Mar
14
2020

Telomeres are Important

In the first place, Dr. Joseph Raphaele reviewed why telomeres are important at a Conference in Las Vegas in December 2019. This was at the 27th Annual World Congress on Anti-Aging Medicine in Las Vegas from Dec. 13 to 15, 2019. The actual title of his lecture was: “Telomeres in 2019; clinical developments and cutting-edge applications”.

Notably, Dr. Raphaele reviewed how various animals have quite different life expectancies. First, the Aldabra giant tortoises, for instance can live up to 152 years. Second, the house mouse can at the most live up to 6 years, but its predator, the cat lives up to 38 years. Finally, humans can live up to 122.5 years.That is to say, the average mortality rate doubling curve of man is 8 years. Dr. Raphaele introduced the terms “lifespan” and “health-span”.

Lifespan versus health-span

The first thing to remember is that our lifespan is defined by the number of years we live. On the contrary, the health-span is defined by the number of years you do not have any disease and your physical and mental health are good. Dr. Raphaele explained that for the most part the body’s organs have a limit of functioning after 80. For this reason the kidneys, the maximum heart rate, the maximum breathing capacity and the maximum work rate (oxygen uptake) all decline after the age of 80. It is important to realize that in 1961 Dr. Leonard Hayflick showed that there is a limit of how often cells can divide. After 60 doublings cells in tissue culture either die or just stop dividing. The built-in molecular clock resides in the telomeres. The telomeres are the caps at the end of the chromosomes in the cell’s nucleus.

Telomeres and their function in aging

In a word, what is the function of telomeres? In essence, the telomeres protect the integrity of our genes. For the most part, they protect the chromosomes from deteriorating, prevent DNA fusion and massive instability of the genes. In addition, the telomeres allow the cells to divide in an orderly fashion, but only up to the Hayflick limits. In short, the bottom line is that telomeres prevent cells from mutations of the DNA, from senescence and from death.

Shortening of telomere length with age

Dr. Raphaele said that one of the important findings was that telomere length is shortening with age. Notably, he showed a slide similar to this. To clarify, this graph shows telomere length as a function of the lifespan in years. The telomere length is obtained by a blood test. This determines the length of the telomeres in white blood cells. At a young age it has a length of between 8 and 10 kb. kb stands for kilobase. A kilobase consists of 1,000 pairs of nucleic acid sequences. So, 10 kb means 10,000 pairs of nucleic acid sequences. Around the age of 80 people have much shorter telomeres, only 4 to 6 kb. There is an enzyme, called telomerase that can elongate telomeres by approximately 10%. But this may not be desirable as too much telomerase activation can also stimulate cancer growth.

Age changes telomere length

Dr. Raphaele explained further that a telomere loses about 100 base pairs per cell division. But there are other factors that shorten telomeres. Smoking, sedentary lifestyle, high blood pressure, stress and a low antioxidant status all can shorten telomeres. Certain congenital conditions can shorten telomeres by 28%. Dyskeratosis congenita is such a condition where 80% patients die by the age of 30 due to aplastic anemia. This is associated with bone marrow failure. 10% of these patients die from cancer. Apart from age, which shortens telomeres slowly, lifestyle factors are very important. A good lifestyle where you exercise regularly, you don’t smoke and you eat a healthy diet will slow down the shortening of your telomeres. Controlling your stress, sleeping enough hours per night and taking supplements also delays telomere shortening. Certain medications that control diabetes, high blood pressure or thyroid medication that treats hypothyroidism also delay telomere shortening.

Telomeres and shortened lifespan

Researchers could show that good lifestyle practices work by increasing telomerase to a certain degree. This results in lengthening of telomeres and translates into up to 10 years of increased life span. Jerry Shay, PhD said in 2011: “While the aging process is complex and certainly cannot be explained solely on the basis of telomere biology, there is a growing consensus that in some situations telomere biology and telomere tests may have important utility similar to cholesterol assays or blood pressure monitoring measurements.”

Telomeres are not just a biological clock inside our cells. They have a great influence on the function of mitochondria and on how many mitochondria multiply inside cells. This latter process is called mitochondrial biogenesis. In addition, telomeres regulate gene expression.

Chronic diseases associated with shortened telomeres

Here is a list of chronic diseases where all the patients have shortened telomeres.

  • High blood pressure
  • Hardening of the arteries (atherosclerosis)
  • Cancer
  • Chronic obstructive pulmonary disease (COPD)
  • Alzheimer’s disease
  • Diabetes and obesity
  • Chronic stress
  • Metabolic syndrome

Telomeres in cardiovascular disease

Telomere length was found to be shortened in those who developed a heart attack. Researchers compared the telomere length in coronary artery disease (CAD) patients to people with no history of heart attacks. In comparison to this normal group the heart attack victims had telomeres typical for people who are chronologically 11.3 years older than the healthy controls. The researchers calculated that people with telomere shortening had a 3-fold higher risk of coming down with a heart attack.

Telomere length enhancers

  1. Lifestyle changes can have positive effects on telomere length. Examples are smoking cessation, weight loss and stress reduction.
  2. Dietary changes: we know that fish oil (omega-3 fatty acids) supplements elongate telomeres as does a low-fat diet.
  3. Supplements like vitamin D3, antioxidants (vitamin C and E) and astragalus (TA-65) elongate telomeres as well. The astragalus supplement, TA-65 showed a significant elongation of telomeres after 12 months while controls lost telomere length.
  4. Exercise: in a 24-week experiment of care workers regular aerobic exercise increased the telomeres by 67.3 base pairs.
  5. Bioidentical hormone replacement in aging people: when hormones are missing after andropause and menopause, the natural hormones need replacing, or the telomeres are shortening.
  6. High cortisol levels cause telomere shortening.
  7. Human growth hormone elongates telomeres via telomerase activation.
  8. The fasting mimicking diet (FMD) was shown to extend life and telomeres as well.

Therapeutic rationale for telomere lengthening in CAD and AD

Patients with coronary artery disease (CAD) are at risk for developing heart attacks and other cardiovascular diseases. Here is an overview of many clinical trials that have been done in humans with CAD. It shows shortening of telomeres in these high-risk patients. But the review also shows that telomeres can lengthen by changing the risk factors of cardiovascular disease. Researchers were increasing the enzyme telomerase that indirectly lengthens telomeres. Both approaches prevent serious cardiovascular disease and increase life expectancy significantly. In severe cases of telomere shortening the physician can consider TERT gene therapy.

Alzheimer’s disease (AD) also is a condition where telomeres are shortened compared to normal controls. Time will tell whether TERT gene therapy is possible to prevent Alzheimer’s disease.

Telomeres are Important

Telomeres are Important

Conclusion

Telomeres are the caps of the chromosomes in our cells. In the past the word “telomere” appeared obscure and only scientists discussed this among themselves. Now we know that telomere shortening is often the reason for chronic illnesses like high blood pressure, hardening of the arteries (atherosclerosis), cancer, chronic obstructive pulmonary disease (COPD), Alzheimer’s disease, diabetes and obesity. Patients who have these conditions often have shortened telomeres in their white blood cells. Over the years we have learnt that lifestyle changes can have positive effects on telomere length. Smoking cessation, exercise, weight loss and stress reduction are elongating telomeres.

Additional factors elongating telomeres

In addition, supplements like antioxidants (vitamin C and E), vitamin D3 and astragalus root (TA-65) elongate telomeres as well. By elongating telomeres, a person can add 10 to 11 years of disease-free life to the normal life expectancy. Researchers showed that telomerase activation by human growth hormone increased telomere length without causing cancer. Dr. Thierry Hertoghe, an endocrinologist from Belgium spoke about HGH replacement in aging people on other occasions. He said that cautiously treating patients with low doses of HGH when blood tests showed deficiency, adds about two decades of life-expectancy to these patients’ lives.

May
20
2017

Prevention Of Telomere Shortening

Dr. Mark Rosenberg gave a talk on prevention of telomere shortening. This was presented at the 24th Annual World Congress on Anti-Aging Medicine (Dec. 9-11, 2016) in Las Vegas that I attended. The detailed title was: “The Clinical Value of Telomere Testing”.

What are telomeres?

Telomeres are the caps at the end of chromosomes. They are very important in the aging process. Prematurely shortened telomeres are linked closely to all major diseases like cardiovascular disease, cancer, diabetes and more. Telomeres are also a measure of the aging process. Aging occurs due to a decrease of the number of cells in organs and/or because of a lack of functioning of these organs. Telomeres get shortened every time a cell divides. But when the telomeres are used up, there comes a time when cells can no longer divide. These cells become senescent cells or they enter apoptosis (programmed cell death).

The senescent cells can become a problem when they get transformed into cancer cells and their telomeres lengthen again. These cancer cells divide rapidly and this can become the reason why cancer patients to die.

What is the significance of telomeres?

Telomere dysfunction is the first sign that the telomeres are getting shorter in a person compared to the average telomere length in a comparable age group. This is not only important for aging, but also has clinical implications. The shorter telomeres are, the higher the risk for cardiovascular disease. Telomere length also provides prognostic information about the mortality risk (risk of dying) with type 2 diabetes and for many cancers. Many physicians incorporate a telomere blood test into periodic health checks, if the patient can afford it.

Interventions that help telomere length

Here are a number of things we can do to lengthen our telomeres.

  1. Rosenberg mentioned that the strongest effect on telomere lengthening comes from caloric restriction and weight loss. 80 years ago they showed at the Cornell University that rats put on calorie restriction had a 30% increase in their mean and maximum lifespan. Many research papers have confirmed that the same is true in man and that the common denominator is telomere lengthening.
  2. Next are regular physical activity, meditation, reduction of alcohol consumption and stopping to smoke.
  3. Taking antioxidants and omega-3 fatty acids regularly will also lengthen telomeres.
  4. Improving one’s dietary pattern by adopting a Mediterranean type diet that contains cold-pressed, virgin olive oil.
  5. Telomerase activators. Here is some background on the TA-65 telomerase activator, which is based on Chinese medicine. A one year trial was completed with 250 units and 1000 units of TA-65 per day. The lower dose (250 units) showed effective telomere lengthening, while the placebo dose did not. The 1000 unit dose did not show statistical significance.

Should you wish to take TA-65, only take 250 units per day, not more.

Cancer and telomeres

There is a strong correlation between cancer and telomere shortening. When cells are at the brink of dying toward the end of their life cycle the telomeres get shorter and shorter. This is the point where the cells can turn malignant. Certain genetic abnormalities help the malignant transformation, like 11q or 17q deletions or a p53-dependent apoptosis response. Once cancer cells have established themselves they activate telomerase in 85% of cases. In the remaining 15% of cancer cases telomeres are activated through telomerase-independent mechanisms. Here are a few examples.

CLL

CLL stands for chronic lymphocytic leukemia. It is a disease of the aging population. At age 90 people’s bone marrow cells have a telomere length of only 50% of the length at birth. This is the reason that in older age CLL is more common. Researchers observed a population segment and found that the shorter telomeres were, the poorer the overall prognosis and overall survival for CLL was.

Lung cancer

Researchers examined the telomerase activity in patients with non-small cell lung cancer. When telomerase activity was present, the 5-year survival was only 55%. When telomerase activity was absent, the prognosis was 90% survival after 5 years.

Prostate cancer

  1. Prostate cancer risk correlated with telomere shortening in stromal cells. Men with shorter telomere length in stromal cells had a 266% higher risk of death compared to men with normal telomere length.
  2. Another study took blood samples and determined the telomere length in lymphocytes (the immune cells). Those men who came down with prostate cancer within a year after they had their blood sample, had short telomeres. The risk for prostate cancer in these patients was 355% higher than in the prostate cancer negative controls.

Yet another study looked at surgical tissue samples from 596 men that

Underwent surgery for clinically localized prostate cancer. Patients whose samples showed variable telomere lengths in prostate cancer cells and shorter telomeres compared to prostate samples with less variable telomere length and longer telomeres had a much poorer prognosis. They had 8-times the risk to progress to lethal prostate cancer. And they had 14-times the risk of dying from their prostate cancer.

Breast cancer

Breast cancer is diverse and consists of cases whose origins are genetic (BRCA1 and BRCA2), but there are also cases where the cancer is local or has a higher stage. In families with mutated BRCA1 and BRCA2 telomeres are significantly shorter than in spontaneous breast cancer. Increased telomerase activity in breast cancer cases is directly related to how invasive and aggressive the breast cancer is.

  1. In one study researchers analyzed blood leukocytes in 52 patients with breast cancer for telomere length  versus 47 control patients. Average telomere length was significantly shorter in patients with a more advanced stage of breast cancer than in early breast cancer. Mutated HER patients had the shortest telomeres. It follows from this that checking for the HER status and blood telomere testing adds to the knowledge of potential cancer development and prognosis.
  2. In patients with with larger breast tumors, more lymph node metastases and more vascular invasion the researchers found short telomere length of the cancer cells.
  3. More aggressive breast cancer cells have higher telomerase activity. More than 90% of triple negative breast cancers have short telomeres.

CNS disorders and telomeres

Dr. Rosenberg presented evidence for a correlation between shorter telomeres and the development of dementia. But dementias with Lewy bodies and Alzheimer’s disease are also linked to short leukocyte telomeres. The length of blood telomeres predicts how well stroke patients will do and how people with depression will respond to antidepressants.

Cardiovascular disease and telomeres

The renin-angiotensin-aldosterone system controls our blood pressure and keeps it constant. When this system is not stable, our blood pressure shoots up and causes cardiovascular disease. This is tough for the heart, as it has to pump harder against a higher-pressure gradient. A study of 1203 individuals was examining the connection between leukocyte telomere length and renin, aldosterone and angiotensin II activity. It concluded that oxidative stress and inflammatory responses affect the telomere length of leukocytes and that the more stress there is in the renin-angiotensin-aldosterone system, the more cardiovascular disease develops. The conclusion of the study was that the overall cardiovascular stress leads to shortening of leukocyte telomeres.

Prevention Of Telomere Shortening

Prevention Of Telomere Shortening

Conclusion

Telomere length testing from a simple blood test will become a more important test in the future as hopefully the cost comes down (currently about 300$). It can predict the general aging status by comparing a single case to the general telomere length of the public. But it can also predict the cancer risk, risk for mental disease and cognitive deficits (Alzheimer’s disease). In addition your cardiovascular status correlated globally with this test. What are the options for the patient, if the test comes back with short telomeres?

It allows you to change your lifestyle and adopt a healthy diet. You can exercise regularly, take antioxidants and meditate. There are even telomerase activators that are gradually becoming more known. They lengthen the telomeres. The cost of telomerase activators will likely still be a problem for some time. All in all telomere length tests are here to stay, but healthy lifestyle choices are the only tool for effective intervention at this point. This is good news: healthy lifestyle choices like non-smoking, exercise and avoiding non-processed foods are either free or have a reasonable price tag. Telomerase activators are big business and at this point not really affordable!