May
23
2022

What Works for Permanent Weight Control

A recent publication examined what works for permanent weight control and what not. The study came from the Queen’s University in Kingston, Ont., AdventHealth, Fla. and the University of Alabama, Birmingham, Ala.

320 sedentary adults who were overweight or had obesity were treated by monitoring alone or by doing “small change approaches”. Both groups were observed for 3 years. The “small change approach” consisted of increasing their activity by 2000 steps per day and by limiting their food intake by 100 kcal per day. The researchers measured the weight, waist circumference and cardiorespiratory fitness of all the subjects.

The results at 3, 6, 12 and 15 months from the start showed significant reductions in weight. However, by 24 and 36 months the subjects had regained body weight.

Results of the study

Results from both groups, the non-intervention group and the small change group, were stacked against each other. There was no significant difference in terms of weight loss between 24 and 36 months into the trial. The researchers concluded that the approach of small change interventions failed.

Another approach to permanent weight loss

Valter Longo, a professor at UCLA, California has established that the fasting mimicking diet can help people to lose the last pounds that are difficult to lose. Patients do a 5 day semi-fast for 5 consecutive days, once per month. They eat three meals per day, but the total daily calorie consumption is only 500 to 800 calories. The calorie deficit leads to a reduction in body mass index between 0.3 and 0.9 for every monthly fasting mimicking diet. I have followed Dr. Longo’s fasting mimicking diet since December 2017. This allows me to keep my body mass index between 21.0 and 22.0.

Conditions that respond to the FMD

The following list shows some of the conditions that respond favorably to the FMD.

  • Obesity, because of the weight loss effect
  • 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
  • Prevention of heart attacks and strokes
  • 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 because of reduction of LDL, triglycerides and CRP
  • Cancer cure rates improved by protecting normal cells and bone marrow function
  • 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 opens up a new chapter in medicine.

The above was previously published here.

Discussion

The 3-year study that I mentioned at the beginning of this article showed that for the group that made “small changes” for 2 years there was a slight weight loss with a reduction of 100 calories per day. However, the patients got tired of dieting and regained their lost weight between 2 and 3 years. In contrast, the fasting mimicking diet requires a 1200 to 1500 calorie reduction for 5 days of each month. After a few months the patient becomes highly aware what leads to weight gain and what not. I use electronic body composition scales daily where I can determine weight, fat percentage and muscle percentage. It also records calories consumed and the body mass index (BMI).

Watching your fat percentage and BMI

I record all this data in a little booklet. Once per month I see that the fasting mimicking diet lowers my body mass index by 0.3 to 0.9 points. There is the negative experience of eating ice cream or a New York cheesecake that within one day shows as an increase in fat and the BMI. On the other hand, it is encouraging to see your elevated BMI melt away in only a few days every month. This motivates you over the years to cut out the big diet offenders and to keep your eating portions smaller. Also, you value the neutral effect of berries and vegetables.

What Works for Permanent Weight Control

What Works for Permanent Weight Control

Conclusion

An interesting diet study of 3-year duration showed that small caloric reductions of 100 calories per day are ineffective over a longer period of time. In this study the effect of small caloric reductions wore off after two to three years. On the other hand, I experienced the effects of the fasting mimicking diet (FMD) of Dr. Longo for more than 4 years. This helps me to keep my body mass index (BMI) in the 21.0 to 22.0 range. Without the FMD I would slowly slip into the overweight category. Following the FMD every month and recording the body composition scale values daily keeps me motivated to watch what I eat resulting in persistently low BMI values. Knowing that this is also a key to health keeps should keep anybody motivated.

Mar
30
2022

Adolescents’ Lifestyles Are Linked to Faster Aging in Adulthood

A longitudinal study found that adolescents’ lifestyles are linked to faster aging in adulthood. The study started with a baseline examination in a group of adolescents around the age of 15. 30 years later doctors examined the same individuals again. The researchers found that smokers, obese people and people with untreated emotional problems were aging faster than controls who did not have these problems. CNN discussed this study as well. A fourth condition, asthma was also included in the study. Indeed, adolescents who suffered from asthma in their mid-teens were not more biologically aged at age 45 when compared to controls who never had asthma. The authors concluded that treated asthma did not prematurely age a person. However, lifestyle habits like smoking, excessive weight and untreated mental illness contributed to accelerated aging.

Does having a healthy lifestyle lower your risk of developing medical conditions and diseases?

It must be remembered that anti-aging medicine is watching out for new treatments that can prolong life. However, this is not just one “breakthrough”, but rather a number of factors that in combination lead to longevity.

Resveratrol

Resveratrol, the supplement from red grape skin can stimulate your mitochondria metabolism. Exercise more and regularly as this will also stimulate your mitochondria to multiply similar to the effects of PQQ, a supplement. I take 500 mg of resveratrol concentrate once daily.

Exercise regularly

The first thing to remember is that regular exercise will prevent about 50% of chronic diseases (diabetes, heart failure, arthritis). Consequently, this prolongs life: Lack of exercise is a major cause of chronic diseases.

Replacing missing hormones with bioidentical hormones

When you enter menopause or andropause replace missing hormones with bioidentical hormones. This will add 10–15 years of good life. This information comes from the anti-aging medicine circles and European studies of women on bioidentical hormone replacement. Here is a more conservative opinion from a US review: Counseling Postmenopausal Women about Bioidentical Hormones: Ten Discussion Points for Practicing Physicians.

Abandon sugar, starchy foods

Starchy foods (potatoes, pasta, rice, pastries and bread) and processed food accelerate aging. Avoid these foods for a healthier heart – Harvard Health. Many studies have confirmed that a Mediterranean diet is anti-inflammatory and prevents premature aging.

Are you deficient in human growth hormone?

Find out whether you are deficient in human growth hormone or not by taking an IGF-1 blood test. Dr. Hertoghe, an endocrinologist from Belgium said at various anti-aging conferences that HGH by itself prolongs life by about 15 to 20 years or more. I am deficient in HGH and I am injecting HGH myself regularly. My anti-aging physician orders my IGF-1 level three to four times per year to monitor the right dosage of HGH replacement. But it is crucial that the physician supervise the patient. This involves  giving the patient only minimal amounts of HGH, which keeps IGF-1 levels in the high normal range. This is also re-emphasized in this review: Growth Hormone and Aging: Updated Review. When you overdose HGH, you lose all of the beneficial effects that HGH replacement brings.

Fasting mimicking diet (FMD)

Fasting for Longevity: 9 Questions for Dr. Valter D. Longo. When you consume only 500 to 600 calories daily for 5 days out of every month you are stimulating your telomeres (the caps on your chromosomes) to grow a little bit longer. Longer telomeres translate into longer life expectancy. In addition, your stem cells anywhere in your body also undergo stimulation. Here is more information: fasting mimicking diet for 5 days every month.

Lifestyle factors

It is best not to smoke. Keep your body mass index in the 21.0 to 22.0 range. Get enough sleep (7–8 hours every night). Use a form of relaxing exercise (yoga, self-hypnosis, meditation, Tai-Chi). This will keep the stress hormone cortisol under control; if it is constantly high from ongoing stress, it leads to premature deaths. The Science of STRESS – SLMA

Take key vitamins and minerals

When you take key vitamins and minerals every day you can add another 5 to 10 years of disease-free life to your life expectancy. Ray Schilling’s answer to Is taking vitamin supplements helpful or quackery?

All of these factors taken together help you to not age prematurely. A healthy lifestyle elongates your telomeres, which prolongs your life without diseases. It also prevents heart attacks and strokes, which again prolongs your life. And a healthy lifestyle prevents Alzheimer’s disease, so you can turn old and not have to worry about memory loss. I cannot overemphasize how important a healthy lifestyle is!

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Conclusion 

As summarized above, a recent study going on for about 30 years showed that premature biological aging occurs in adolescents who smoked, were obese or had untreated mental illness. On the other hand, treated asthmatics did not show this biological aging effect. I summarized what factors contribute to slowing down aging. It is a combination of proper diet, regular exercise, hormone replacement as you age and taking some supplements. One key to slower aging is to be aware of how important a healthy lifestyle is for you.

The section about having a healthy lifestyle was published previously here: Ray Schilling’s answer to What are the most exciting breakthroughs in longevity research?

Feb
13
2022

How healthy are Carbohydrates?

A recent review article asked: how healthy are carbohydrates? The three food components that occur in natural food are carbohydrates, fats and protein. Among the carbohydrates it is important to distinguish between simple carbohydrates (such as sugar) and complex carbohydrates. Simple carbohydrates are readily absorbed into the blood, which causes an insulin peak. After a few hours the peak is gone, and there is a “crash”. You will know the feeling of feeling hungry just a few hours after eating doughnuts! Complex carbs like peas, beans, fruit and vegetables take longer to get digested. The final breakdown product of the digestive process is sugar as well. But this process takes longer meaning that the concentration of sugar in the blood is much lower. There is also no “crash”. The result is that complex carbs cause less insulin secretion into the blood.

Long-term effect of eating too much sugar

Integrated over several decades of life, this means that a person who constantly consumes beverages with sugar and snacks containing sugar is at a higher risk of developing type 2 diabetes. In contrast, a person who eats well balanced meals where the insulin secretion is low, will not develop diabetes and have much less hardening of the arteries. This translates into a lower risk to develop heart attacks and strokes.

The types of carbohydrates

Before I discuss the health effects of various carbohydrates, we need to look at the types of carbohydrates.

Simple carbohydrates

Table sugar is a disaccharide, which consists of one molecule of glucose and one molecule of fructose.

The enzyme amylase very quickly breaks down the chemical bond between fructose and glucose and creates these monosaccharides in the small intestine from which they are rapidly absorbed. Milk sugar is a disaccharide, which consists of a molecule of glucose bound to a molecule of galactose. Milk contains 2 to 8% of milk sugar. We have to watch these simple carbs, because they trigger insulin production and lead to accelerated hardening of the arteries, heart attacks and strokes.

Complex carbohydrates

In contrast, complex carbs are healthy, because they take some time to be digested in the digestive tract. They consist of polysaccharides, long chains of sugar molecules. Both starches and dietary fiber consist of complex carbohydrates. They often are present in vegetables and many fruit. Complex carbs slow down the absorption of their breakdown products and minimize the insulin response. Dietary fiber is the indigestible part of fruit and vegetables. It contributes to good gut health as the beneficial gut bacteria can multiply on the fibre particles.

Healthy carbs

When simple carbohydrates dominate in our food intake, we are in trouble because they are loaded with calories. Overconsumption of them leads to weight gain and obesity, to diabetes, heart attacks, strokes and even cancer. On the other hand, consumption of complex carbohydrates is healthy. We get them from eating apples, bananas, berries, vegetables like spinach, tomatoes and carrots. Other healthy complex carbs are whole grain flour, quinoa and brown rice. Black beans, lentils, peas and garbanzo beans are also healthy complex carbs. Dairy products like low fat milk, yogurt and ricotta cheese are healthy as well.

Mediterranean diet as an example of a healthy, balanced diet

In 2019 a study was published where women with polycystic ovary syndrome (PCOS) were either put on a Mediterranean diet or not. This study showed that a Mediterranean diet was anti-inflammatory, reduced insulin resistance and reduced testosterone levels in PCOS patients.  But the same is true in a general population. The Mediterranean diet is one example of a healthy, balanced diet with complex carbohydrates. It prevents insulin resistance, inflammation and hormone disbalance. Other diets have similar effects like the DASH diet, the Zone diet and the Pritikin diet.

Quantity and quality of your food intake matters

A 2018 study from India showed that it matters how many carbohydrates we consume.  On average Indians eat a diet with 65-75 percent of calories coming from carbohydrates. Many of these carbs are the unhealthy simple carbohydrates. How healthy are  carbohydrates? The authors recommended to reduce complex carbohydrates to 50-55% and to add 20-25% protein, mostly from vegetable sources and add 20-30% from fat. The fat consumption needs to include monounsaturated fats (e.g., olive oil, nuts and seeds). Among the carbs a lot of green leafy vegetables help to balance the diet. This prevents the development of type 2 diabetes, heart attacks and strokes.

The above addresses the issue of quality of food. But it is also important what quantity of food we are eating. This is where counting or estimating calories comes in. If we overeat, we will very quickly gain weight and eventually can develop obesity.

The glycemic index and glycemic load

In order to help you with the choice of right carbohydrates the glycemic index was developed.

Here is another reference about the glycemic index/glycemic load.

In table 1 towards the end of the last link you find a column designated “GI” for glycemic index. All the foods that have a value less than 55 are foods that you can eat freely.

Problematical carbohydrate foods

Baked russet potatoes and boiled potatoes are very high on the GI index list. Puffed rice cakes, doughnuts, jelly beans and corn flakes measure high on the glycemic index list. But water melons, dried dates, white bread and white rice are also items to be avoided.

You best avoid anything with a glycemic index above 55. The column to the right of GI shows you a serving size and the last column on the right the glycemic load. The lower the glycemic load per serving, the better it is for your health. The glycemic index and the glycemic load are useful concepts of helping you to sort out your diet items.

My wife and I used this in 2001 to shed weight. We both lost 50 pounds (=22.72 kilograms) each in a period of 3 months.

Fasting mimicking diet (FMD)

According to Dr. Longo intermittent fasting stimulates the stem cells of the bone marrow. This leads to new clones of lymphocytes (B cells and T cells), which are part of the immune system. Your immune system becomes stronger from this.

Dr. Longo has done detailed mouse experiments, which inspired him to develop a new diet plan. Patients would receive a fasting mimicking diet (FMD) on 5 consecutive days per month. The rest of the month consists of a normal, balanced diet. 5 days of the month the person consumes a low 600-800-calorie diet. This reduced calorie intake is enough to ensure adherence to the diet, but low enough to lead to enormous positive metabolic changes including youth-preserving stem cell stimulation.

I am following the FMD

I have followed a FMD since December 2017. It helps me to keep my weight (BMI) in the 21 to 22 range. I feel more energetic and have managed to stay in good health.

The above chapter on the FMD was previously published here.

How healthy are Carbohydrates?

How healthy are Carbohydrates?

Conclusion

Healthy eating consists of 50-55% calories from complex carbohydrates; add to this 20-25% protein, mostly from vegetable sources and add 20-30% of total calories from fat. The fat consumption needs to include monounsaturated fats (e.g., olive oil, nuts and seeds). Unfortunately, most “convenience foods” (=processed foods) are incompatible with a healthy lifestyle. They contain too much simple carbs (sugar). Many people live on 65-75 percent of calories coming from simple carbohydrates, which are too many carbs. It should be complex carbs that digest slower and that do not induce insulin resistance. The glycemic index and glycemic load are useful concepts to help you chose the right foods that keep you healthy. The fasting mimicking diet can help you to take the last few pounds off that may be difficult to shed. Weight loss and weight maintenance are possible when you choose the right foods.

Nov
21
2020

Antibody Treatment for Rheumatoid Arthritis Was Superior

Researchers found that antibody treatment for rheumatoid arthritis was superior to conventional therapy. In particular, rheumatoid arthritis is an autoimmune disease where autoantibodies attack the synovial lining of joints. In this case, subsequently macrophages are activated, which attack joint surfaces. As an illustration, this process leads to crippling joint deformities.

The original study was published in June, 2019, but this is difficult to understand. The magazine Sciworthy published a review article on August 24, 2020 with more understandable language.

To emphasize, in mouse experiments the researchers found that only a small subfraction of activated macrophages caused symptoms of rheumatoid arthritis. They were folate receptor beta (FR-β) positive macrophages. It is important to realize that the researchers found them both in mice with rheumatoid arthritis and in man. The evidence in humans were the same findings in human tissue samples of people with autoimmune diseases.

Details of mouse experiments

Folate receptor beta (FR-β) positive macrophages are key in mouse model of RA

Explicitly, the researchers started experiments with a mouse model of rheumatoid arthritis, because it is easier to do than human research. They found that the key to developing rheumatoid arthritis was the presence of folate receptor beta (FR-β) positive macrophages. Chiefly, macrophages remove cell debris, bacteria or viruses from the blood. However, once they are activated and they carry FR-β receptors on their surface, they destroy joints. Certainly, in the mouse model monoclonal F3 antibodies were developed that kill activated macrophages. On the contrary, the human equivalent for the F3 antibodies is monoclonal antibodies with the name m909. They are directed at the FR-β receptors on the surface of activated macrophages. But first to the mouse experiments.

Inflammation from intraperitoneal injection of thioglycollate

In the first place, the researchers created an inflammatory condition by injecting thioglycollate into their peritoneal cavity. They could demonstrate that inflammation did occur. With this in mind they found macrophages in the peritoneal fluid. There were a lot of activated macrophages in it. Histological slides were analyzed with the help of F3 antibodies. In this case they visualized the activated macrophages. Subsequently the researchers treated mice with varying concentrations of monoclonal F3 antibodies. They found that the higher concentrations cured intraabdominal inflammation of the mice.

Researchers used monoclonal F3 antibodies to treat mouse model of RA

The researchers treated collagen-induced arthritis next in a number of experiments. Several concentrations of monoclonal F3 antibodies were given to these mice. Other experiments showed that monoclonal F3 antibodies specifically attacked only the activated macrophages and killed them. The killing of the activated macrophages in the mouse model of rheumatoid arthritis cured the arthritis. Fig. 5 shows this.

Mice treated with maximum concentrations of monoclonal F3 antibodies showed decrease in bone density

Next the researchers treated rheumatoid arthritis mice with maximum concentrations of monoclonal F3 antibodies to treat the arthritis. The swelling of their paws went down completely. CT scans of the bone in the paws showed decrease in bone density, while untreated controls showed significant loss of bone density. Monoclonal F3 antibodies were indeed a cure for RA in mice (Fig. 6).

Human experiments

Researchers confined human experiments to tissue samples from patients with various autoimmune diseases. Skin biopsies from patients with psoriasis, scleroderma, and sarcoidosis showed the distribution of FR-β-positive macrophages by special staining. This staining technique used human monoclonal antibodies (m909) against human FR-β receptors on activated macrophages. The publication depicts images that show abundant activity in all three autoimmune diseases (Fig. 1).

Researchers examined tissue samples from other autoimmune diseases with monoclonal antibodies (m909) against human FR-β receptors. The activated macrophages including rheumatoid arthritis, Crohn’s disease, ulcerative colitis and idiopathic pulmonary fibrosis lit up on fluorescence microscopy. In addition, nonspecific interstitial pneumonia, chronic obstructive pulmonary disease, systemic lupus erythematosus, psoriasis, and scleroderma tested positive as well.

Future therapy possibilities of rheumatoid arthritis with monoclonal antibodies

A series of experiments showed that two mechanisms can eliminate FR-β-positive macrophages: complement-dependent cytotoxicity and antibody-dependent cell cytotoxicity. It means that there is a strong possibility that autoimmune diseases may be treatable with monoclonal antibodies. Fig. 2 summarizes these experiments.

Conventional therapy for rheumatoid arthritis

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 sulfasalazine 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. Research described here proved that antibody treatment for rheumatoid arthritis was superior to conventional therapy in a mouse model.

Discussion

Monoclonal antibodies (m909) against human FR-β receptors targeting activated macrophages opened up a new therapy method against rheumatoid arthritis. The equivalent F3 antibodies in mice were a useful tool to expedite research in this field. The publication that I reviewed here was able to combine mouse experiments and work on human tissue samples essentially showing the same results . Monoclonal antibodies (m909) against human FR-β receptors work potentially like a broad-spectrum anti-inflammatory drug. The monoclonal antibodies reduce the accumulation of inflammatory immune cells, which treats the cause of rheumatoid arthritis. This will likely be the future cure of rheumatoid arthritis and other autoimmune diseases. We urgently need clinical trials to prove in humans that the findings from a mouse model and human tissue samples are correct.

Antibody Treatment for Rheumatoid Arthritis Was Superior

Antibody Treatment for Rheumatoid Arthritis Was Superior

Conclusion

Researchers recently showed in a mouse model that a small portion of activated macrophages cause rheumatoid arthritis (RA). But they also examined many biopsies from patients with autoimmune diseases. The findings in human tissue samples were identical to the findings in a mouse model. Activated macrophages are sensitised to attack the linings of joints as is the case with rheumatoid arthritis. These macrophages develop special receptors, called folate receptor beta (FR-β), and the macrophages release cytokinins. The cytokinins (TNFα, IL-1, IL-6, IL-12 and others) cause inflammation and make the RA worse. They also recruit more neutral macrophages and convert them into activated macrophages. The research group found that monoclonal antibodies against human or mouse FR-β receptors killed the activated macrophages. This alleviated the arthritic symptoms and after enough antibody treatments cured the RA. There were no negative effects on the rest of the immune system.

Physicians will cure human autoimmune diseases with monoclonal antibodies in the future

Researchers demonstrated this mostly in a mouse model. But the authors have manufactured human monoclonal antibodies against the FR-β receptors of activated macrophages. This has set the stage for curing human autoimmune diseases with monoclonal antibodies as well. At this point there is a need for clinical trials with various autoimmune diseases including rheumatoid arthritis with monoclonal antibodies against activated macrophages.

Oct
17
2020

What can Happen to Your Body Over Months of Isolation

A recent article by CNN describes what can happen to your body over months of isolation at home. The article is rather negative showing all the possible things that can go wrong. I have been isolated as well since March 2020. I handle the isolation differently than described in the article. I will comment to each point what can be done differently to avoid the complications mentioned.

Muscle loss

The CNN article makes the point that inactivity can make you lose muscle bulk within only one week. A lack of exercise weakens your muscle strength. And muscle strength has been associated with longevity.

My comment:

I do a brisk walk of 5 to 7 kilometers daily. This maintains my muscle bulk. But I have a treadmill in the basement and a couple of weights that I can use, if it rains outside.

There is a danger that heart and lungs get weaker

You need to raise your heart rate and you also need to perfuse your lungs through exercise. Many people do not like exercise. They sit in front of the TV for hours or they surf the net on the computer. Even just reading a book does not give you enough exercise to get your heart rate up and increase your lung perfusion.

My comment:

A brisk walk with proper distancing gives you fresh air, exercises your muscles, your heart and your lungs. It maintains your cardiovascular fitness.

Weight gain

Being home all the time allows you to look into the fridge more often and eat snacks that are processed. People tend to eat more often than 3 times a day. The end result is that you gain weight. In the beginning of the epidemic people stocked up on non-perishable foods. Often they contain more sugar and carbohydrates. Consuming these foods leads to weight gain. Wearing masks, frequent hand washing, isolation practices and change of normal routines makes people get stressed. Stress leads to overeating and weight gain.

My comment:

In the last 6 months that I did home isolation my body mass index (BMI) stayed in the 21.0 to 22.0 range. I ate three meals a day. I avoided processed foods as they are overloaded with sugar, salt and refined carbs. Once a month I do a 5-day fasting mimicking diet according to Dr. Longo. This ensures that my BMI stays within the range I indicated. Otherwise I eat a Mediterranean diet, which is anti-inflammatory.

Your posture could suffer

When you are seated in front of the computer or the TV you tend to engage in poor postures. This can lead to strains of your back, neck, shoulders and hips. Staring at the computer screen or the TV can also give you eye strain.

My comment:

The key is movement, such as getting up and walking around; doing other activities like lawn mowing, weed eating or doing dishes. This interrupts any longer stretch of bad posture.

Your sleep quality can suffer

The more exposure to sunlight during the day you get, the more vitamin D you produce in the skin. Some people lack the necessary enzymes in the skin to convert cholesterol into vitamin D. But exposure to sunlight also helps to reinforce your diurnal hormone rhythm. This is also called circadian rhythm. Avoid blue lights (TV, computer, iPhones etc.) in the evening before bedtime as this can interfere with a deep sleep later. Also go to bed early enough (between 10 and 11 PM) to allow your circadian rhythm to take over.

My comment:

Some people (above the age of 60) benefit from 3 mg of melatonin at bedtime. After the age of 60 people no longer produce enough melatonin in the pineal gland. If I wake up in the middle of the night, I take another 3 mg of melatonin prior to 3AM. Caution: after 3 AM melatonin can give you a bit of a hangover in the morning.

Your brain can slow down

The brain needs nutrition and exercise. Exercise can eliminate certain amino acid by-products that otherwise turn into neurotoxins. With exercise you even prevent neurotoxins to enter the brain.

My comment:

I find that I must at least do a brisk walk of 4 kilometers a day. It prevents back pain, helps me sleep better and keeps my mind clear. But as mentioned earlier I prefer doing a brisk walk for 5 to 7 kilometers a day. In the past (prior to March 2020 when the Covid-19 pandemic started) I went to the gym every day. When it finally reopened, they had one Covid-19 case at the gym. I decided that it is too dangerous to go back to the gym until a safe Covid-19 vaccine is available in the summer of 2021. I feel the same way about flying. It is not worth the risk. I can just stay local and do my own program. The pleasure of traveling can wait until the summer of next year.

What can Happen to Your Body Over Months of Isolation

What can Happen to Your Body Over Months of Isolation

Conclusion

A recent CNN article described the dangers of passively staying in home isolation. I felt that this article was on the negative side. I found that by including a regular brisk walking program into my daily lifestyle the day got more structured. I felt I had more energy and I had no aches or pains. If I spent too much time watching TV or spending in front of the computer, I developed back aches and felt sluggish. I incorporated a 5-day fasting mimicking diet according to Dr. Longo once per month into my regular Mediterranean diet. This allowed me to keep my body mass index in the 21.0- 22.0 range. Doing what I described above I could continue to hold my weight, have energy and stay pain free for many more months. But when the Covid-19 vaccine arrives in spring/summer of 2021 I hope that things will return to normal.

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.

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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  are products of mesenchymal stem cells can 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 of 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.

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.

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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