environmental factors.”
Kaeberlein said he’s only at the periphery of telomere research, but is skeptical about the predictive value of shorter versus longer telomeres.
“It’s not at all clear whether the methods are quantitative enough or of high enough resolution to really make those kinds of arguments,” Kaeberlein said. “I think it has the potential to be a biomarker predicting health outcomes, but I don’t know that I would feel comfortable saying people should make lifestyle changes a measure of their telomere length,” he said.
Sara Gottfried did. A Harvard-trained gynecologist in Berkeley, Calif., she said a test of her telomere length put her 20 years beyond her biological age, and shocked her into action.
“It was an interesting anecdotal experiment,” said Gottfried, whose examination led to a book, due out in March, called “Younger: A Breakthrough Program to Reset Your Genes, Reverse Aging, and Turn Back the Clock 10 Years.” “It organized my thinking around the levers of health span — food, sleep, exercise, lean body mass, stress — how so many of us are in a failure state, which I think accelerates aging.”