In an ageing society, health in old age plays an increasingly important role. For each individual, but also for society and the health system. This is not primarily about simply extending the maximum life span ("Lifespan") or even “immortality”, but rather about avoiding the unfortunately often long period of infirmity at the end of life or at least significantly shortening it and extending the period of life that we can enjoy in the best of health as far as possible ("Healthspan").

Why do people live longer today than in the past?

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 Stiftung):

• 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 life span, can be extended. Unlike the average life expectancy, the maximum has hardly increased:

The person with the highest documented life expectancy was the Frenchwoman Jeanne Calment, who was born in 1875 and died in 1997. She lived to the age of exactly 122 years and 164 days. This means that since the year she was born, no one has lived to an older age, despite all the advances in hygiene and medicine. This suggests that the maximum lifespan of humans is around 120 years.

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

Of particular interest to longevity researchers are the so-called “Blue Zones”, in which a strikingly high number of centenarians live. These include Sardinia and the Japanese island of Okinawa.

Studies on the causes of longevity in these zones have shown that the very old there have had a healthy diet throughout their lives, eating very little meat (but not vegetarian), exercising 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 many social contacts have a 50% lower risk of dying earlier than expected. Of course, loneliness has no direct physical impact, but it does have an indirect one - because lonely people smoke more often, are more likely to be overweight and are less physically active.

Long-term stress also causes us to age faster because it causes more damaging stress hormones to be released.

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

It therefore seems that stress and diet in particular are the obstacles to particularly high longevity in Germany.

Ageing processes begin at a young age: primary and secondary ageing

The so-called "primary aging" begins around the age of 25: cell performance and cell competence decrease by ~1% per year. Of course, this only affects those cells that are not renewed. For example, the stem cells that are relevant for longevity are not renewed.

Examples:

• Eyes: the elasticity of the lens decreases at the age of 15, near vision decreases at the age of 40 and cataracts threaten 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 from the age of 60
• Lungs: at the age of 20, the production of alveoli decreases; as the elasticity of the lungs decreases, the volume of air that can be inhaled and exhaled decreases
• Reproductive organs: from the age of 25, women’s fertility decreases, and men’s testosterone levels drop
• Joints: from the age of 30, the cartilage loses elasticity and the intervertebral discs become stiffer
• Skin: from the age of 30, the skin can bind less moisture and loses elasticity
• Hair: from the age of 30, the production of the pigment melanin decreases and then stops completely
• Bones: between 30 and 40 years, bone loss begins to outweigh bone formation, so that an 80-year-old only has about 50% of the maximum bone substance
• Muscles: muscle loss begins at the age of 40 – a 65-year-old has about 10 kg less muscle mass than a 25-year-old
• Kidneys: at age 50, filtration performance declines, so blood purification takes longer and is less effective
• Brain: from the age of 60, reaction time decreases, coordination and memory deteriorate
• Heart: at 65 years of age, the heart can show signs of old age because, for example, the blood vessels calcify and the heart therefore has to pump against greater resistance
• Immune system: at 65, susceptibility to infection increases as the number of defense cells in the blood decreases

In the sixties, the so-called "secondary aging" noticeable in the form of typical age-related diseases such as arthritis, stroke, heart attack, dementia, etc.

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

In addition, most longevity approaches are not primarily concerned with extending the maximum life span, but rather with delaying secondary aging as far as possible. In other words, healthy aging is the focus.

What happens to a cell when it ages?

In order to understand what happens to a cell when it ages, we first need to understand what central cell functions exist. This is also referred to as “cell competencies” – a concept that goes back to Dr. Druscher:

1. renewal

The number of divisions 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 replaced in our body. Within 7 years, almost all 30 trillion body cells are replaced.

Our stem cells are primarily responsible for this cell renewal. Stem cells are the reservoir for various body cells into which the stem cells can differentiate. The only 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, keeping the stem cells healthy is particularly important for healthy longevity.

But at some point the stem cell reservoir is exhausted and no more new cells arrive. In addition, blood-forming stem cells can mutate with age and then remain in the blood as inflammation-promoting clones.

The freshwater polyp Hydra has therefore 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 ​​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 these with new therapies and thus be able to prolong organ preservation in old age.

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

2. energy production

The energy for our cells is produced in the mitochondria, the power plants of our cells. The more energy a cell needs or uses, the more mitochondria it usually has. A heart muscle cell, for example, has 5,000 mitochondria!

Even at rest, the body needs about as many kg of ATP per day as our body weight! During physical activity, ATP production increases significantly.

However, from the age of 25, mitochondria begin to lose performance; that is, with the same oxygen consumption, ATP production decreases, meaning that mitochondria become less efficient. In old age, mitochondrial performance has decreased by around 50% (!) - which is due, among other things, to the fact that 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.

In addition, free radicals are increasingly formed in the mitochondria as waste products, which damage genetic material, organs, connective tissue, etc.

Diseases of the nervous system, such as Parkinson's disease, are 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 focus on the relevant factors in the citric acid cycle (upstream of the respiratory chain) and the respiratory chain or electron transport chain and try to fill deficiencies, e.g. through nutritional supplements:

• coenzyme Q10 (as a redox system (ubiquinone/ubiquinol) a central component of the mitochondrial electron transport chain)
• L-carnitine (is especiallyabsorbed 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 limits for us Europeans compared to, for example, East Africans when it comes to the performance of our mitochondria. This is due to evolution: due to their 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 come close to the energy production of the mitochondria of Kenyans or Ethiopians; which is why the latter regularly win marathons.

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

3. detoxification

Cellular metabolism constantly produces cellular waste, such as errors in protein synthesis (misfolded proteins) or damaged mitochondrial parts. This waste is normally broken down by cellular cleaning processes, especially by so-called autophagy, the cellular "recycling system". Lysosomes then attach themselves to these waste products, and their enzymes break this waste down into its individual components, making it reusable. Lysosomes are therefore also known as the "stomach" of our cells.

Unfortunately, as we age, this autophagy no longer works as well, so 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 through caloric restriction (fasting). When food is scarce, the body activates autophagy to release nutrients from the "protein waste." And as a side effect of this nutrient extraction, misfolded proteins and defective organelles are broken down. This also fits well with the observation in numerous studies that caloric restriction in experimental animals has prolonged life and counteracts aging processes.

Theories of Aging

1. program theories
2. a) Shortening of telomeres

Telomeres are the protective caps at the ends of chromosomes. They shorten by a defined number of base pairs during each cell division.

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, as opposed to chronological age.

Telomere shortening is exacerbated 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 especially 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 the preservation of the species is evolutionarily the most important thing. Therefore, evolution calibrates the lifespan in such a way that breeding and sexual maturity are guaranteed.

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 life expectancy. For example, estradiol, which is not only a sex hormone, but also ensures that the stem cells in the bone marrow are preserved 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 urgently needed.

2. damage theories

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

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

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

According to this theory, longevity measures must therefore focus on defusing free radicals. This is done through so-called antioxidants. We have our own enzymatic antioxidant system, but this 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 nutritional 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 in old age genetically predetermined?

1. A) Genetics

Everyone knows stories like that of Helmut Schmidt, who lived to a ripe old age despite a very unhealthy lifestyle (including chain smoking) – whereas others who lead very healthy lives die early. Genetics are usually cited as the reason.

In this context, researchers are interested in the question of whether there is a single longevity gene - the "Methuselah gene", so to speak. And there is indeed the so-called FOX03 protein, which seems to activate the increase in the enzyme Sirtuin 1, which is important for longevity. Everyone has this protein - but two specific variants/forms of FOX03 are strikingly common in people over 100 years old. This was discovered in 2009 by the "Healthy Aging" research group at the University of Kiel. The above-mentionedThese variants of the FOX03 gene were found in freshwater polyps, whose stem cells are constantly renewing themselves.

However, since the two variants of FOX03 only occur in very few people and 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 data from 1,900 people over 90 years of age and found that in very old age more Survival depends 75% on good genes. This means that only 25% of survival depends on lifestyle factors. However, this does not mean that our fate in terms of our life expectancy is 75% genetically predetermined, because the above study explicitly only refers to the life expectancy of all those who have already reached a very old age (>= 90 years).

A study that does not only include people who have already reached a very old age is that of Dr. Graham Ruby, who evaluated Ancestry data (Ancestry is the world's largest platform for genealogy research) of around 54 million people and their approximately 6 billion ancestors. And the result is a completely different picture: The heritability of lifespan appears to be only 7% at most to lie.

1. B) Epigenetics

While genetics deals with DNA as the basic genetic equipment that is identical in all of our cells, epigenetics is concerned with the activity state 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 on and off of genes.

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

How does the switching on/off work in practice? Via what is known as “methylation”: Methyl groups are molecules made up of one carbon and three hydrogen atoms and are located at certain points on the DNA - namely only where the DNA building block group CpG (cytosine-guanine) occurs, and prevent the reading of certain gene sequences there, ie “switch genes off”.

As we age, methylation decreases, which leads to genes that are not supposed to be active being active and producing proteins that are not needed or can even cause harm, such as inflammation..

Steve Horvath, a German professor of human genetics and biostatistics at the University of Los Angeles, has evaluated the methylation patterns of thousands of subjects and used them to determine "epigenetic clock" developed. Similar to telomeres, methylation patterns are used to determine biological age, as opposed to chronological age.

Our laboratory partner Cerascreen, for example, developed the Genetic Age Test together with the Fraunhofer Institute in 2018, 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 relevant question for longevity approaches is whether and, if so, how these methylation patterns can be influenced to turn back the epigenetic clock.

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

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

1. Nutrition

Not surprisingly, fresh organic vegetables good for healthy longevity. However, this is less about the harmfulness of pesticides to the body in conventionally grown vegetables, but rather 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 nutrients that are so important for longevity. secondary plant substances than is the case, for example, with greenhouse or conventionally grown vegetables.

A diet rich in fiber (mushrooms, berries, oatmeal, etc.) is also recommended, as fiber acts as prebiotics and “food” for our intestinal bacteria. When 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 propagated "low carb" is not generally sensible, because long-chain carbohydrates, which are contained in many vegetables, are very positive for healthy longevity. Low carb makes sense when it refers to sugar, ie short-chain carbohydrates, because Sugar, among other things, through the formation of AGE (Advanced Glycation Endproducts) is not conducive to healthy longevity.

AGEs are formed by the permanent accumulation of glucose in protein and fat compounds. This causes blood vessels to lose their elasticity, muscles to lose their ability to stretch, skin to become wrinkled - everything "sticks together" and becomes rigid. AGEs also oxidize 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 reach the cells and remain in the blood, which increases cholesterol levels and thus the risk of arteriosclerosis.

It is also important to have a broad Avoiding highly processed foods, because there are additives such as binder CMC (carboxylmethylcellulose), which damage the barrier function of the intestinal mucosa. In addition, they 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 undergo autophagy, which decreases with age, allowing cellular waste to accumulate. The "recycling" of cellular waste is always triggered when the diet 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 on the positive effects of caloric restriction dates back to 1937 by Clive McCay: a 33% caloric restriction in laboratory rats resulted in a) a significant extension of the maximum lifespan and b) an extension of the average lifespan by 50%.

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’s defense system. Particularly promising is quercetin 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 antioxidants, as they initially increase the production of free radicals and thus activate the cellular “radical defense” (e.g. catalases) - almost like a vaccination. The activated proteins and enzymes of the radical defense not only render oxygen radicals harmless, but also, as a side effect, enzymes are formed that

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

Green tea contains the highest EGCG concentration in the plant kingdom, whose positive effect on longevity has been demonstrated in epidemiological studies (these are observational studies under real conditions - not experimental studies under laboratory conditions). These studies suggest the following effects of EGCG:

• reduces the rise 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

However, EGCG should always be consumed as a tea and not as an extract in the form of a dietary supplement, as otherwise the liver, among other things, could be placed under too much strain due to the high concentration.

2. Sleep

There are 4 deep sleep phases (of varying degrees) that we should achieve. Firstly, little energy (ATP) is used in deep sleep, and secondly, our glymphatic system (the brain lymph, the "flushing system" of our brain that 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 beta-amyloids, (Precursors of Alzheimer's plaques = insoluble deposits between the nerve cells) can be washed away more easily.

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

As a result, 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 promotes the formation of beta-amyloids and thus Alzheimer's plaques.

Cortisol plays a significant role in 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 also makes us soft in the morning. It rises sharply in the morning and then falls steadily over the course of the day.

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 in that a Cortisol decline 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 defenses also age: the immune system acquired over the course of life against pathogens with which the person has come into contact gradually weakens; the innate, non-specific immune system, on the other hand, becomes overactive. This is mainly due to the macrophages, which uncontrollably release inflammatory messengers 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, muscle mass decreases and muscle fibers are increasingly replaced by fat and connective tissue. There are three main causes for this:

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

This leads to age-related muscle wasting 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 (see above) are therefore essential, as both stimulate the secretion of STH.

In addition, endurance training is important for activating or training the mitochondria. In short-duration competitive sports, 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 the body's own cells that are infected by viruses and kill them. However, from the age of 60 onwards, the thymus stops functioning, so that the immune system weakens with age. Until recently, science believed that the thymus could not be generated. This now seems to be changing:

In the so-called TRIIM study (Thymus Regeneration Immunrestoration and Insulin Mitigation) by Dr.Greg Fahy, the subjects were given a mix of Zinc (approx. 50 mg), vitamin D (50-70 mcg/ml), metformin (actually a diabetes drug that inhibits the production of glucose in the liver, so that blood sugar levels fall; it slows down the process by which the mitochondria extract 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 subjects took part due to the high costs, and all of them were men, a new study with 85 subjects has now been launched (TRIIM-X) - the results are expected for the end of 2022. If the results of the first study are even remotely confirmed, this would be an absolute sensation and a milestone in longevity research.