In an increasingly aging society, health in old age plays an ever more important role. This applies to every individual, but also to society and the healthcare system. It is not primarily about simply extending the maximum lifespan ("Lifespan") or even about "immortality", but rather about avoiding or at least significantly shortening the unfortunately often long period of decline at the end of life and extending as much as possible the phase of life that we can enjoy in the best of health. (Healthspan)).

Why are people living longer today than in the past?

In humans, external factors such as improved 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

Percentage 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 achievable age, the so-called maximum lifespan, can be extended. Unlike average life expectancy, maximum lifespan has hardly increased.

The person with the highest documented lifespan was the Frenchwoman Jeanne Calment, born in 1875 and died in 1997, who lived to be exactly 122 years and 164 days old. D.hSince their birth year, no one has lived longer than this, despite all hygienic and medical advances. This suggests that the maximum human lifespan is around 120 years.

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

Longevity researchers are particularly interested in the so-called "Blue Zones," where a remarkably high 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 elderly there have maintained a healthy diet throughout their lives. v.aThey ate little meat (though not vegetarian), exercised regularly but moderately – and they all maintained strong social bonds until the end of their lives.

According to a 2010 US meta-study, people with many social contacts have about a 50% lower risk of dying prematurely. Of course, loneliness has no direct physical effect, but it does have an indirect one – lonely people are more likely to smoke, are more likely to be overweight, and are less physically active.

Long-term stress also causes faster aging because it leads to an increased release of damaging stress hormones.

Furthermore, unusually high spermidine levels are measured in the blood in the "Blue Zones." Spermidine is ingested through food (plants produce it). v.a. in stressful situations itself) and also produced by the body itself (v.a. through the gut microbiome). Spermidne stimulates autophagy, d.h...the cellular "recycling process." Fermented soy (Japanese natto), nuts, mushrooms, wheat germ, aged cheeses, and green vegetables are particularly rich in spermidine. All are staples of the cuisine in the Blue Zones of Japan, Italy, and France.

It therefore seems that v.aStress and diet in Germany are obstacles to a particularly high lifespan.

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

The so-called “primary aging” It begins around the age of 25: by ~1% p.aCell function and cell competence decrease. This, of course, only affects those cells that are not renewed. Stem cells, for example, which are relevant for longevity, are not renewed.

Examples:

• Eyes: the elasticity of the lens decreases as early as age 15, near vision deteriorates by age 40, and cataracts threaten in old age.
• Ears: From around age 20, the number of hair cells in the cochlea, which are important for sound perception, decreases. Age-related hearing loss often sets in from age 60.
• Lungs: 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, a woman's fertility declines; in men, testosterone levels decrease.
• Joints: from the age of 30, cartilage loses elasticity and the intervertebral discs become stiffer.
• Skin: from age 30, the skin is less able to retain 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 bone formation, so that an 80-year-old has only about 50% of their maximum bone mass.
• 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 age 50, filtration capacity declines, so blood purification takes longer and is less effective.
• Brain: From age 60 onwards, reaction time, coordination and memory deteriorate.
• Heart: at age 65, the heart may show signs of age-related weakness, for example because the blood vessels calcify and the heart therefore has to pump against greater resistance.
• Immune system: at age 65, susceptibility to infection increases because the number of immune cells in the blood decreases.

In his sixties, this then becomes apparent i.d.R. 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 care-intensive and costly illnesses will therefore increase dramatically, making health in old age ever more 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, the key is not to combat the symptoms of aging with medication, but to focus on the underlying causes of aging.

Furthermore, most longevity approaches are not primarily about extending the maximum lifespan, but about postponing secondary aging as long as possible. D.hHealthy aging is the main focus.

What happens to a cell as it ages?

To understand what happens to a cell as it ages, we first need to understand its core functions. These are also referred to as "cellular competencies"—a concept originating with 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.

Approximately 50 million cells per second (!) are replaced in our bodies. Within 7 years, almost all 30 trillion body cells are replaced.

This cell renewal process requires v.aOur stem cells are responsible for this. Stem cells are the reservoir for various body cells into which they can differentiate. The problem is that our stem cells themselves are not replaced and therefore "age" by accumulating DNA damage that the repair systems cannot keep up with. However, stem cell DNA must be copied absolutely flawlessly during cell division. Therefore, maintaining the health of stem cells is particularly important for healthy longevity.

But eventually, the stem cell reservoir is depleted and no new cells are produced. Furthermore, blood-forming stem cells can mutate with age and then remain in the blood as pro-inflammatory clones.

Longevity scientists are therefore particularly interested in the freshwater polyp Hydra, 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 stem cell loss in old age, in order to inhibit these with new therapies and thus prolong organ preservation in old age.

Cell types that are not renewed or are only renewed to a limited extent include: u.aNerve cells, heart muscle cells, and sensory cells (eye, ear). We cannot stop their aging, so longevity approaches, alongside stem cell health, are crucial. v.a...must focus on these cell types.

2. Energy generation

The energy for our cells is produced in the mitochondria, the powerhouses of our cells. The more energy a cell needs or consumes, the more mitochondria it typically has. A heart muscle cell, for example, has 5000 mitochondria!

Even at rest, the body requires approximately as many kilograms of ATP daily as our body weight! During physical activity, ATP production increases significantly again.

However, from the age of 25, the mitochondria already begin to lose performance; d.hWith the same oxygen consumption, ATP production decreases, meaning the mitochondria become less efficient. In old age, mitochondrial performance is reduced by about 50% (!) – which u.aThis 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.

Furthermore, increased amounts of free radicals are formed in the mitochondria as waste products, which damage DNA, 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 be considered. v.aFocus 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 replenish deficiencies, e.g., through dietary supplements:

• Coenzyme Q10 (as a redox system (ubiquinone/ubiquinol) a central component of the mitochondrial electron transport chain)
• L-Carnitine (becomes v.a.Absorbed through food (meat) and transports fatty acids across 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.
• Vitamins B6, B9 (folic acid), and B12 as important cofactors

Even though we can and should influence mitochondrial performance in this way, there are limits for us Europeans compared to, for example, East Africans, regarding the efficiency of our mitochondria. This is due to evolution: because of 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 match the energy production of the mitochondria of Kenyans or Ethiopians; which is why the latter regularly win marathons.

But regardless of our evolutionary predisposition, we can train our mitochondria. And good mitochondrial fitness, acquired in youth, persists well into old age. In this context, Churchill is often cited; he was a competitive athlete in his youth and benefited from his well-trained mitochondria well into old age, despite a very unhealthy lifestyle.

3. detoxification

Cellular waste is constantly produced as part of cellular metabolism, such as errors in protein synthesis (misfolded proteins) or damaged mitochondrial fragments. This waste is normally broken down by cellular cleaning processes. v.a...through autophagy, the cellular "recycling system." Lysosomes then attach to these waste products, and their enzymes break down this waste into its individual components, making it reusable. Lysosomes are therefore also referred to as the "stomach" of our cells.

Unfortunately, this autophagy process doesn't function as well with age, leading to an accumulation of molecular waste in cells and eventually impairing normal cell functions. Over the years, this cellular waste can contribute to age-related diseases such as diabetes, Alzheimer's, and Parkinson's.

One way to activate autophagy is through caloric restriction (fasting). When food is scarce, the body activates autophagy to release nutrients from protein waste. As a side effect of this nutrient extraction, misfolded proteins and defective organelles are broken down. This aligns well with observations from numerous studies showing that caloric restriction has extended lifespan and counteracted aging processes in laboratory animals.

Theories about aging

1. Program theories
2. a) Shortening of telomeres

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

The shorter the telomeres, 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 telomeres is thus considered an indicator of so-called biological age, as opposed to chronological age.

The shortening of telomeres is intensified 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. v.a. for vitamins D, E, ginkgo and omega-3 fatty acidsSee 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 for a specific length of time in evolution? Because the preservation of the species is evolutionarily paramount. Therefore, evolution calibrates lifespans to ensure successful breeding and sexual maturity.

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

Therefore, the hormones required for reproduction also have a crucial influence on lifespan. For example, estradiol, which is not only a sex hormone but also ensures that stem cells in the bone marrow are maintained and multiply without differentiating too much. Only at the "site of action," 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 electron pair and are therefore particularly aggressive, as they attempt 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, thus contributing to the aging process and the development of diseases. They are produced 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 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 neutralizing free radicals. This is achieved through so-called antioxidants. We have our own enzymatic antioxidant system, but it is not always sufficient to effectively neutralize all free radicals. Therefore, antioxidants must be supplied externally – either through food or in highly concentrated form via suitable dietary supplements. Among the particularly effective... Antioxidants Examples of vitamins (measured by the so-called ORAC value) include 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, despite a very unhealthy lifestyle (u.aChain smokers have lived to a very old age – whereas others who live very healthy lives die young. Here, then, i.d.RThe genes were cited as the reason.

Researchers are interested in this context u.a...for the question of whether there is a single longevity gene – a kind of "Methuselah gene." And indeed, there is the so-called FOX03 protein, which appears to activate the increase of the enzyme sirtuin 1, important for longevity. Everyone has this protein – but two specific variants/expressions of FOX03 are strikingly common in centenarians. This was discovered in 2009 by the "Healthy Aging" research group at Kiel University. Also among the o.gThese variants of the FOX03 gene were found in freshwater polyps whose stem cells constantly renew themselves.

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

Another study, the "New England Centenarian Study", analyzed data from 1900 people over 90 years old and found that in very old age more Survival depends 75% on good genes. D.hOnly 25% of our continued survival depends on lifestyle factors. However, this does not mean that our fate regarding our life expectancy is 75% genetically predetermined, because the o.gThe study explicitly refers only to the remaining life expectancy of those who are already very old (&have become 90 years old.

One study that includes not only those who have already reached a very old age is that of Dr. Graham Ruby, who analyzed Ancestry data (Ancestry is the world's largest platform for genealogy) from approximately 54 million people and their roughly 6 billion ancestors. And the result is a completely different picture: The heritability of lifespan appears to be only a maximum of 7%. to lie down.

1. B) Epigenetics

While genetics deals with DNA as the basic genetic material, which is identical in all our cells, epigenetics focuses on the activity state of our genes. The fact that our approximately 250 cell types function so differently, despite having identical DNA, 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 they have similar lifestyles, but can diverge just as significantly if they have very different lifestyles.

How exactly does the switching on/off work? Via the so-called "methylation": Methyl groups are molecules consisting of one carbon and three hydrogen atoms and attach themselves to specific sites on the DNA - namely only where the DNA building block group CpG (cytosine-guanine) is present, and prevent the reading of certain gene sequences there. d.h"switch off genes".

Methylation decreases with age, which leads to genes becoming active that should not be active at all, 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, analyzed the methylation patterns of thousands of test subjects and derived from them the "epigenetic clock" developed. Similar to telomeres, methylation patterns are therefore 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 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 now whether and, if so, how these methylation patterns can be influenced to turn back the epigenetic clock.

It is known that stress, smoking, and being overweight negatively affect methylation patterns. Conversely, reducing stress can also restore the original methylation. And according to epigeneticist Prof.Isabelle Mansuy from the University of Zurich counteracts the reduction of methylations: This is how broccoli works or the sulforaphane it contains and v.a. green tea as a “methyl donor”It seems that the epigenetic clock can indeed be turned back!

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

1. Nutrition

Unsurprisingly, 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 without the help of protective agents had to cope with fungi, bacteria, harsh climates, etc., and are therefore much richer in the substances so important for longevity. secondary plant compounds are, for example, better than greenhouse-grown or conventionally grown vegetables.

A diet rich in fiber (mushrooms, berries, oatmeal, etc.) is also recommended, as fiber acts as prebiotics and is "food" for our intestinal bacteria. In diets low in fiber, gut bacteria use the intestinal mucosa as a substitute food source.This allows antigens to more easily enter the body and trigger chronic inflammation, autoimmune diseases, or allergies. If this is already the case, the medicinal mushroom Hericium is excellent for rebuilding the mucus layer – see also https://qidosha.com/blogs/qidosha-academy/vitalpilze

The often-touted "low carb" diet, on the other hand, is not generally advisable, because long-chain carbohydrates, which are found in many vegetables, are very beneficial for healthy longevity. Low carb is only useful when it comes to reducing sugar, d.hshort-chain carbohydrates, since Sugar u.a. through the formation of AGE (Advanced Glycation Endproducts) is not conducive to a healthy longevity.

AGEs are formed by the persistent binding of glucose to protein and fat compounds. This causes blood vessels to lose their elasticity, muscles to lose their extensibility, and skin to become wrinkled – everything becomes stiff and rigid. Furthermore, AGEs oxidize LDL particles (low-density lipoprotein, the "bad cholesterol" as opposed to HDL) into free radicals that damage the vessel walls. Oxidized LDL particles also prevent them from entering cells and remain in the bloodstream, thus raising cholesterol levels and increasing the risk of arteriosclerosis.

Furthermore, the extensive Avoiding highly processed foods, because it contains additives such as, for example, the Binder CMC They contain (carboxymethylcellulose), which damages the barrier function of the intestinal mucosa. In addition, they often contain a lot of fat and sugar and little fiber, phytochemicals, omega-3 fatty acids, and micronutrients.

And last but not least, the one already mentioned above. calorie restriction – Fasting: it forces cells to undergo autophagy, a process that declines with age, allowing cellular waste to accumulate. The "recycling" of cellular waste is triggered whenever food no longer provides enough fuel for the mitochondria. The removal of cellular waste is therefore a desirable 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 increase in maximum lifespan and b) a 50% increase in average lifespan.

Polyphenols

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

Polyphenols are actually part of the plant's defense system. They appear to be particularly promising. Quercetin to be, as 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, because they initially increase the production of free radicals and thus activate the cellular "free radical defense" (e.g., catalases) – much like a vaccination. The activated proteins and enzymes of the free radical defense not only neutralize oxygen radicals, but also, as a side effect, produce enzymes that

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

Green tea contains the highest EGCG concentration in the plant kingdomEGCG, whose positive effects on longevity have been demonstrated in epidemiological studies (observational studies under real-world 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
• It has an anti-inflammatory effect
• It 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 u.aThe liver could be overloaded due to the high concentration.

2. Sleep

There are four deep sleep phases (in varying degrees of intensity) that we should aim to achieve. This is because, firstly, little energy (ATP) is consumed during deep sleep, and secondly, our glymphatic system (the brain's lymphatic system, essentially the "flushing system" of our brain that removes toxins) is only active during sleep. During sleep, nerve cells in the brain "shrink," increasing the space between cells and allowing toxic substances, such as... u.a. also beta-amyloid (Precursors of Alzheimer's plaques = insoluble deposits between nerve cells) can be washed away more easily.

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

This results in fewer and shorter deep sleep phases, meaning less energy in the form of ATP is available compared to younger people, and the "flushing system" of the brain lymph described above can no longer function optimally, which promotes the formation of beta-amyloid and thus Alzheimer's plaques.

Cortisol plays a significant role in connection with poor sleep and its impact on longevity. Cortisol is known as the "stress hormone." It is produced in the adrenal cortex from its inactive form, cortisone. Cortisol ensures u.aThis also explains why we feel so soft in the mornings. It rises sharply in the morning and then falls more and more throughout the day.

However, if we sleep poorly, the cortisol level rises less sharply in the morning. as with good sleep, in which the deep sleep phases are reached. This is problematic insofar as a A decrease in cortisol can trigger or exacerbate inflammatory processes. (The inactive form of cortisone is well-known for treating inflammatory diseases). In this context, one also speaks of “InflammAging”:

As a person ages, so does their immune system: The immune system acquired over the course of a lifetime, which fights against pathogens with which the person has come into contact, gradually declines; the innate, non-specific immune system, on the other hand, becomes overactive. This is due to v.a...at the macrophages, which release inflammatory mediators uncontrollably when cortisol is deficient. This results in 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 reasons for this. v.a. three main causes:

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

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

Therefore, maintaining muscle mass as much as possible in old age must be part of a holistic longevity approach. Strength training and good night's sleep (s.o.) is therefore essential, because both stimulate STH release.

Furthermore, endurance training is relevant for activating and training the mitochondria. This is because short-term, high-intensity exercise derives energy directly from short-chain carbohydrates (sugars) – it therefore does not train the mitochondria.

Essential amino acids such as leucine, as well as the combination of vitamin D3 &K2 and K1 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 cells of the body and kill them. However, from around the age of 60, the thymus ceases to function, so the immune system weakens with age. Until recently, scientists believed that the thymus could not be regenerated. This now appears to be changing:

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