In an increasingly aging society, health in old age plays an increasingly important role. For each individual, but also for society and the healthcare system. It is not primarily about simply extending the maximum lifespan (“Lifespan”) or even about “immortality”, but rather about the unfortunately often long illness at the end of life to avoid or at least significantly shorten it and to extend as much as possible the period of life that we can enjoy in the best health (“Healthspan”).

 

Why are people getting older today than before?

In humans, external factors such as better hygiene, nutrition and medical care have led to a significant increase in average life expectancy in industrialized nations:

Residents of Germany who are 100 years old and older (Source: Stat. BA, Human Mortality Database, Robert Bosch Foundation):

• 1980: 975 (GDR + FRG)
• 2000: 5.699
• 2017: 14.194
• 2037 (e): ~140.000

Proportion of people over 80 in Germany:

• 1950: 0.1%
• 1975: 2.2%
• 2000: 3.6%
• 2025(e): 7.4%
• 2050(e): 13.2%

However, some aging researchers doubt whether the maximum attainable age, the so-called maximum lifespan, can be extended. Because unlike the average life expectancy, the maximum has hardly increased:

The person with the longest documented lifespan was the Frenchwoman Jeanne Calment, who was born in 1875 and died in 1997, and was exactly 122 years and 164 days old. DH Since the year they were born, there has been no one who has gotten older despite all the hygienic and medical advances. This suggests that the maximum human lifespan is around 120 years.

Why, for example, are Japanese, French and Italians on the list of oldest people, but no German?

Of particular interest to longevity researchers are the so-called “blue zones”, in which a striking number of centenarians live. Sardinia and the Japanese island of Okinawa are among them.

Studies on the causes of longevity in these zones have shown that the very old there have eaten healthily throughout their lives, especially.a only a little meat (although not vegetarian), exercised regularly but moderately - and they all had strong social ties until the end of their lives.

According to a US meta-study from 2010, people with a lot of social contacts have an around 50% lower risk of dying earlier than expected. Of course, loneliness doesn't have a direct physical impact, but it does have an indirect one - because lonely people smoke more often, are more likely to be overweight and less physically active.

Long-term stress also causes people to age more quickly because more damaging stress hormones are then released.

In addition, noticeably high spermidine levels are measured in the blood in the “Blue Zones”. Spermidine is absorbed through food (plants produce it primarily.a in stressful situations itself) and also produced in the body (v.a through the microbiome in the intestine). Spermidn stimulates autophagy, i.e.H the cellular “recycling process”. Fermented soy (Japanese natto), nuts, mushrooms, wheat germ, old/ripened cheeses, and green vegetables are particularly rich in spermidine. All part of the cuisine in the Blue Zones of Japan, Italy and France.

It therefore appears that v.a Stress and diet in Germany stand in the way of particularly high longevity.

Aging processes begin at a young age: primary and secondary aging

The so-called “primary aging” begins around the age of 25. Year of life: by ~1% p.a.a decreases cell performance or cell competencies decrease. Of course, this only affects those cells that are not renewed. Not to be renewed, for example the stem cells relevant for longevity.

Examples:

• Eyes: the elasticity of the lens decreases at the age of 15, the ability to see close up decreases at the age of 40 and cataracts are at risk in old age
• Ears: ~from the age of 20, the number of hair cells in the cochlea, which are important for the perception of sounds, decreases. Age-related hearing loss often sets in after the age of 60
• Lung: at age 20, the production of alveoli decreases; Because the elasticity of the lungs also decreases, the volume of air that can be inhaled and exhaled becomes smaller
• Reproductive organs: from the age of 25, women's fertility decreases, and men's testosterone levels decrease
• Joints: from the age of 30, the cartilage loses its elasticity and the intervertebral discs become stiffer
• Skin: from the age of 30, the skin is less able to bind moisture and loses its elasticity
• Hair: from the age of 30, the production of the dye melanin decreases and then stops completely
• Bone: between the ages of 30 and 40, bone loss begins to outweigh bone formation, so that an 80-year-old only has around 50% of the maximum bone substance
• Muscles: Muscle loss begins from the age of 40 - a 65-year-old has around 10 kg less muscle mass than a 25-year-old
• Kidneys: at age 50, the filtration performance decreases, so blood purification takes longer and is less effective
• Brain: from the age of 60, the ability to react decreases, coordination skills and memory deteriorate
• Heart: at the age of 65, the heart can show signs of old age, for example the blood vessels calcify and the heart therefore has to pump against a higher resistance
• Immune system: at 65, the susceptibility to infection increases because the number of immune cells in the blood decreases

In the sixties of life, i.dR the so-called “secondary aging” noticeable in the form of typical age-related diseases such as osteoarthritis, stroke, heart attack, dementia, etc.

The number of illnesses that require intensive care and costs will therefore increase dramatically, so that health in old age will become increasingly important from both an individual and a societal perspective. Regardless of the controversial question of whether aging is a disease, as with all health issues, it is important not to combat the symptoms of aging with medication, but rather to focus on the causes of aging

Most longevity approaches are not primarily about extending the maximum lifespan, but rather about pushing secondary aging as far back as possible. DH healthy aging is the focus.

What happens to a cell when it ages?

In order to understand what happens to a cell as it ages, we first have to understand what central cell functions there are. One also speaks here of the so-called “cell competencies” – a concept that is based on Dr. Druscher goes back:

 

1. Renewal

The number of divisions that a body cell can undergo is limited. Therefore, most of our cells need to be replaced after a certain period of time.

Around 50 million cells per second (!) are exchanged in our body. Within 7 years, almost all of the body's 30 trillion cells are replaced.

For this cell renewal, v.a our stem cells are responsible. Stem cells are the reservoir for various body cells into which the stem cells can differentiate. The problem is that our stem cells themselves are not replaced and therefore “age” as DNA damage accumulates and the repair systems cannot keep up. However, the stem cell DNA must be copied absolutely error-free during cell division. Therefore, maintaining the health of stem cells is particularly important for healthy longevity.

But at some point the stem cell reservoir is exhausted and there is no more supply. In addition, blood-forming stem cells can mutate with age and then remain in the blood as pro-inflammatory clones.

The freshwater polyp Hydra has aroused particular interest among Longevity scientists because its stem cells are permanently active, so that old cells can be replaced again and again.

The idea of ​​the stem cell researchers is therefore to decipher the mechanisms of the loss of function of stem cells in old age in order to then inhibit them with new therapies and thus extend organ preservation in old age.

The cell types that are not or only slightly renewed include:a: nerve, heart muscle and sensory cells (eye, ear). We cannot stop their aging, so longevity approaches, in addition to stem cell health, are particularly important.a need to focus on these cell types.

2. Energy production

The energy for our cells is produced in the mitochondria, the power plants of our cells. The more energy a cell requires or consumed, the more mitochondria it usually has. For example, a heart muscle cell has 5000 mitochondria!

Even when at rest, the body needs about as much kg of ATP every day as our body weight! When you exercise, ATP production increases significantly.

From the 25th However, the mitochondria already lose their performance by the age of one; d.H With the same oxygen consumption, ATP production decreases, making the mitochondria more inefficient. As we get older, mitochondrial performance decreases by around 50% (!) - which can be...a This is because important elements of the respiratory chain such as coenzyme Q10, niacin (vitamin B3) or the coenzyme NAD+ (nicotinamide adenine dinucleotide) or NADH (reduced form of NAD+) decrease with age.

Free radicals are also increasingly forming in the mitochondria as waste products, which damage genetic material, organs, connective tissue, etc. harm

Diseases of the nervous system, such as Parkinson's disease is often caused by insufficient energy production in certain nerve cells. See also https://www.hih-tuebingen.de/forschung/neurodegeneration/forschungsgruppen/mitochondriale-biologie-der-parkinson-krankheit/?tx_jedcookies_main%5Baction%5D=submit&cHash=2ee0704321cb47f67169ef63d0c1c3d3

Therefore, longevity approaches must v.a the relevant factors in the citrate cycle (upstream of the respiratory chain) and respiratory chain or Focus on the electron transport chain and try to fill the deficiency, e.g. through nutritional supplements:

• Coenzyme Q10 (as a redox system (ubiquinone/ubiquinol) central component of the mitochondrial electron transport chain)
• L-Carnitine (used by.a absorbed through food (meat) and transports fatty acids through the mitochondrial membrane; In 2002, a study by the University of Leipzig demonstrated in vivo that L-carnitine can increase the breakdown of long-chain fatty acids in healthy adults without L-carnitine deficiency)
• Vitamin B6, B9 (folic acid), B12 as important cofactors

Even if we can and should influence mitochondrial performance in this way, there are still limits for us Europeans in comparison, for example. to East Africans when it comes to the performance of our mitochondria. This is due to evolution: due to the nomadic lifestyle, East Africans had to run long distances with endurance - and those with the best mitochondria survived. Therefore, even with the best training, a European can never match the energy production of the mitochondria of Kenyans or Ethiopians; so that the latter also regularly win marathons.

But regardless of the basic evolutionary equipment, we can train our mitochondria. And good mitochondrial fitness, acquired at a young age, persists well into old age. In this context, reference is often made to Churchill, who was a competitive athlete when he was young and who continued to benefit from his well-trained mitochondria in old age despite a very unhealthy lifestyle.

 

3. Detoxification

As part of cell metabolism, cellular waste is constantly produced, such as: Errors in protein synthesis (misfolded proteins) or damaged mitochondrial parts. This waste is normally broken down through cellular cleansing processes, especiallya through the so-called Autophagy, the cellular “recycling system”. The lysosomes then dock onto these waste products and their enzymes break down this waste into its individual components and thus make it recyclable. Lysosomes are therefore also called the “stomach” of our cells.

Unfortunately, as we get older, this autophagy no longer works so well, so that molecular waste accumulates in the cells and ultimately impairs normal cell functions. Over the years, this cellular waste can then contribute to the relevant diseases of old age, such as: Diabetes, Alzheimer's or Parkinson's.

One way to activate autophagy is caloric restriction (fasting). When there is a lack of food, the body activates autophagy to release nutrients from the “protein waste”. And as a side effect of this nutrient production, misfolded proteins and defective organelles are broken down. This also fits well with the observation in numerous studies that caloric restriction in laboratory animals has extended life and counteracts aging processes.

Theories of aging

 

1. Program theories
2. a) Shortening of telomeres

The telomeres are the protective caps at the ends of the chromosomes. Each time a cell divides, they shorten by a defined number of base pairs.

The shorter the telomeres are, the worse the copies turn out - until at some point they are so short that no further cell division takes place and the cell dies.

The length of the telomeres is considered an indicator of the so-called biological age, in contrast to the chronological age.

The shortening of telomeres is increased by various factors, such as: oxidative stress or chronic inflammation. The good news: Studies suggest that telomeres can also lengthen again. There are promising studies:a for vitamin D, E, ginkgo and omega 3 fatty acids. See also https://www.wissenschaft.de/gesundheit-medizin/langsamer-altern-durch-mediterrane-ernaehrung/

1. b) Hormonal control of aging

Why do members of a species live a certain lifespan in evolution? Because preserving the species is evolutionarily the most important thing. Therefore, evolution calibrates lifespan roughly to ensure breeding and sexual maturity.

This also explains why menopause only begins in women in their mid-40s.

Therefore, the hormones that are required for reproduction also have a decisive influence on lifespan. E.g. estradiol, which is not only a sex hormone, but also ensures that the stem cells in the bone marrow are maintained and multiply without differentiating too much. Only at the “site of use” such as cartilage, skin or muscle do they differentiate into the cells that are acutely needed.

2. Damage theories

Damage theories target free radicals. Free radicals have an unbound pair of electrons and are therefore particularly aggressive because they try to steal an electron from other molecules. In doing so, they are reduced and oxidize the other molecule, which itself becomes a free radical. This sets a chain reaction in motion.

Free radicals damage tissue and the DNA of our cells and thus contribute to the aging process and the development of diseases. They are created by

• Chronic/silent inflammation
• AGE formation with high sugar consumption
• External induction (smoking, environmental toxins, stress etc)
• during ATP synthesis in the mitochondria (oxygen radicals are always formed in the respiratory chain; but their proportion increases with age and ATP production decreases)

According to this theory, longevity measures must be based on defusing free radicals. This happens through so-called antioxidants. We have our body's own enzymatic antioxidant system, but it is not always sufficient to effectively defuse all free radicals. Antioxidants must therefore be supplied from outside - either through food or in highly concentrated form through suitable dietary supplements. The particularly effective antioxidants (measured by the so-called ORAC value) include, for example: Alpha lipoic acid, vitamin C and vitamin E.

 

To what extent is our age and health as we age genetically predetermined?

1. A) Genetics

Everyone knows stories like that of Helmut Schmidt, who despite a very unhealthy lifestyle (e.g.a Chain smokers) have become very old - whereas others who live very healthily die early. Here i.dR The genes were cited as the reason.

Researchers are interested in this context:a for the question of whether there is a longevity gene – the “Methuselah gene”, so to speak. And there is actually the so-called FOX03 protein, which appears to activate the increase in the enzyme sirtuin 1, which is important for longevity. Every person has this protein - but two specific variants/expressions of FOX03 are noticeably common in people over 100 years old. This was discovered in 2009 by the “Healthy Aging” research group at Kiel University. Also with the aboveG These variants of the FOX03 gene were found in freshwater polyps whose stem cells continually renew themselves.

Since the two variants of FOX03 only occur in very few people and the genetics cannot be influenced in this regard, this finding has no practical relevance in the context of longevity approaches.

Another study, the “New England Centenarian Study”, evaluated the data from 1900 people over 90 and found that survival at very old age increases to further survival to 75 % depends on good genes. D.H Only 25% of survival depends on lifestyle factors. However, it cannot be concluded from this that our fate with regard to our life expectancy is 75% genetically predetermined, because the above.G The study expressly only refers to the further life expectancy of all those who have already reached a very old age (>= 90 years).

A study that not only includes those people who have already become very old is that of Dr. Graham Ruby, who has Ancestry data (Ancestry is the world's largest genealogy research platform) from around 54 million people and their approx. 6 billion ancestors evaluated. And then a completely different picture emerges: The heritability of lifespan seems to be only a maximum of 7%.

 

1. B) Epigenetics

While genetics deals with DNA as the basic genetic makeup, which is identical in all of our cells, epigenetics is about the activity level of our genes. The fact that our ~250 cell types function so differently, even though the DNA is identical, is due to epigenetics, which controls the switching of genes on and off.

Unlike genetics, epigenetics is strongly influenced by lifestyle and environmental factors. After birth, identical twins have almost identical epigenetic patterns, which remain similar even in old age if they have a similar lifestyle, but differ just as much if their lifestyle is very different.

How does switching on/off work exactly? About the so-called “methylation”: Methyl groups are molecules made up of one carbon and three hydrogen atoms and attach themselves to certain places in the DNA - namely only where the DNA building block group CpG (cytosine-guanine) occurs, and prevent certain gene sequences from being read there , d.H “switch genes off”.

With age, methylation decreases, which means that genes that should not have been active are active and produce proteins that are not needed or can even cause bad things, such as: . Inflammation.

Steve Horvath, German professor of human genetics and biostatistics at the University of Los Angeles, evaluated the methylation patterns of thousands of test subjects and used them to develop the “epigenetic clock”. Similar to telomeres, methylation patterns also serve to determine biological age, in contrast to chronological age.

Our laboratory partner Cerascreen, for example. In 2018, he developed the Genetic Age Test together with the Fraunhofer Institute, which measures biological age based on methylation patterns: https://qidosha.com/products/dna-biologisches-alter-test-inkl-analyse-durch-fachlabor-handlungsempfehlung?_pos=1&_sid=134b31ef8&_ss=r&variant=41732031905962

The question relevant to longevity approaches is whether and, if so, how these methylation patterns can be influenced in order to turn back the epigenetic clock.

It is known that stress, smoking and obesity have a negative effect on methylation patterns. Similarly, reducing stress can also restore the original methylation. And according to epigeneticist Prof. Isabelle Mansuy from the University of Zurich counteract the reduction in methylation: this is how broccoli works or the sulforaphane it contains and v.a green tea as “methyl donors”. The epigenetic clock can actually be turned back, it seems!

Which lifestyle factors are relevant for a long and healthy life?

 

1. Nutrition

Not surprisingly, fresh organic vegetables are good for healthy longevity. However, it is less about the harmfulness of pesticides for the body in conventionally grown vegetables, but more about the fact that plants had to deal with fungi, bacteria, harsh climates, etc. without the help of protective agents and are therefore much richer in the for the longevity of such important secondary plant substances are, for example. This is the case with greenhouse or conventionally grown vegetables.

A diet rich in fiber (mushrooms, berries, oatmeal, etc.) is also recommended.), as fiber as prebiotics is “food” for our intestinal bacteria. If the diet is low in fiber, the intestinal bacteria use the intestinal mucosa as a substitute food, so that antigens can more easily enter the body and trigger chronic inflammation, autoimmune diseases or allergies. If this is already the case, the medicinal mushroom Hericium is ideal for rebuilding the mucus layer - see also https://qidosha.com/blogs/qidosha-academy/vitalpilze

The often promoted “low carb”, on the other hand, does not generally make sense, because long-chain carbohydrates, which are contained in many vegetables, are very positive for healthy longevity. Low carb makes sense when there is no sugar, i.e.H short-chain carbohydrates, because sugar and.a through the formation of AGE (Advanced Glycation Endproducts) is not conducive to healthy longevity.

AGE are caused by the permanent attachment of glucose to protein and fat compounds. As a result, blood vessels lose their elasticity, muscles lose their ability to stretch, the skin becomes wrinkled - everything “sticks together” and becomes rigid. In addition, AGE oxidizes LDL particles (low density lipoprotein = the “bad cholesterol” in contrast to HDL) to form free radicals that damage the vessel walls. In addition, oxidized LDL particles no longer enter the cells and remain in the blood, which increases cholesterol levels and thus the risk of hardening of the arteries.

It is also important to largely avoid highly processed foods, because there are additives such as: contain the binder CMC (carboxylmethylcellulose), which damages the barrier function of the intestinal mucosa. They also often contain a lot of fat and sugar and little fiber, secondary plant substances, omega 3 fatty acids and micronutrients.

And last but not least the above-mentioned caloric restriction - fasting: this forces the cells to autophagy, which decreases with age so that cellular waste can accumulate . The “recycling” of cellular waste is initiated whenever food no longer provides enough fuel for the mitochondria. The disposal of cellular waste is therefore a desired side effect of fasting.

The first systematic study of the positive effects of caloric restriction dates from 1937 by Clive McCay: a 33% caloric restriction in laboratory rats has a) a significant extension of the maximum lifespan and b) an extension of the average lifespan by 50 % effected.

Polyphenols

A diet rich in polyphenols is of paramount importance for healthy longevity, so this topic will be discussed in a separate section.

Polyphenols are actually part of the plant defense. Quercetin seems particularly promising because it activates the longevity enzyme Sirtuin 6; but also to OPC, Curcumin and EGCG (epigallocatechin gallate) in green tea there are promising studies.

Strictly speaking, polyphenols are oxidants, not anti-oxidants, as they initially increase the production of free radicals and thus increase the cellular “radical defense” (e.g. Activate catalases - almost like a vaccination. The activated proteins and enzymes of the radical defense not only render oxygen radicals harmless, but as a side effect enzymes are also formed that

• work against chronic inflammatory processes
• maintain muscle mass
• Examine the DNA for completeness and repair if necessary

Green tea contains the highest concentration of EGCG in the plant kingdom, whose positive effect on longevity has been shown in epidemiological studies (that is, observational studies under real conditions - no experimental studies under laboratory conditions) could be proven. These studies suggest the following effects of EGCG:

• reduces the increase in blood sugar levels after carbohydrate-rich meals
• has an anti-inflammatory effect
• lowers cholesterol levels and increases the elasticity of blood vessels
• inhibits the formation of tumor blood vessels and the growth of polyps in the intestine

EGCG should, however, always be consumed as a tea and not as an extract in the form of a dietary supplement, otherwise it may...a the liver could be put under too much strain due to the high concentration.

2. Sleep

There are 4 deep sleep phases (in different stages) that we should achieve. On the one hand, little energy (ATP) is used in deep sleep, and on the other hand, our glymphatic system (the brain lymph, the “flushing system” of our brain, which removes harmful substances) is only active when we sleep. During sleep, the nerve cells in the brain “shrink”, so that the space between the cells increases and toxic substances, such as:a Beta-amyloids (precursors to Alzheimer's plaques = insoluble deposits between the nerve cells) can also be washed away more easily.

Receptors in the brain determine the day/night rhythm and our sleep depth - and unfortunately are not renewed, i.e.H they age. In addition, the level of melatonin produced by the pineal gland decreases with age, so that the deep sleep phases are often only achieved for a short time in older people.

This means that with fewer and shorter deep sleep phases, less energy in the form of ATP is available than in young people and the “flushing system” of the brain lymph described above can no longer function optimally, which leads to the formation of beta -Amyloids and thus Alzheimer's plaques.

Cortisol plays an important role in connection with poor sleep and its impact on healthy longevity. Cortisol is known as the so-called “stress hormone”. Cortisol is produced in the adrenal cortex from its inactive form, cortisone. Cortisol ensures, among other things,a also ensures that we wake up in the morning. It rises sharply in the morning and then falls more and more as the day progresses.

But if we sleep poorly, the cortisol level rises less in the morning than with good sleep, in which the deep sleep phases are reached. This is problematic because a decrease in cortisol can trigger or intensify inflammatory processes (the inactive form of cortisone is known to many for the treatment of inflammatory diseases). In this context one also speaks of “InflammAging”:

As people age, their body's own defenses also age: the immune system acquired over the course of life against pathogens with which the person has come into contact gradually shuts down; The innate, non-specific immune system, on the other hand, becomes overactive. This is v.a on the macrophages, which release inflammatory messengers in an uncontrolled manner when there is a cortisol deficiency. The result is chronic inflammation such as atherosclerosis or arthritis.

3. Movement/Muscle Strength

From the age of 60 As you age, muscle mass decreases and muscle fibers are increasingly replaced by fat and connective tissue. That's what v.a three central causes:

• The muscle-building hormones (v.a the growth hormone STH) decrease drastically.
• The proteins that are important for building muscle are no longer absorbed as well by the intestine.
• The nerves that activate the muscle fibers (motor neurons) die.

This leads to age-related muscle loss and frailty - clear signs of secondary aging.

Part of a holistic longevity approach must therefore be to maintain muscle mass as best as possible in old age. Strength training and a good night's sleep (seeO) is therefore essential because both stimulate STH release.

In addition, endurance training is necessary to activate or Training of the mitochondria relevant. Because in short competitive sports, the energy is obtained directly from short-chain carbohydrates (sugar) - it therefore does not train the mitochondria.

Essential amino acids such as Leucine and the combination of vitamin D3 & K2 are also important for muscle and bone health.

 

 

4. Reactivation of the thymus in old age

The thymus is a tiny organ in which our T cells are produced. T cells recognize antigens and their own body cells that are infected by viruses and kill them. From ~60. However, the thymus stops functioning as we age, so the immune system becomes weaker as we get older. Until recently, science believed that the thymus could not be generated. This seems to be changing now:

In the so-called TRIIM study (Thymus Regeneration Immune Restoration and Insulin Mitigation) by Dr. Greg Fahy, the test subjects were given a mix of zinc (approx. 50 mg), vitamin D (50-70 mcg/ml), metformin (actually a diabetes medication) for a year inhibits glucose formation in the liver, so that blood sugar levels fall; it slows down the process by which the mitochondria extract their energy from nutrients) and the sex hormone precursor DHEA. The result: the thymus has regenerated and the biological age has decreased by an average of 2.5 years! Since only 9 test subjects took part due to the high costs, all of them men, a new study with 85 test subjects has now been launched (TRIIM-X) - the results are expected at the end of 2022. If the results of the first study are even remotely confirmed, it would be an absolute sensation and a milestone in longevity research.