Jul
18
2020

Key Factors for Centenarians

A study from Washington State University (WSU) showed some of the key factors for centenarians to survive. The publication of the study goes back to June 17, 2020. In general, it was common knowledge that genetics plays a role in 25% to 35% of centenarians for their survival. That is to say, the remainder is the result of lifestyle factors. It is important to realize that the environmental factors play a significant role in the survival of centenarians, said Rajan Bhardwaj, a second-year WSU medical student. He and his research team determined what allowed centenarians to reach an age of 100 or above. Briefly, they identified the following factors that were necessary.

Three factors identified by the Washington State University study

  • walkability of the neighbourhood, which encourages regular exercising
  • belonging to the higher socioeconomic class
  • a high percentage of working population in the neighborhood (a mixed population) was also important

In the discussion the authors of the WSU study said that “blue zones” of centenarians had been mentioned before in the literature. To clarify, these are areas in the world where more than the average of centenarians live. Dan Buettner used the term “blue zones” in a National Geographic article about where centenarians were located.

The blue zones

He wrote a book about the location of the 5 blue zones. Notably, they are located in Sardinia (Italy), the islands of Okinawa and a group of Seven Day Adventists in Loma Linda. California. In addition, the Nicoya Peninsula of Costa Rica, and the island of Icaria, Greece complete the 5 blue zones. Specifically, Dan Buettner described the following characteristics of the lifestyle of centenarians.

  • They engage in regular physical activity
  • Mostly eating a plant-based diet including legumes
  • Calorie intake is moderate
  • Moderate intake of alcohol, mostly wine
  • Having a purpose in life
  • Engaged in family life
  • Having an active spiritual life
  • Reducing stress
  • Engaged in social life

Other attributes of centenarians

Dr. Thierry Hertoghe gave a presentation in Las Vegas on Dec. 14, 2019 where he stated that centenarians are positive thinkers. This was at the 27th Annual World Congress on Anti-Aging Medicine. In particular, the topic of his talk was “Positive Psychological Attitudes of Centenarians “. Dr. Hertoghe is an endocrinologist in Belgium. He took an interest in people above the age of 100. These people, he felt, are special people with a very optimistic outlook on life. Dr. Hertoghe went on to say that centenarians have a will to live. Indeed, they adapt to changes; they have a sense of purpose, and they stay active.

More positive attributes of centenarians

Other psychological features, by the same token, show that they have a positive mood and they avoid stress and anxiety. Another key point is that they have self-determination. It must be remembered also that they are very sociable, have close family ties, love their relationships and often have a strong religious faith. In addition, there is a connection between their basic values, beliefs and spirituality. Truly, centenarians insist on their freedom and they have a feeling of youth. For one thing, centenarians have their own centenarian spirit where they can feel young or old.

In the following I am reviewing some of the details that Dr. Hertoghe gave.

The will to live

For one thing, it takes courage to grow old, and all centenarians have this. They say “Life is worth living”. Essentially, they have a certain resiliency in a world that has an obsession about youth. Despite negative experiences they had to overcome they do not give up and they enjoy life as much as they can. A Finnish study examined 400 individuals aged 75-90 and followed them for 10 years. Group 1 who wished to live less than 5 years had a mortality rate of 68%. Group 2 wished to live for 5-10 years. They had a mortality of 45.6%. The last group, group 3 wanted to live more than 10 years. Surprisingly, their mortality was only 33.3%. Be careful what you wish for!

Adaptability

In other words, this describes the capacity to overcome adversity and your ability to adjust. In a study of 7400 Chinese centenarians’ resilience to changes was measured with psychometric psychological tests. The majority of subjects did not qualify for being resilient. However, 9% of male centenarians and 6% of female centenarians had the resiliency where they qualified for high adaptability. This high resilience group had a 2%-4% lower mortality risk. They had a 36%-55% higher probability of not developing cognitive impairment. That is to say, they rated themselves to be in good health and having a “good life” satisfaction. These resilient centenarians had a 7%-12% higher probability of not developing a physical disability. In essence, these high resilient centenarians had no short-term health decline.

Remaining active

If a centenarian remains active and moves about several hours per day, the body functions are preserved. Anna Mary Robertson Moses who was known by her nickname “Grandma Moses” took up painting at age 78. She died at age 101 in 1961.

Positive emotions

One study of 54 Ashkenazi Jewish older adults (aged 98-107) compared those with positive emotions to those with negative emotions. The researchers noted that a positive attitude about life allowed centenarians to live longer.

A study involving 2282 Mexican Americans aged 65 to 99 showed that positive affect scores were a predictor for the following. Subjects with a high positive affect had a 52% lower probability of becoming physically disabled. They were 36% less likely than the negative controls to lose their walking speed. In addition, they were 47% less likely to die during the two-year observation period than their negative controls.

Nurses’ Health Study and Veterans Affairs Normative Aging Study

Two studies, the Nurses’ Health Study (NHS) and men from the Veterans Affairs Normative Aging Study measured optimism. The researchers found that those with the highest optimism scores had a 1.5-fold higher probability in women and 1.7-fold in men to survive to age 85. This was compared to a control with the lowest optimism scores. Dr. Hertoghe provided 19 more studies that showed the effects of positive emotions regarding long term survival. For brevity reasons I will not dwell on them here.

What is the centenarian spirit?

When people are older than 100 years, they often have a mix of humor and eccentricity; they express emotions openly and they are happy people. They accept the death of spouses, siblings and significant others.

By the way, humor has a strong predictive survivor value. In a study that researchers conducted over 15 years, there was a clear positive effect of humor regarding mortality. A sense of humor reduced the all-cause mortality by 48% in males. In women humor lowered mortality regarding cardiovascular disease by 73%. Humor reduced death due to infections in women by 83%. Men had a non-significant reduction of all‐cause mortality by 12% and a significant lower mortality due to infections by 74%. Dr. Hertoghe cited three more publications that showed the power of humor in reducing disease and disability.

The fasting mimicking diet helps you to reach a longer life

clinical trial with 100 subjects was undertaken by Dr. Longo and his research team. He measured markers after 3 cycles of a fasting mimicking diet for 5 days every month. They found that the FMD reduced aging markers, improved diabetes and reduced susceptibility for cancer and cardiovascular disease. In another publication Dr. Longo and co-authors describe how autoimmune diseases can be improved by the use the fasting mimicking diet for 5 days every month.

Another publication by Dr. Longo describes that “age-related disorders including diabetes, cardiovascular disease, cancers and neurological disorders such as Alzheimer’s disease, Parkinson’s disease and stroke” can be prevented by fasting mimicking diet for 5 days every month.

Even cancer prevention and cancer treatment can be helped by the fasting mimicking diet.  The FMD makes chemotherapy more tolerable.

Key Factors for Centenarians

Key Factors for Centenarians

Conclusion

As we reviewed the factors that lead to longevity, we learnt that engaging in regular moderate exercise is one of the key factors. But belonging to the higher socioeconomic class and living in a mixed neighborhood with people from all walks of life is also important. We also reviewed the blue zones according to Dan Buettner. Mostly eating a plant-based diet including legumes with moderate calorie restriction prolongs your life. Add to this moderate intake of alcohol, mostly wine, and having a purpose in life. Augment this further with being engaged in family life, having an active spiritual life and reducing your stress level.

Living longer is a matter of fulfilling these longevity factors

With all of this you are on your way to become a centenarian. A review by Dr. Hertoghe in a lecture given at an Anti-Aging Conference in Las Vegas in 2019 added more criteria centenarians have. He provided references regarding the will to live, being adaptable, remaining active and harboring positive emotions. The more of these factors you can adopt, the longer you will live. At the same time, you will avoid getting diseases like heart attacks, strokes or cancer, which leads to a longer and healthier life.

The above text contains parts of this blog. The part about the fasting mimicking diet was published here before.

Apr
25
2020

Exosomes can Regenerate Your Stem Cells

Dr. Douglas J. Spiel gave a talk on how exosomes can regenerate your stem cells. In essence, this was at the 27th Annual World Congress on Anti-Aging Medicine in Las Vegas from Dec. 13 to 15th, 2019. His original topic was: “Placental MSC Exosomes for Longevity and Chronic Disease”. Notably, MSC stands for “mesenchymal stem cells”. Dr. Spiel recommended this website to look at applications of exosome therapy.

Essentially, what scientist found is that certain factors from stem cells can activate your own stem cells to regenerate tissues that grow old. These factors are messenger RNA (mRNA) and micro RNA (miRNA), which come as tiny particles of 40‐100 nm.

Advantages of administering exosomes

To emphasize, exosomes can be given systemically as infusion, and they can regenerate your stem cells, if they are in need of treatment. They cross the blood brain barrier, so it is possible to treat brain diseases. That is to say, there is no first-pass removal in the lungs as it is with mesenchymal stem cells (MSC). The potency is related to the age of the donor and his/her stem cells. Notably, exosomes are easy to store, freeze and administer.

Exosomes influence the growth of target cells and promote regeneration. In addition, exosomes stimulate immunomodulation and have anti-inflammatory and anti-fibrotic properties. To clarify, the only limitations are that the strength of the exosomes is related to the age of the blood donor. The exosome fraction comes from mesenchymal stem cells. That is to say, it circulates in the plasma portion of the blood, which is obtained by spinning blood cells down in a centrifuge. To emphasize, exosomes can regenerate your stem cells.

Applications of exosomes for various clinical conditions

Joint inflammation

Mesenchymal stem cells are useful to treat arthritis. But it is important to realize that exosomes from mesenchymal stem cells are doing the same by stimulating the body’s own stem cells situated in the joints. In fact, several target cells have been identified that are stimulated by exosomes. These are chondrocytes, chondrocyte progenitor cells, cartilage-derived stem cells and synovium‐resident multipotent progenitor cells. In addition, other target cells are osteoblasts and osteoclasts in resident MSC within the subchondral bone and chondrogenic cells in the knee joint.

Disc degeneration  

Degenerative intervertebral discs respond to exosome treatments. The IL1 beta cytokine is involved in intervertebral disc degeneration. Exosomes inactivate these cytokines and have antioxidant and anti-inflammatory effects. Exosomes are not all the same. Different sub-fractions were isolated that have anti-inflammatory, immune-stimulating, antioxidant and other effects on the body.

Aging research

Researchers were able to pinpoint aging to various factors that contribute to premature aging. To clarify, when there is a decrease of catabolic processes and an increase of anabolic processes, an older person can combat premature senescence. Another key point, aging is also linked to redox homeostasis. Simply put, oxygenation processes in the body need to be balanced by reduction processes. This keeps the body in a healthy state. ADP/NADH production can be stimulated by exosomes.

Longevity comes from good lifestyles

With the use of exosomes, the aging process slows down, as oxidative stress is neutralized, damaged mitochondria are removed and cellular debris as well. That is to say, this improves inflammation and premature aging.

As has been noted, in the past 200 years life expectancy has doubled in most countries. 4 areas where longevity is particularly common are: Okinawa, Japan; Sardinia, Italy; Nicoya, Costa Rica and Loma Linda, USA. Only 7% of longevity stems from genetic factors, the rest is from lifestyles we adopt. In the final analysis, people who die prematurely followed a very poor lifestyle causing them to develop diseases, which ultimately killed them.

Clinical diseases from aging

Ultimately, advanced aging puts you at risk of getting cardiovascular disease (heart attacks and strokes), cancer and neurodegenerative diseases (Alzheimer’s disease, Parkinson’s disease). From the third decade onwards, there is the risk of bone loss, which causes osteoporosis. As has been noted, loss of cartilage causes osteoarthritis. Loss of muscle strength and muscle mass is called sarcopenia. With aging there is often an accumulation of abdominal fat. Hormones are disbalanced. Blood pressure is often elevated and blood lipids as well. Insulin resistance can develop and the blood vessels become stiffer. This causes heart attacks and strokes.

The details of the aging process are much more complicated than originally thought of. There is a combination of aging of the DNA, mitochondrial aging, stem cell exhaustion and a change of intercellular communication due to dysregulated endocrine signalling. In addition, there is a decline of the immune system and epigenetic factors that can turn off longevity genes.

Oxidative stress as a cause of premature aging

Dr. Spiel pointed out that reactive oxidative species (also known as free radicals) cause damage to mitochondria and mitochondrial DNA. But we need the energy from the mitochondria for a comfortable life. In essence, antioxidants can neutralize free radicals. Age-related conditions due to oxidative stress are: cardiovascular disease, chronic kidney disease and type 2 diabetes, chronic obstructive pulmonary disease, cancer, neurodegenerative disease, frailty and sarcopenia. Surely, both reactive oxygen and reactive nitrogen are free radicals. They have one or more unpaired electrons and all aerobic body cells produce them. Reactive oxygen and nitrogen species (RONS) cause oxidative damage to our cells and contribute to the development the diseases just mentioned.

Antioxidants help to prevent diseases

But antioxidants can contain these free radicals in various ways. The body has five built-in enzymatic ways to protect itself and five non-enzymatic ways (bilirubin, vitamin E, beta-carotene, albumin and uric acid). In addition, there are antioxidants that a person can take as supplements to inactivate RONS. These are: vitamin C and E; phenolic antioxidants like resveratrol, phenolic acids, flavonoids, oil lecithin, selenium, zinc and drugs like acetylcysteine.

Without control of the oxidative stress RONS can lead to cellular senescence and chronic inflammation. This leads to a vicious cycle where chronic oxidative stress and inflammation feed on each other leading to premature diseases.

Causation of several diseases

As we age, the body reduces the inborn antioxidant enzymes (superoxide dismutase and glutathione peroxidase). Before we can understand how to live longer, we need to be aware what happens in various health scenarios as follows.

  • The lack of inborn antioxidant enzymes leads to vascular endothelial dysfunction, high blood pressure and premature hardening of the arteries. This can become a precursor to heart attacks and strokes.
  • Elevated blood sugar in the case of type 2 diabetes leads to increased sugar concentration of body cells and formation of free radicals.
  • Oxidants from cigarette smoke activate macrophages and epithelial cells to produce inflammatory cytokines. Continued smoking releases proteases in the process that break down connective tissue and cause emphysema and COPD.

There are more diseases

  • Chronic kidney disease comes from oxidative stress affecting the filter units of the kidney, called glomeruli. With a lack of blood supply to the kidneys secondary high blood pressure develops and endothelial dysfunction. It also leads to chronic inflammation.
  • In the brain oxidative stress leads to cognitive impairment and dementia.
  • Oxidative stress and chronic inflammation are important ingredients for the development of cancer. RONS and cytokines release NF-kB, which activates cancer genes. RONS can also directly attack the DNA of cells and cause cancer through carcinogenesis.
  • Sarcopenia and frailty come from the action of RONS on the skeletal muscles. In old age there are less inborn antioxidants available. This leads to decreased muscle quantity or sarcopenia. Eventually frailty results with the risk of falls and fractures. 

Preventative measures for slowing the aging process

There is a number of steps that in combination help to slow the aging process.

  • A Mediterranean diet combined with a fasting mimicking diet or other calorie restricted diet
  • Regular physical activity
  • Cognitive training
  • Vitamin D3 supplementation
  • Reducing your risk to develop vascular disease
  • Certain drugs turn on the longevity gene (metformin, rifampin)
  • Spiel warned that due to limited compliance and variable response these steps alone may not be enough to prevent age-related problems

How to live longer

It is important to recognize the importance of antioxidants to counteract the development of these diseases. As already mentioned, the following counter the effect of free radicals: vitamin C and E; phenolic antioxidants like resveratrol, phenolic acids, flavonoids, oil lecithin, selenium, zinc and drugs like acetylcysteine. Mesenchymal stem cells can also stop the action of free radicals. In addition, exosomes, which (products of mesenchymal stem cells) do the same. Mitochondria, the power houses within the cells, create energy, but also release free radicals. In his clinic Dr. Spiel administers intravenous exosomes to counter the oxidative stress. Numerous studies linked mitochondrial dysfunction to various age-related diseases. There are markers in blood tests that the physician can order to analyze malfunctions in the body. Dr. Spiel showed 4 slides that contained a lot of medical information that is too technical. I omitted it for this review.

Intravenous infusions of exosomes

The important thing to remember is that epigenetics can be changed by exosome infusion and lifestyle changes mentioned above. Dr. Spiel said that generally he uses 15 ml of exosomes by intravenous infusion every 12 weeks for longevity and performance enhancement. This treats conditions like infertility, osteoporosis, osteopenia, heart, liver and kidney weaknesses. Here is the dosing for intravenous exosomes by weight:

20-50 lb: 5 ml; 50-90 lb: 10ml; more than 90 lb: 15 ml; more than 220 lb: 20 ml. Unfortunately, one exosome treatment costs between 500.00 and 922.00 USD, an amount that most people cannot afford.

Contraindication to the use of stem cells or exosome therapy

It is important to realize that a person who has cancer should not receive either mesenchymal stem cells or exosomes. Indeed, exosomes do not differentiate between cancer cells and healthy cells, but stimulate cell division. For the same reason people with myeloproliferative disease (sickle cell anemia, bone marrow dysplasia) should also not receive exosomes. To clarify, other conditions where the physician will not order exosomes are primary pulmonary hypertension, acute bacterial infection or an immune-compromised state. In addition, macular degeneration with neovascularization is also a condition where the health professional does not administer exosomes.

Exosomes can Regenerate Your Stem Cells

Exosomes can Regenerate Your Stem Cells

Conclusion

Dr. Douglas J. Spiel gave a talk on how exosomes can regenerate your stem cells. Specifically, this was at the 27th Annual World Congress on Anti-Aging Medicine in Las Vegas from Dec. 13 to 15th, 2019. Dr. Spiel explained how disease processes age our organs. Reactive oxygen and nitrogen species (RONS) cause oxidative damage to our cells and contribute to the development the diseases. This involves the mitochondria in the cells as well. The good news is that a healthy lifestyle can counter these damaging processes to a certain extent. But it takes another step to re-establish the balance of our cells, exosome infusions. Exosomes are tiny particles that are shed by stem cells and that circulate in the blood. They can reenergize stem cells that are ailing to become functional again.

Expensive exosome infusions

He recommended an infusion with exosomes every 12 weeks for maintenance of good health and as a “fountain of youth”. Obviously, there are some limitations. As mentioned, it is not suitable for all patients, like cancer patients, patients with sickle cell anemia, acute bacterial infections or pulmonary hypertension. In addition, it is also not a treatment which many patients will seek out as the cost is prohibitive. One exosome treatment cost between 500.00 and 922.00 USD, an amount that most people cannot afford.

Mar
28
2020

Fasting Can Prevent Cardiovascular Diseases

Dr. Joel Kahn gave a lecture in Las Vegas in which he explained that fasting can prevent cardiovascular diseases. Dr. Kahn is a Clinical Professor of Medicine at Wayne State University School of Medicine. He spoke at the 27th Annual World Congress on Anti-Aging Medicine in Las Vegas. The conference took place from Dec. 13 to 15th, 2019.

According to the CDC cardiovascular diseases like heart attacks and strokes are hitting the middle age adults in large numbers. Part of the problem is obesity and diabetes, both of which cause an increase of cardiovascular diseases. Heart attacks, strokes, heart failure and other related cardiovascular conditions caused 2.2 million hospitalizations in the US in 2016. This resulted in 415,000 deaths and a health care cost of $32.7 billion.

Fasting can improve the risk for cardiovascular disease

Dr. Kahn asked whether fasting can reduce the aging pathways, build up resilience and protect the heart from aging and heart disease. In a few words: eat less, live more! He showed with slides that fasting can indeed do that. One heart catheterization study showed that a fasting group had only 64% coronary artery disease compared to a non-fasting control group with 76%.

Another study showed that fasting patients had only 10.3% diabetes compared to controls with 22.0%. With heart catheterization 63.2% of fasting patients had cardiovascular disease while 75.0% of non-fasting control patients did have lesions in their coronary arteries.

Animal experiments confirmed that fasting had beneficial effects on heart health as well. In rats, researchers showed that fasting reduced infarct size and inflammation. It also preserved left ventricular function. With mice fasting produced less inflammatory response and less tissue damage.

Alternate day fasting shows benefit in clinical human trial

A 2019 publication reported about a 4-week randomized clinical trial on 60 healthy non-obese human subjects. The effect of alternate day fasting was compared to controls. On average there was a 37% calorie reduction in the alternate fasting group. The fasting group had improved fat mass, improved fat-to-lean ratio and cardiovascular markers. There was a reduction of age-associated inflammatory markers and low-density lipoprotein.

Fasting mimicking diet

A newer form of fasting is the fasting mimicking diet (FMD), which was invented and researched in depth by Dr. Valter Longo. Both animal experiments as well as human trials have shown that the FMD is safe and effective. It can be followed 5 days out of every month and will lead to some weight loss, an increase of telomeres, stem cells and lowered inflammatory markers.

My own experience with the fasting mimicking diet

My wife and I heard about the FMD from Dr. Longo when he spoke about it at the 2017 Anti-Aging Conference in Las Vegas. We immediately started the FMD in December of 2017 and have done it every month for 5 days since. But we never ordered the expensive meal kit. Instead, we calculated calories and use regular food to do the calorie-restricted diet. We eat 600 to 700 calories every day during the FMD days. In between we have unrestricted calories, but we noticed that we are more careful about our meal choices. I find that the result of the FMD is more energy, an improved sleep pattern and an easier way to keep my body-mass index in the 21.0 to 22.0 range. Here is a description of the effects of the FMD.

Use of FMD in high-risk patients

Dr. Khan said that the FMD is an ideal diet that the high-risk population of the US should use. 34% of the US population has a compromised metabolic condition. They are obese and at a high risk to develop diabetes. But on the FMD they gradually lose abdominal obesity, lower their cholesterol and triglycerides levels, which otherwise causes a high risk for heart attacks and strokes. The fasting blood sugar is lowering reducing the risk to get diabetes. The systolic and diastolic blood pressure comes down. And the C-reactive protein, which is a general inflammatory marker, becomes lower.

In non-obese patients the main effect of the FMD is a stimulation of stem cell release and telomere elongation. This postpones the aging process and with it delays the onset of cardiovascular diseases.

Fasting Can Prevent Cardiovascular Diseases

Fasting Can Prevent Cardiovascular Diseases

Conclusion

Dr. Joel Kahn gave a lecture at a Las Vegas conference that fasting can prevent cardiovascular diseases. He compared alternate day fasting with the fasting mimicking diet (FMD). The FMD was more effective in reducing danger markers, abdominal girth measurements and blood markers of cardiovascular diseases. Ultimately, he said, it was easier to follow an FMD where you only reduce your calorie intake to 600 to 700 calories per day for 5 days in one month. In those who are wanting to do this just for good health, the FMD increases stem cells and elongates telomeres. This postpones the aging process and keeps a person younger for longer. At the same time, it delays the onset of cardiovascular diseases.

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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.

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Feb
22
2020

Clinical Applications of the Fasting Mimicking Diet

Dr. Kurt Hong, professor of clinical medicine spoke about clinical applications of the fasting mimicking diet in Las Vegas. This was at the 27th Annual World Congress on Anti-Aging Medicine on Dec. 14, 2019. Although he spoke on various forms of fasting, he concluded that the fasting mimicking diet had the best results and was most consumer-friendly.

How we age

Dr. Hong reviewed the processes of aging. We age, because our cells experience oxidative damage and our telomeres (the end caps of our chromosomes) get shorter in time. We also age, because there are genetic mutations in our cells’ DNA and our mitochondria are aging as well. The mitochondria are the small energy packages inside the cells that give us energy. When people age, they have lost mitochondria, there is less energy that the body makes out of food and we feel chronically tired.

Above the age of 65 we are also likely to develop diseases of various organs:

  • Heart disease: 31%
  • Cancer: 24%
  • Chronic lung disease (lower respiratory disease): 21%
  • Alzheimer’s disease: 13%
  • Diabetes: 11%

Women are generally healthier than men and their life expectation is 4 to 5 years longer than that of men.

Cellular and molecular aging

Longevity researchers have done mouse experiments and human clinical trials for decades. Dr. Hong asked the question: how much longer could humans live, if we could cure cancer, heart disease, stroke and diabetes? The answer is: 13 years. But if we transfer the animal data to humans it should be 30 years of longer life. Why is there such a discrepancy? The answer is that it is easy to force good lifestyles onto animals, but humans are resistant to changes. Humans have their habits; they like to continue to smoke and eat fast food instead of switching to a healthier Mediterranean diet. Humans also resist a regular exercise program. And they do not want to hear that they should replace missing hormones with bioidentical ones. The result is that we humans will prolong our lives only by less than 50% of what we could achieve.

The concept of intermittent fasting

Dr. Hong stated, that ten thousand years ago, people did not always have enough food to eat. They were forced to intermittently fast. That did not mean that they had long life expectancies, as there was no cure for any disease. But one fact was true: the body learnt to rejuvenate itself during periods of fasting. And these longevity genes are still present in our genes. But they will only help us when we actually fast for some periods of time.

Dr. Hong reviewed what kind of fasting methods are available.

Prolonged fasting and juice fasting are not among the options. With prolonged fasting electrolyte disturbances become an issue. Juice fasting does not remove enough calories and nutrients. This, however is needed to allow the body to stimulate the longevity genes.

How fasting diets work

Dr. Hong explained that there are essentially 5 fasting diets that are effective in regulating the key nutrient sensitive pathways of IGF-1, TOR and PKA. This increases cellular protection and maintenance. It also increases activation of stress resistance pathways and removes and replaces damaged and dysfunctional cells. Finally, a fasting diet also reduces inflammation, which is often the start of disease.

A review of the 5 fasting diets

Time-restricted eating (TRE)

With TRE the person fasts for 12 to 16 hours every day. The person restricts the daily food consumption to a 4- to 12-hour window. The disadvantage is that this fast is done every day. The period of fasting may not be long enough to change the metabolism, where the above-mentioned effects take place.

Alternate-day fasting  

This is a 24-hour fast every other day with a 1:1 day eating-fasting cycle. This does not appear to be physiological and is disruptive with regard to social activities.

5:2 intermittent fasting

With this fast you fast for 2 days every week. With this 2:5 eating-fasting cycle the person fasts for 2 days every week; the other 5 days you eat as much as you desire.

Although this is effective, it can be quite disruptive to your lifestyle.

Periodic fasting

You fast for 48 to 72 hours every couple of months. This fast is socially more acceptable. It is not that often, just a couple of times in a year. The question remains whether it is effective in changing the metabolism to trigger the effects mentioned above.

Fasting-mimicking diet (FMD)

The original suggestion by Dr. Longo, the inventor of the FMD was that you should fast for 5 days once every month. Since then he has modified it and said that you can achieve similar metabolic changes, if you only fast for 3 days and do this a couple of times per year. I have done the FMD since December 2017 and I adhere to the original schedule of doing the FMD monthly for 5 days. This has provided me with more energy. It is easier to keep my body mass index in the 21.0 to 22.0 range. Dr. Hong explained that the FMD allows you to eat, but it tricks the body into acting like you are fasting. Because you are eating 500 to 600 calories per day, you are getting some fluid and nutrients, so the hunger pangs are tolerable.

More details about the FMD

Here is Dr. Hong’s summary about the FMD: “The stomach sees food, while the cells see fasting”. Dr. Hong said that the FMD is the most user-friendly method of fasting. It also has had the most scientific studies to validate that it is indeed working. Poorly functioning mitochondria and misfolded proteins are removed by a process of phagocytosis. The FMD reduces heart disease, cancer, and neurodegenerative disorders. Stem cell production also gets a boost. This promotes cell regeneration and reduces risk factors of premature aging.

Publication on the effectiveness of the FMD

A publication came out in 2017 reporting about the findings of a clinical trial regarding the FMD.

Researchers followed markers of aging, diabetes, cancer and cardiovascular disease in 100 volunteers. They underwent a FMD for 5 days on 3 consecutive months. The results were astounding. The body mass index, the fasting blood sugar level, triglycerides, total and LDL cholesterol and the CRP were all lower. CRP stands for C-reactive protein, which measures the degree of inflammation in the body. The blood pressure was also lower. Overall the 5-day FMD was a safe method with no side effects. The FMD reduced markers and risk factors of aging and age-related diseases. In doing so it prolongs life by reducing the likelihood of coming down with disease.

Who should abstain from fasting?

Dr. Hong mentioned that the FMD is not for everybody. Pregnant women should refrain from going on it, also type 1 and type 2 insulin dependent diabetics. Anybody who has a sign of an active infection (coughing, having a fever or diarrhea) should be excluded. Other exclusions are people who are underweight (BMI less than 18.5) or are malnourished (protein deficiency). Patients with heart failure and advanced kidney or liver disease should not take part in a fasting program.

Autoimmune diseases and FMD

The myelin sheath around the axon of nerve cells in the central nervous system are supported by oligodendrocytes. In multiple sclerosis (MS) patients T lymphocytes activate macrophages and B cells to produce autoantibodies. They destroy oligodendrocytes breaking down the insulating barrier of the myelin sheath. In MS patients the broken-down myelin sheath suppresses the electrical impulses transmitted through the nerve fibers. The FMD led to clinical improvements.

In a pilot study intermittent fasting changed the gut flora into a healthier flora.

This triggered the immune system in the gut to make less inflammatory T cells producing the IL-17 cytokines. There was also an increase in regulatory T helper cells.

Inflammatory bowel disease (IBM) can be improved with several courses of FMD. As the authors showed, intestinal inflammation improved with FMD. The intestinal gut flora improved with the FMD and it promoted intestinal regeneration.

Reversal of physical and functional decline

The fasting mimicking diet (FMD) has a variety of effects on the human body. Dr. Hong showed a slide where we could see that ketone bodies, cortisol and ghrelin levels are increased in the blood. At the same time glucose, insulin, leptin and IGF-1 levels are reduced. In addition, triglycerides and LDL levels are getting lower. Inflammatory markers including the C-reactive protein (CRP) are reduced as well.

Effects of the FMD on various organs in the body

A look at all of the organs shows that in the liver the ketone body production and insulin sensitivity are up. Glycogen production in the liver as well as the liver size are down.

The intestines produce ketone bodies. In the skeletal muscles the insulin sensitivity is increased, while the muscle structure and function are improved. In the brain the hunger feeling increases the release of neurotropic factors including the neuropeptide Y. Cognitive function and stress resistance increase with the FMD. The FMD reduces inflammation and oxidative stress in the brain. With respect to the cardiovascular system the heart rate drops down and blood pressure gets lower. The insulin production in the pancreas is reduced.

Fatty tissue

In fatty tissue lipolysis is up and also the production of adiponectin. This is a protein hormone involved in glucose and fatty acid metabolism. Insulin sensitivity with the FMD is also increased. On the other hand, the FMD reduces fat mass, leptin production and inflammation.

The FMD is the solution to preventing disease and prolonging your life

All of these effects lead to a reversal of physiologic and functional declines. Age-related metabolic diseases like type 2 diabetes are postponed or eliminated. The FMD prevents neuro-cognitive decline like Alzheimer’s disease. In addition, the risk of developing cancer is getting lower. In summary, the FMD improves the health-span, quality of life and can prepare you for a long life.

Clinical Applications of the Fasting Mimicking Diet

Clinical Applications of the Fasting Mimicking Diet

Conclusion

Dr. Kurt Hong is a professor of clinical medicine at UCLA. He gave a talk at the 27th Annual World Congress on Anti-Aging Medicine in Las Vegas on Dec. 14, 2019. He discussed what we could do to help patients with various autoimmune diseases like multiple sclerosis, rheumatoid arthritis and inflammatory bowel disease. It turns out that the fasting mimicking diet (FMD) is the best solution to reduce inflammation and modify  the autoimmune response from aggressive T lymphocytes. With the FMD you consume only 500 to 600 calories per day for 5 days every month. The rest of the days of the month you eat a healthy Mediterranean-type diet.

Fasting mimicking diet, the best way to treat autoimmune diseases

Dr. Hong explained in detail what cellular mechanisms are at work to achieve the modification of the immune system in autoimmune diseases. The FMD is also the solution to slow down aging in healthy people. Dr. Hong discussed clinical applications of the fasting mimicking diet fort autoimmune diseases. It is easier to prevent disease than it is to cure an illness. The FMD is an easier way, because you don’t fast completely, you only reduce your food intake to the bare minimum, but your body “thinks” that you are fasting.

Ultimately, this approach does take some effort, and it does take time to familiarize yourself with it. If patients do it for the first time, they will experience some hunger, the first and second day tend to be a hurdle! Once you make it part of a health routine on a regular basis, it is a lot easier.

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Feb
15
2020

Rheumatoid Arthritis Treatment by Regenerative Medicine

Dr. David Lans gave a talk at a conference in Las Vegas about rheumatoid arthritis treatment by regenerative medicine. This was at the 27th Annual World Congress on Anti-Aging Medicine in Las Vegas from Dec. 13 to 15th, 2019. The full title of his presentation was “Rheumatoid Arthritis, A Regenerative Medicine Approach”.

Dr. Lans is a rheumatologist and Assistant Clinical Professor of Medicine at the New York Presbyterian Lawrence Hospital, Bronxville, NY.

Introduction

Rheumatoid arthritis is a worldwide immune disorder. About 1% of the general population suffer of this illness with a female to male ratio of 3:1. Typically it can affect  the synovial membranes of all joints. To clarify, the presentation is usually symmetrical, but in 40% of all cases this systemic inflammatory disease can also involve other tissues and organs. 70% of cases have a positive rheumatoid factor (RF) in blood tests. However, a newer, more specific blood test for rheumatoid arthritis is anti-cyclic citrullinated peptide (anti-CCP). Symptoms of rheumatoid arthritis are anemia, fatigue, malaise, joint pain and joint stiffness. Inflammatory blood markers are positive.

Causes of rheumatoid arthritis

Genetic causes play an important role in the causation of rheumatoid arthritis. Over 100 genes  can increase due to genetics. Twin studies showed that the concordance rate to develop RA is only 15-20%. Certainly, this means that in order to develop RA you need a double hit: the genetic vulnerability for RA and also an environmental triggering factor. Meanwhile, here is a list of environmental risk factors:

  • Smoking
  • Gum disease (chronic gingivitis)
  • Any chronic infection
  • Dysbiosis in the gut
  • Environmental toxins
  • Heavy metal toxicity
  • Poor diet and nutrition

In other words, the common denominator to all of these environmental risk factors is the disruption of the mucosal integrity. In fact, this starts the process of chronic inflammation and autoantibodies (like RF and anti-CCP) resulting in chronic synovitis.

How inflammation travels from mucosal surfaces to the synovium of joints

Inflammation in gums, lungs or gut can travel via the blood and the lymphatic system into periarticular bone. This leads to bone and cartilage damage. Consequently, the bone destruction leads to chronic synovitis. To emphasize, Dr. Lans said that no patient with rheumatoid arthritis will develop symptoms of RA unless the autoantibodies have developed. In the same vein, there is a distinct preclinical period of RA with positive blood tests for RA, but absent clinical symptoms.

Prevention of synovitis through a preventative program

It is important to realize that because of this time relationship there is room for a preventative program where patients are taught the importance of dental hygiene. Another key point is that good health habits and nutrition are also important for prevention. When patients develop early-onset RA, the following measures often help to alleviate the development of symptoms: anti-inflammatory diet, stress management, intermittent fasting, a gut healing program, nutraceuticals like vitamin D3 and fish oil. Herbal therapies are also important like curcumin, Boswellia serrata, devil’s claw, ginger, Ashwagandha and others.

Conventional medicine approach versus the regenerative medical approach

To explain, the conventional treatment approach of rheumatoid arthritis is to induce a disease remission with drugs. To this effect doctors use anti-inflammatory drugs like ANSAIDs, disease modifying anti-rheumatic drugs (DMARDs). For example, drugs like methotrexate and sulfosalazine belong into this category. Unfortunately, the conventional drugs have many serious side effects that often make the rheumatoid arthritis patient’s condition worse.

In contrast, the integrative medicine approach to rheumatoid arthritis is to use dietary measures to reduce the inflammation. The fasting mimicking diet is able to reduce the severity of the inflammation in RA patients.

Other authors described the use of the Mediterranean diet to reduce inflammation. In addition, there are a number of regenerative methods that help improve the condition of RA patients.

Regenerative medical treatments for RA patients

Significantly, platelet rich plasma (PRP), peptides, stem cell therapy and exosomes are some of the modalities that show promise. (I’ll explain the meaning of exosomes later.) In addition, red light therapy and low-level laser therapy can help joint synovitis.

PRP provides growth factors to repair damaged tissues and is anti-inflammatory. Peptides consist of short chains of amino acids that have anti-inflammatory effects and promote healing of damaged tissues. Thymosin-alpha 1, Thymosin-beta 4, BPC-157, Melanotan II and FOXO4-DRI are examples of peptides used in patients. Special blood tests are used to monitor whether the treatment of RA is successful. These tests are: C-reactive protein, sedimentation rate (ESR) and Vectra. Vectra measures 12 protein markers that are important in RA.

More info about peptide therapy

Researchers noticed that peptides are very safe, but they are also very effective. HAP-1 seems to bind to synovial surfaces. RDG peptides work closely together with integrin-binding proteins. Together they have an anti-inflammatory effect in rheumatoid arthritis. They are capable of blocking both the inflammatory and autoimmune components of rheumatoid arthritis. Thymosin-alpha 1 is a peptide with powerful effects as an immune and inflammation modulator. Thymosin-beta 4 is promoting tissue healing. BPC-157 is a peptide with 15 amino acids. It helps with the regeneration of tissue after damage.

Melanotan II is a synthetic peptide derived from melanocortin, a pituitary hormone. It helps to suppress cytokine-meditated inflammation.

FOXO4-DRI is a peptide that stimulates the removal of senescent cells. Because of this it is called a senolytic. Researchers are still investigating FOXO4-DRI in humans and for the tissue repair effect in rheumatoid arthritis patients.

The use of stem cells in RA therapy

Another biological remedy for treating RA patients is the use of mesenchymal stem cells. In 2013 rheumatoid patients received umbilical cord stem cells to study the effect of stem cells. The clinical trial consisted of 172 patients. In the trial disease modifying anti-rheumatic drugs plus placebo were compared to disease modifying anti-rheumatic drugs plus umbilical cord stem cells (treatment group). In the treatment group inflammatory cytokines were reduced and regulatory T cells were increased. Improvement was assessed with objective clinical measures and blood tests. The improvement lasted between 3 and 6 months.

Exosome therapy from mesenchymal stem cells 

Many of the effects of stem cells are explainable by so-called exosomes. They are cell particles shed by stem cells. They contain signalling proteins (integrins), messenger RNA and many other healing substances. The bioactive effects are very diverse. Exosomes are bactericidal, antifungal, stimulate angiogenesis and stimulate tissue regeneration. They are also anti-apoptosis, anti-tumoral, anti-fibrosis, stimulate immunomodulation and cause chemoattraction.

What does that mean clinically? Exosomes suppress the release of inflammatory cytokines. Anti-inflammatory cytokines (like transforming growth factor beta or TGF-beta) are increased. Exosomes reduce the Th17 cells (T helper cells that produce the inflammatory cytokine IL-17). They also promote osteochondral regeneration, which is important for joint healing in the treatment of RA patients.

Treatment of RA using the integrative and regenerative medicine approach

  1. The physician assesses all affected joints and orders blood tests to check the inflammatory status.
  2. Identify the triggers that perpetuate the RA disease. Typically there are gut dysbiosis issues that need treatment. Sleep hygiene and stress issues require modification.
  3. Assess the need for disease modifying anti-rheumatic drugs (DMARDs); these are drugs like methotrexate, sulfosalazine and others.
  4. Peptide protocol: BPC-157: 300 micrograms once or twice daily IV; Thymosin alpha: 300 micrograms once or twice daily IV; Thymosin beta: 100 to 300 micrograms once daily IV, limit to 3-month cycle.
  5. Mesenchymal stem cell therapy and exosomes.
Rheumatoid Arthritis Treatment by Regenerative Medicine

Rheumatoid Arthritis Treatment by Regenerative Medicine

Conclusion

Rheumatoid arthritis is a common autoimmune disease, which leaves the patient disabled, if she receives no treatment for it. Conventional rheumatologist protocols treat the inflammation with various drugs, but they cause a lot of side effects.

There is an emergence of regenerative therapies that may be able to help treat the inflammation of the rheumatoid arthritis patient with less side effects. At the same time these treatments can also help to repair the damaged tissues. There is a great need for more clinical studies. Current human data are limited. Safe options to treat RA patients are mesenchymal stem cell therapy, exosome treatment and peptide therapies. The approach of the physician depends on the clinical stage the patient is in. It is common sense that early diagnosis and treatment will have better results. Also, an integrative approach has the best chance to help the patient with the least side-effects.

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Jan
04
2020

Preserving Youthful Power

Dr. Christopher W. Shade (PH.D.) presented a lecture in Las Vegas on Dec.13, 2019 talking about preserving youthful power. The presentation was at the 27th Annual World Congress on Anti-Aging Medicine and his title was “Building Youthful NAD+ Power with Precursors, Sirtuin-Activating Compounds, and Methylation support”.

In the first place, nicotinamide adenine dinucleotide (NAD+) is a signalling molecule between the DNA of the nucleus of cells and the energy producing mitochondria that reside in the cells. The exact nature of the interaction is described in this review article. It describes how stress leads to a depletion of NAD+ and sirtuins, and causes accelerated aging. On the other hand, calorie restriction and exercise lead to increased production of NAD+, activation of sirtuins and longevity.

Details about low NAD+ activity

It is important to realize that when NAD+ is below a critical level the following disease states can develop. First, in the brain it is Alzheimer’s disease and neurodegenerative disease. Second, in the eyes macular degeneration and keratoconjunctivitis sicca can develop. Third, severe plaque-type psoriasis can occur in the skin. Fourth, the pancreas develops hyperinsulinemia and metabolic syndrome. Fifth, type 2 diabetes can make your muscles weak. Sixth, sarcopenia with loss of muscle mass and cardiovascular disease in the heart can also develop. Seventh, the liver reacts to the metabolic syndrome by causing hepatic steatosis. Metabolic syndrome causes inflammatory cytokines in the fatty tissue. Eighth, the lungs react by developing chronic obstructive pulmonary disease. Ninth, your blood can get endotoxin-induced inflammation and sepsis from bacteria. A lack of NAD+ causes all of these negative changes simultaneously in the body.

In fact, when a person exercises regularly, uses intermittent fasting as a tool of calorie restriction and takes supplements of NAD+ all of these negative processes stop and sirtuins are activated restoring the body to a more youthful condition.

Summary about the effects of NAD+

In other words, NAD+ is important for cardiometabolic health, energy balance, liver health, immune health and cognitive health. NAD+ is also involved in maintaining the membrane polarity of cell walls. The blood /brain barrier and the gut/blood barrier are also kept intact by NAD+. In addition, NAD+ is involved in detoxification and control of the action of free radicals. It also is important to control Inflammation. For these reasons, it is not a surprise that people with normal NAD+ function will be healthier than those who have a problem with this.

Sugar reduces NAD+ to NADH

It is important to note that scientists could show in animal models and in humans that sugar overconsumption leads to the reduction of NAD+ to NADH. All of the negative effects described above for low NAD+ are then coming true. NADH is a reduced and disabled form of the oxidized NAD+. In essence, this substance has no biological action.

Energy metabolism

Biochemists have determined with regard to the energy metabolism of mitochondria that there are three occasions where enzymes are dependent on NAD+. Without NAD+ the energy-providing oxidative metabolism in mitochondria would not take place. As NAD+ is lower in older age, this explains why an aging population has less energy. In addition, as we age, the number of mitochondria per cell is decreasing. That is to say that an aging population has less energy than youthful people.

Other factors that are important in preserving youthful power

The AMPK signalling pathway

AMPK stands for 5′ AMP-activated protein kinase. This is an enzyme that consists of three protein portions. In humans it is expressed in liver, brain and muscle tissue. It provides energy in the liver by fatty acid oxidation. In muscles it stimulates glucose uptake and fatty acid oxidation. AMPK also inhibits cholesterol synthesis, lipogenesis and triglyceride synthesis. Fasting and exercise can stimulate AMPK production, which in turn will stimulate SIR1 genes and NAD+ production. This is especially happening in muscle tissue. To put it another way, there are a close-linked metabolic reactions between NAD+, AMPK and sirtuins.

Balance between AMPK, NAD+ and methylation

Given the right circumstances this can lead to detoxification, longevity and energy. This is what intermittent fasting and exercise can do for you. AMPK needs high NAD+ levels to give you all of the benefits. But NAD+ must be balanced with methylation. This is a somewhat difficult subject to explain, but the link explains it in somewhat technical terms. In other words, with a balance of the body’s biochemistry the person is healthy. When there is a disbalance, you get sick.

Practical application how to supplement for preserving youthful power

Dr. Shade asked the rhetorical question: how can we achieve a balance between NAD+ and methylation?

His answer is to supplement with the following supplements.

  • Trimethylglycine (Betaine) 2‐5g/day
  • Vitamin B2: 10‐30mg/day
  • SAMe or methylcobalamin 1000‐3000mcg/day
  • Measure Homocysteine as marker of methylation; if it is low, the methylation pathway is normal and there is balance.

Next: how to we raise NAD+? The answer is by cardio-metabolic blending.

  • Berberine and quercetin (they are respiratory chain modulators)
  • Resveratrol, silymarin and lipoic acid (they are liver kinase B1 activators)
  • Resveratrol or pterostilbene and quercetin (they are sirtuin activators)
  • Nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) 200- 400 mg per day
  • Trimethylglycine (Betaine) 2-5 grams per day and methylcobalamin, B2, and others (methylation support)
Preserving Youthful Power

Preserving Youthful Power

Conclusion

It is difficult to describe energy flow in biochemical terms. Dr. Christopher W. Shade did exactly that in a lecture he gave at the 27th Annual World Congress on Anti-Aging Medicine in Las Vegas on Dec.13, 2019. The key for preserving youthful power is to balance the metabolism that occurs in the nucleus of the body cells with the metabolism taking place in the mitochondria. The mitochondria are the energy producers, but the steering of this occurs through the metabolic products from the cell nucleus. NAD+ plays a key role in our energy metabolism. But there is an interplay with AMPK, which stands for 5′ AMP-activated protein kinase. Sirtuin genes interact with these messenger molecules as well and this is where longevity comes in.

Longevity through sirtuin stimulation

Sirtuins are longevity genes that help us get more energy for a longer period of time. Regular exercise stimulates this complex biochemistry giving us extra NAD+ for energy. Intermittent fasting also stimulates sirtuins, which adds to the extra energy and gives us longevity. This is not a bad deal when you look at it from a distance. We can achieve a lot preserving our energy through an active life style. Supplements can be an auxiliary measure, but they are not effective enough without positive lifestyle choices.

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Aug
10
2019

Fasting Mimicking Diet For 5 Days Every Month

In December 2017 I heard Dr. Longo speak at a medical conference in Las Vegas. He suggested the use of the fasting mimicking diet for 5 days every month. I am getting into the age group where a little help from nature would not harm (I am 74 years old). I started immediately in December 2017 to do a fasting mimicking diet (FMD) for 5 days.

Effects of fasting mimicking diet

In the beginning you just notice that you are not as hungry as you thought you would be, because you do take in three mini meals of about 200 calories each, which curbs your appetite. It is also important to consume enough liquids. Please note: liquids! Not liquor! Wine, beer or any alcoholic drinks are not part of the diet. You can drink water, but, this may get boring, and you can take water with lemon, herbal teas, black tea and coffee, as long as you stay away from sugar-laced drinks.

How the FMD works

Your total calorie intake will amount to no more than 600 calories per day for the 5 days where you do the fasting mimicking diet. Your body mass index (BMI) decreases between 0.1 and 0.4 per day to a total of 0.5 to 0.9 for the 5 days. This does not seem much, but if it is accumulating every month, a person who is obese now could have a normal weight within one year. The first day of this fast may present some challenges. I found that in the afternoon I felt hungry. What helped was a hot drink( tea, coffee, clear broth). Day two was better, and from day three it has become a routine. There are  no ferocious hunger pangs, no headaches or feelings of weakness or tiredness. I am always surprised that my energy level is improving when I do the fasting mimicking diet for 5 days every month.Dr. Longo suggests not to exercise during the fast. It is obvious that this time is not suitable for half- marathons or taxing hikes, but I found that thirty minutes of aerobics and thirty minutes of weight training felt good. Listen to your body! If you feel lightheaded at any time, stop! The emphasis is on “moderate”.

Dr. Longo noticed the following findings in a mouse model as well as on humans. I summarized this before in a previous blog:

Specific results when on the fasting mimicking diet for 5 days every month

  • Obesity diminishes, because of the weight loss effect due to missing calories.
  • Diabetes: insulin resistance becomes lower and blood sugar levels drop.
  • High blood pressure reduced: many patients were able to reduce their medications or discontinue them
  • Pain conditions improve as all kinds of pain disappears, an effect for which there is no explanation at this point
  • Autoimmune diseases like MS and rheumatoid arthritis improve, likely because of the effect of increased stem cell circulation
  • Prevention of heart attacks and strokes because of reduction of LDL, triglycerides and CRP
  • Cancer cure rates improve by protecting normal cells, the bone marrow and stimulating the immune cells
  • Longevity improved in mice with a 3-fold increase of their life span. Telomere length in humans was increased. Increased stem cells will find defective areas that need repair. This effect leads to less disease in older age.

Meal samples of fasting mimicking diet

Dr. Longo developed a kit containing all pre-packaged foods for 5 days under the name “ProLon Fasting Mimicking Diet”. The package is not larger than a shoebox, and the diet is plant-based, has some nutrition bars, drinks as well as freeze-dried soups. You can argue about the nutritional value, as it has an average rating of 3.5 out of 5. It also comes in at a hefty price of 300.00 USD. In reality it is a matter of calorie-math to consume very little food. There are plenty of tables available on the Internet that tell you the nutritional value of foods, and it does not take much effort to compose your own menu.

Here is a fairly typical list of foods

Breakfast: A typical breakfast consists of 2 slices of rye crisp bread (Wasa or Ryvita) with a bit of almond butter on it, a cup of coffee and either black or with stevia and milk.

Lunch: 8 oz. of tomato soup and coffee or tea.

Dinner: A tossed salad with organic bell peppers, ½ tomato, and two thin slices of avocado, vinegar and 1 tablespoon of olive oil.

Here is an alternative meal sample:

Breakfast: Eat a nutrition bar that is based on nuts. It should not be more than 250 calories. Alternatively make your own! Have tea or coffee.

Lunch: 8 oz. of homemade vegetable soup without the addition of pasta or beans.

Dinner: Miso soup and 4 rice crackers, alternatively a small tossed salad with olive oil and vinegar.

Results of fasting mimicking diet for 5 days every month

Here are typical results that I found over several months. I am using body composition scales every day to measure my weight, body fat percentage, visceral fat percentage, muscle percentage, calories burnt and the BMI.

One month the BMI went from 21.9 to 21.1 during a 5-day FMD. Another month the BMI experienced a reduction from 21.7 to 21. 2. Here is a list of the some of the 5-day losses of my BMI on a couple of occasions: 0.8, 0.4, 0.9, 0.7, 0.6, 0.5, 0.7 and so on.

It is important that you are not going on an eating binge after those five days. The FMD conditioned your body to be content with very small amounts of food. Enjoy your food, but stick to moderate portions.

Discussion of fasting mimicking diet for 5 days every month

An intermittent fasting mimicking diet was shown to have a diversified positive health effect in both animal models and humans. For instance, inflammatory bowel disease improves on FMD by improving the bowel microbiota and by promoting the intestinal regeneration.

Intermittent fasting, as this article shows, can prevent age-associated diseases.

This article suggests that T-killer cells that attack cancers are promoted by the intermittent fasting mimicking diet.

A FMD in type 1 diabetic patients has been shown to restore insulin generation in islets of the pancreas of these patients. The result was an improvement of their type 1 diabetes.

More research data on fasting mimicking diet

A clinical trial with 100 subjects was undertaken by Dr. Longo and his research team. He measured markers after 3 cycles of a fasting mimicking diet for 5 days every month. They found that the FMD reduced aging markers, improved diabetes and reduced susceptibility for cancer and cardiovascular disease. In another publication Dr. Longo and co-authors describe how autoimmune diseases can be improved by the use the fasting mimicking diet for 5 days every month.

Another publication by Dr. Longo describes that “age-related disorders including diabetes, cardiovascular disease, cancers and neurological disorders such as Alzheimer’s disease, Parkinson’s disease and stroke” can be prevented by fasting mimicking diet for 5 days every month.

Even cancer prevention and cancer treatment can be helped by the fasting mimicking diet.  The FMD makes chemotherapy more tolerable.

Fasting Mimicking Diet For 5 Days Every Month

Fasting Mimicking Diet For 5 Days Every Month

Conclusion

I have shown that with the fasting mimicking diet (FMD) done for 5 days in every month you can lower your body mass index (BMI) by 0.4 to 0.9 units. On the long-term this helps you to keep your BMI stable and in the 21.0 to 22.0 range. Dr. Longo has researched the effect of the FMD in both mice and humans. He found that you age better with less age-related diseases. In addition, inflammatory bowel disease, autoimmune diseases like MS, rheumatoid arthritis and type-1 diabetes improve. Cancer patients who need chemotherapy tolerate it better. Their immune system also produces more killer T cells that destroy cancer cells. The FMD prevents heart attacks, strokes and cancer. Dr. Longo also has shown that there is stimulation of stem cell production and telomeres are increasing in length. Telomeres are important for longevity, which allows you to age healthier with less disease.

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