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

In patients with non-small cell lung cancer the telomerase activity was examined. 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. Telomere shortening in stromal cells was found to be associated with prostate cancer risk. 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 the blood sample was taken 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 that are genetically inherited (BRCA1 and BRCA2), but there are also cases where the cancer is local or more advanced (staging). 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. One study was shown where blood leukocytes were analyzed for telomere length in 52 patients with breast cancer 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. Short telomere length was associated with larger breast tumors, more lymph node metastases and more vascular invasion. 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 that shorter telomeres are associated with 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

Our blood pressure is kept constant through the renin-angiotensin-aldosterone system. 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 is also globally assessed with this test. What can be done, 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 effective intervention at this point is largely limited to healthy lifestyle choices. 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!

Dec
11
2016

Cancer Rates Increased In Women

A recent review of cancer rates worldwide shows that cancer rates increased in women. This by itself is alarming, but based on that data the rates likely will go up by 60% in the year 2030. The main reason is the smoking discrepancy among women and men. Men as a group have been smoking more than women. But women as a group are more and more embracing smoking. All of the negative health consequences of the last 3 decades for men are just starting to show now for women as well.

The World Health Organization explains it this way: in high-income countries like Australia, Canada, the US and Western Europe women smoke at nearly the same rate as men.

But in low and middle income countries women do not smoke as much as men do. For instance in China 61% of men are smokers, but only 4.2% of women are smoking. In Argentina 34% of men are currently smokers, which compares to 23% of women who smoke in this country.

When this gap will close, likely by the year 2030 women will have a whole host of diverse cancers, heart attacks and strokes caused by the smoking habit.

Some statistics and facts

High-income countries like Australia, Brazil, Canada, Israel and many northern and western European countries have a 5-year survival rate for breast cancer of 85%. In contrast the 5-year survival rates are 60% or less in low- and middle-income countries like South Africa, Mongolia, Algeria and India.

Cancer prevention measures can make a big difference later in life. Examples are hepatitis B vaccination, which will prevent liver cancer; vaccinating boys and girls against HPV, which will prevent cervical cancer in women; also having regular mammograms will detect breast cancer earlier and improve breast cancer survival rates.

Dr. Nestor Esnaola, surgical oncologist at Fox Chase Cancer Center at Temple University Hospital, Philadelphia, PA said that the cancer prevention methods just mentioned might not be available in developing countries. Instead of mammographies repeat breast self-examinations are more important there. Campaigns against smoking can be utilized in order to prevent cancer of the lungs, the throat and neck. And if colonoscopies are not available, stool samples can be tested for blood and hemoglobin to check for colon cancer.

Different cancer rates increased in women in different countries

There are different cancer types that make the top chart for different countries. For instance in 2012 breast cancer was on top of most countries worldwide as the number 2 killer behind heart attacks and strokes. But other cancers ranked fairly high as well as causes of death: colorectal, lung and cervical cancers.

Despite this trend there were other countries like China and North Korea that had a higher incidence of lung cancer rather than breast cancer. The cancer researchers stated that the reason for this is that the smoking rates are higher in these countries. As already pointed out in China more than ½ of the men smoke, but only a small minority of the women smoke. But women in China are exposed to high amounts of secondhand smoke in addition to environmental pollution, which still causes a lot of lung cancer in women who live in this environment.

In many African countries cervical cancer is very common. Women, who are HIV positive, have a 5-times higher rate of cervical cancer. Southern and eastern Africa where there are higher rates of HIV, have higher rates of cervical cancer.

More data about women’s cancer rates

The American Cancer Society has produced a report entitled “Global Burden of Cancer in women, current status, trends, and interventions”, which points out some interesting statistics.

The greatest numbers of cancer cases and deaths occur among women in Eastern Asia. The estimate for 2012 worldwide was for 1.7 million cancer cases and 1 million deaths in women. China dominated its region with 75% of all female cancer cases and deaths in the region. In North America cancer cases and deaths within the US comprise 90% of the region. The cancer cases and deaths in India make up about 65% of the region of South-Central Asia.

The top mortality rates are found in low to medium income countries, namely in Zimbabwe, Malawi, Kenya, Mongolia and Papua New Guinea.

The most frequently diagnosed cancers in women are breast, lung, and colorectal cancers in economically more developed countries. However, the statistics are different for less developed countries where the top three most diagnosed cancers are breast, cervix, and lung. Similarly the leading causes of cancer deaths for women in developed countries are lung, breast, and colorectal cancers. In developing countries the leading causes of cancer deaths for women is cancer of the breast, lung, and cervix.

Cancer frequencies for women in different countries

The American Cancer Society reports that breast cancer is the most common diagnosed cancer among women in 140 countries. Cervical cancer is most common in 39 countries, all of which are low to medium income countries. There are some countries where other cancer types are more common. For instance in China and North Korea lung cancer is more common among women, in Mongolia and Laos liver cancer, and in South Korea it is thyroid cancer.

The most common cause of death from cancer in women is breast cancer in 103 countries, cancer of the cervix in 43 countries and lung cancer in 27 countries. Other most common cancer deaths in women are in the following countries:

  • Stomach cancer: in Bhutan, Peru, El Salvador, Guatemala, and Tajikistan
  • Liver cancer: in Laos, Mongolia and The Gambia
  • Colorectal cancer: in Japan and Slovakia
  • Esophagus cancer: in Turkmenistan.

Prevention and early detection

Changing the risk factors could modify 20% of breast cancer mortality worldwide. Avoiding excess body weight, physical inactivity and reducing alcohol consumption could all significantly reduce breast cancer mortality. For instance, women with a body mass index of greater than 35.0 have a 1.6-fold higher risk of breast cancer and a 2.1-fold higher mortality rate from breast cancer than women with a body mass index of less than 25.0.

Regular breast cancer screening with mammography is another tool that will reduce breast cancer mortality as the cancer is diagnosed earlier and treated at an early stage where it can often be cured. The WHO recommends for those countries where mammography programs are established that screening should be done only every two years and only between the ages of 50-69 to avoid X-ray over exposure.

Early detection, like for any cancer is the key for successfully treating breast cancer. When the cancer is found early, surgical removal in healthy tissue (lumpectomy) often cures breast cancer. Unfortunately in low to medium income countries the cancer is often found too late, requires more invasive mastectomies and radiotherapy and has a lower survival rate than in developed countries.

Cervical cancer

Cervical cancer accounts for the 4th most frequently diagnosed cancer in the world. In 2012 there were 527,600 cases diagnosed worldwide and 265,700 deaths from cervical cancer occurred in the same year. 90% of cervical cancers occur in developing countries with India accounting for 25% of the total cases. The key in detecting cervical cancer is a regular screening program. In developed countries where this has been in place cervical cancer incidence has decreased by 80% in 4 decades. At the other end of the spectrum are countries like Uganda, Zimbabwe, and some countries of Central and Eastern Europe where cervical cancer rates have been climbing. The reason for the spread is that the human papillomavirus (HPV) is now more common and screening methods for cervical cancer are not in place. HPV 16 and 18 are the most common carcinogenic subtypes of the human papilloma viruses; they are responsible for 70% of cervical cancers worldwide. By vaccinating teenagers before they engage in sex is a powerful tool to interrupt the infectious spread of an important risk factor for cervical cancer.

Instead of the traditional Pap test from the past the new test that is used now is an HPV-DNA test, a cervical swab that will detect DNA from HPV directly. It is more sensitive than the traditional Pap test. If the HPV-DNA test is positive, the patient is sent to a gynecologist who will perform a colposcopy test, which is a microscopic exam of the cervix. The gynecologist can use several effective treatment methods like a loop electrosurgical excision procedure, laser ablation therapy, cryotherapy or conization for deeper cervical cancer lesions.

As with any cancer early detection and treatment is paramount with cervical cancer. In developed countries the 5-year survival rate is 60 to 70%. In India the 5-year survival rate is 46%.

Cancer of the lung

In 2012 there were 583,100 cases of lung cancer in women worldwide and 491,200 died from it. Lung cancer is the second leading cause of cancer death in women and the third most common cancer. The statistics of lung cancer reflect the tobacco epidemic. It takes about 20 to 30 years after widespread smoking begins in a country before the deadly statistics set in. The peak of the cancer epidemic and the heart attack rates occurs about 30 to 40 years following the peak of smoking in that population.

Lung cancer rates in women have lagged behind men, because women as a group have started smoking later. In places like Hong Kong, the United Kingdom,

Australia, and the United States women started smoking earlier, and they are in the process of declining their smoking habit or quitting. This is reflected in the new lung cancer cases and also in the lung cancer mortality rates. Sadly, in many countries of Europe and Latin America women started smoking much later and they are still increasing their lung cancer statistics and mortality rates. Lung cancer killed 1.1 million men and 0.5 million women worldwide in 2012. In addition it is estimated that there are 21,400 lung cancer deaths annually from second-hand smoke in non-smokers worldwide.

Beside smoking there are other risks causing lung cancer. The estimated risk for women to die in millions is: exposure to household air pollution, 1.6; outdoor air pollution, 1.4; second-hand smoke, 0.35; occupational risk factors, 0.10; and residential radon, 0.03.

Cancer Rates Increased In Women

Cancer Rates Increased In Women

Conclusion

Women are still in the midst of a global increase of cigarette smoking, which starts often with female teenagers. As long as the smoking rate goes up there will be more breast cancer, lung cancer and cervical cancer. The American Cancer Society provided a detailed review of various cancers and how they are still increasing worldwide, because nobody pays attention to preventative measures. A simple step to prevent cancer is to quit smoking. Another step is to engage in regular physical activity. Finally keeping your body mass index under 25.0 is a third step that can be done by adopting a Mediterranean diet.

There are several pockets within the developed countries where cancer rates are coming down, which is encouraging. The initial overview and the three examples given here, breast cancer, cervical cancer and lung cancer were thought to illustrate this complex topic.

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