In an 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 infirmity at the end of life avoid it or at least significantly shorten it and extend as much as possible the period of life that we can enjoy in the best of health ("Healthspan").

Why are people getting older today than they used to?

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

Inhabitants of Germany who are 100 years 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%

Some aging researchers, however, doubt whether the maximum age that can be reached, 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 age was Jeanne Calment from France, who was born in 1875 and died in 1997. She was exactly 122 years and 164 days old. This means that since the year of their birth there has not been anyone who has aged despite all hygienic and medical advances. This suggests that the maximum human lifespan is around 120 years.

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

Of particular interest to the Longevity researchers are the so-called “blue zones”, in which a conspicuous 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 all their lives, especially little meat (but not vegetarian), exercised regularly but moderately - and they all had up to strong social bonds at the end of life.

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

Long-term stress also makes you age faster, because then more damaging stress hormones are released.

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

It seems that stress and diet in particular stand in the way of a particularly high longevity in Germany.

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

So-called "primary aging" begins around the age of 25.Year of life: by ~1% pa. the cell performance or cell competencies decrease. 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 already decreases at the age of 15, close vision decreases at the age of 40 and there is a risk of cataracts 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 becomes smaller
• Reproductive organs: from the age of 25 the fertility of women decreases, in men the testosterone level falls
• 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 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 the ages of 30 and 40, bone loss begins to outweigh the formation, so that an 80-year-old only has about 50% of the maximum bone substance
• Muscles: muscle loss begins from the age of 40 - a 65-year-old has about 10 kg less muscle mass than a 25-year-old
• Kidneys: at the age of 50, the filtration capacity decreases, so that blood purification takes longer and is less effective
• Brain: from the age of 60, the ability to react decreases, the ability to coordinate and the memory deteriorate
• Heart: at the age of 65, the heart can show signs of senility because, for example, the blood vessels calcify and the heart 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, the so-called "secondary aging" usually becomes noticeable in the form of typical age-related diseases such as arthrosis, stroke, heart attack, dementia, etc.

The care and cost-intensive illnesses will therefore increase dramatically, so that health in old age is becoming more and more important both from an individual and from a social point of view. Irrespective of the controversial question of whether aging is a disease, it is important, as with all health issues, not to fight the symptoms of aging with medication, but to focus on the causes of aging

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

What happens to a cell as it ages?

In order to understand what happens to a cell as it ages, we first need to understand what the core cell functions are. One also speaks here of the so-called "cell competencies" - a concept that goes back to Dr. Thrusher goes back:

1. renewal

The number of divisions that a body cell can undergo is limited. As a result, most of our cells will eventually need to be replaced.

Around 50 million cells per second (!) are exchanged in our body. Almost all 30 trillion body cells are replaced within 7 years.

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, when cells divide, the stem cell DNA must be copied with absolutely no errors. Therefore, keeping the stem cells healthy is particularly important for a healthy longevity.

But at some point the stem cell reservoir will be exhausted and there will be no more supplies. In addition, hematopoietic stem cells can mutate in old age and then remain in the blood as pro-inflammatory clones.

The freshwater polyp Hydra has therefore aroused particular interest of the Longevity scientists, because its stem cells are permanently active, so that old cells can always be replaced.

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

The cell types that are not renewed or are only slightly renewed include: nerve, heart muscle and sensory cells (eyes, ears). We cannot stop their aging, so that longevity approaches must focus primarily 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 consumes, the more mitochondria it usually has. A cardiac muscle cell, for example, has 5000 mitochondria!

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

From the age of 25, however, the mitochondria already lose their performance; i.e. with the same oxygen consumption, the ATP production decreases, so the mitochondria become less efficient. In old age, the mitochondrial performance has decreased by about 50% (!) - which is partly due 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.

More and more free radicals form in the mitochondria as waste products, which damage genetic material, organs, connective tissue, etc.

Disorders 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-medizin/?tx_jedcookies_main%5Baction%5D=submit&cHash=2ee0704321cb47f67169ef63d0c1c3d3

Therefore, longevity approaches must above all 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 the deficiency, e.g. with food supplements:

• Coenzyme Q10 (as a redox system (ubiquinone/ubiquinol) central component of the mitochondrial electron transport chain)
• L-carnitine (is mainly taken in with food (meat) and transports fatty acids through the mitochondrial membrane; in 2002, a study by the University of Leipzig in vivo demonstrated that L-carnitine reduces 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 East Africans, for example, when it comes to the performance of our mitochondria.This is due to evolution: due to the nomadic way of life, East Africans had to walk 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 carries on into old age. In this context, reference is often made to Churchill, who was a competitive athlete when he was young and who, even in old age, benefited from his well-trained mitochondria for a long time, despite a very unhealthy lifestyle.

3. detoxification

Cellular waste is constantly being produced as part of cell metabolism, such as errors in protein synthesis (misfolded proteins) or damaged parts of the mitochondria. This waste is normally broken down by cellular cleansing processes, primarily by what is known as autophagy, the cellular “recycling system”. The lysosomes then dock onto these waste products, and their enzymes break this waste down into its individual components, making it recyclable. Lysosomes are therefore also referred to as the "stomach" of our cells.

Unfortunately, in old age, this autophagy no longer works so well, so that molecular garbage 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). Because when food is scarce, the body activates autophagy to release nutrients from the "protein waste". And quasi 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 laboratory animals has prolonged life and counteracts aging processes.

theories of aging

1. program theories
2. a) shortening of the telomeres

The telomeres are the protective caps at the ends of the chromosomes. With each cell division, 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 the telomeres is increased by various factors, such as oxidative stress or chronic inflammation. The good news: Studies indicate that telomeres can also lengthen again. There are promising studies 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 specific lifetime in evolution? Because the conservation of the species is evolutionarily the most important thing. So evolution roughly calibrates lifespans to allow for rearing and sexual maturity.

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

Therefore, those hormones that are necessary 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 preserved and multiply without differentiating too much. that are urgently needed.

2. Damage Theories

Damage theories target free radicals. Free radicals have an unbonded pair of electrons and are therefore particularly aggressive as they try to snatch an electron from other molecules. In doing so, they are reduced and oxidize the other molecule, which itself becomes a free radical. A chain reaction is set in motion.

Free radicals damage tissue and the DNA of our cells, contributing to the aging process and the development of disease. They arise from

• 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 start with the defusing of free radicals. This is done by so-called antioxidants. We have an endogenous, enzymatic antioxidant system, but it is not always sufficient to effectively defuse all free radicals. Therefore, antioxidants should be supplied from the outside - either through food or highly concentrated 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 in old age genetically determined?

1. A) Genetics

Everyone knows stories like that of Helmut Schmidt, who has grown very old despite a very unhealthy lifestyle (e.g. chain smoker) - whereas others who live a very healthy life die young. Usually the genes are given as a reason.

Researchers are interested in this context, among other things, in the question of whether there is a longevity gene - the "Methusalem gene", so to speak. And indeed, there is the so-called FOX03 protein, which appears to activate the increase in the enzyme sirtuin 1, which is important for longevity. Everyone has this protein - but two specific variants/expressions of FOX03 are conspicuously common in people over 100 years of age. This was discovered in 2009 by the "Healthy Aging" research group at the University of Kiel. These variants of the FOX03 gene were also found in the above-mentioned freshwater polyps, whose stem cells are constantly renewed.

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 over 90-year-olds and found that at very old age the further survival increased to 75 % depends on good genes. I.e. only 25% of survival depends on lifestyle factors. However, it cannot be concluded from this that our fate in relation to our life expectancy is 75% genetically predetermined, because the above-mentioned 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 does not only include those people who have already reached a very old age is that of Dr. Graham Ruby, who compiled Ancestry data (Ancestry is the world's largest platform for genealogical research) from around 54 million people and their approx.evaluated 6 billion ancestors. And then a completely different picture emerges: the heritability of the lifespan seems to be only a maximum of 7%.

1. B) Epigenetics

Whereas genetics deals with DNA as the basic genetic equipment that is identical in all our cells, epigenetics deals with the activity state of our genes. Because the fact that our ~250 cell types function so differently, although the DNA is identical, is due to epigenetics, which controls the switching on and off of the genes.

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

How exactly does switching on/off work? About the so-called “methylation”: Methyl groups are molecules made up of one carbon and three hydrogen atoms and are attached to certain parts of the DNA – namely only where the DNA building block group CpG (cytosine-guanine) occurs, where they prevent certain gene sequences from being read , i.e. “turn off genes”.

As we age, methylation decreases, which means that genes that are not supposed to be active are also active and produce proteins that are not needed at all 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 subjects and used them to develop the "epigenetic clock". Similar to the telomeres, the methylation patterns are therefore also used to determine biological age, in contrast to chronological age.

Our laboratory partner Cerascreen, for example, developed the Genetic Age Test in 2018 together with the Fraunhofer Institute, which measures biological age based on the methylation pattern: https://qidosha.com/products/dna-biologisches -alter-test-incl-analysis-by-specialist-laboratory-recommendation?_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, obesity have a negative effect on the methylation pattern. Analogously, however, reducing stress can also restore the original methylation. According to the epigeneticist Prof. Isabelle Mansuy from the University of Zurich, nutrition can also counteract the reduction in methylation: this is how broccoli or the sulforaphane it contains and v.a. green tea as “methyl donors”. The epigenetic clock can therefore actually be turned back, it seems!

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

1. Nutrition

Unsurprisingly, 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 rather about the fact that plants had to deal with fungi, bacteria, harsh climate etc. without the help of preservatives and are therefore much richer in the for the longevity of phytochemicals that are so important than, for example, greenhouse or conventionally grown vegetables.

Eating a high-fiber diet (mushrooms, berries, oatmeal, etc.) is also recommended.), since dietary fiber as prebiotics is "food" for our intestinal bacteria In a diet low in dietary fiber, the intestinal bacteria use the intestinal mucosa as substitute food, so that antigens can get into the body more easily and cause chronic inflammation there, 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”, 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 it refers to sugar, i.e. short-chain carbohydrates, since sugar is not conducive to healthy longevity due to the formation of AGE (advanced glycation end products).

AGEs are caused by the permanent accumulation of glucose in protein and fat compounds. As a result, blood vessels lose their elasticity, muscles their ability to stretch, the skin becomes wrinkled - everything "sticks together", becomes rigid. In addition, AGE 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 get into the cells and remain in the blood, which increases the cholesterol level and thus the risk of arteriosclerosis.

It is also important to avoid highly processed foods, because there are additives such as the binder CMC (carboxylmethylcellulose) contain substances that damage the barrier function of the intestinal mucosa. In addition, they often contain a lot of fat and sugar and little dietary fiber, phytochemicals, omega 3 fatty acids and micronutrients.

And last but not least, the caloric restriction already mentioned above – fasting: this forces the cells to autophagy, which decreases with age so that cellular waste can accumulate . The "recycling" of cellular waste is always set in motion when the diet no longer provides enough fuel for the mitochondria. The disposal of cellular waste is thus a desirable side effect of fasting.

The first systematic study of the beneficial effects of caloric restriction was by Clive McCay in 1937: a 33% caloric restriction in laboratory rats resulted in a) a significant increase in maximum lifespan and b) a 50-year increase in average lifespan % causes.

polyphenols

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

Polyphenols are actually part of the plant's defences. Quercetin appears to be 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 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 enzymes are formed as a side effect, which

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

Green tea contains the highest concentration of EGCG in the plant kingdom, its positive effect on longevity in epidemiological studies (these are observational studies under real conditions - no experimental studies under laboratory conditions) 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 the high concentration could put too much strain on the liver.

2. sleep

There are 4 deep sleep phases (in different levels) that we should achieve. On the one hand, little energy (ATP) is consumed during deep sleep, and on the other hand, our glymphatic system (the cerebral lymph, the "flushing system" of our brain that drains pollutants, so to speak) is only active during sleep. During sleep, the nerve cells in the brain "shrink", so that the cell gap 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 our depth of sleep - and unfortunately they 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 in older people are often only reached for a short time.

As a result, with fewer and shorter deep sleep phases, less energy is available in the form of ATP 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 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 ensures, among other things, that we soften in the morning. It rises sharply in the morning and then falls more and more as the day progresses.

But if we sleep badly, 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 decrease in cortisol can trigger or exacerbate inflammatory processes (the inactive form of cortisone is known to many to treat inflammatory diseases). In this context one also speaks of "InflammAging":

When people age, their body's defenses also age: the immune system against pathogens that people have come into contact with, which they have acquired over the course of their lives, gradually shuts down; 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 consequences are chronic inflammations such as atherosclerosis or arthritis.

3. Movement/muscular power

From the age of 60, muscle mass decreases and muscle fibers are increasingly replaced by fat and connective tissue. There are three main reasons for this:

• The muscle-building hormones (especially the growth hormone STH) decrease drastically.
• The proteins that are important for building muscle are no longer as well absorbed by the intestines.
• The nerves that activate 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 preserve muscle mass as much as possible in old age. Strength training and a good night's sleep (see above) are therefore essential, because both stimulate STH release.

Endurance training is also relevant for activating or training the mitochondria. Because in short-term 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 where our T cells are produced. T-cells recognize antigens and virus-infected body cells and kill them. From the ~60. However, the thymus stops functioning as we age, so that the immune system weakens with age. Until recently, scientists 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 subjects took a mix of zinc (about 50 mg), vitamin D (50-70 mcg/ml), metformin (actually a diabetes drug that inhibits the formation of glucose in the liver, causing blood sugar levels to drop; 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 men, a new study with 85 subjects has now been launched (TRIIM-X) - the results are expected by the end of 2022. If the results of the first study are even approximately confirmed, it would be an absolute sensation and a milestone in longevity research.

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