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. This is not primarily about simply extending the maximum lifespan (“Lifespan”) or even about “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 aged 100 and over (Source: Stat. BA, Human Mortality Database, Robert Bosch Stiftung):

• 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 attainable age, the so-called maximum lifespan, can be extended. Unlike average life expectancy, the maximum has barely increased:

The person with the highest documented life expectancy was the Frenchwoman Jeanne Calment, who was born in 1875 and died in 1997 and lived to the age of exactly 122 years and 164 days. D.h. Since their birth, no one has lived to an old age, despite all the advances in hygiene and medicine. This suggests that the maximum human lifespan 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," where 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 elderly there have eaten healthy food throughout their lives, v.a. ate little meat (but not vegetarian), exercised regularly but moderately – and they all had strong social ties until the end of their lives.

According to a 2010 US meta-study, people with many social contacts have an approximately 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—since lonely people are more likely to smoke, 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, the “Blue Zones” have been found to have strikingly high levels of spermidine in their blood. Spermidine is absorbed through food (plants produce it v.a. in stressful situations) and also produced in the body itself (v.a. by the microbiome in the gut). Spermide stimulates autophagy, d.h. the cellular "recycling process." Fermented soy (Japanese natto), nuts, mushrooms, wheat germ, old/aged cheeses, and green vegetables are particularly rich in spermidine. All are found in the cuisine of the Blue Zones of Japan, Italy, and France.

It therefore seems that v.a. stress and diet in Germany are hindering particularly high longevity.

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

The so-called “primary aging” starts around the age of 25: by ~1% p.a. Cell performance or cell competence decreases. This, of course, only affects those cells that are not renewed. For example, the stem cells that are important for longevity are not renewed.

Examples:

• Eyes: already at 15 years of age the elasticity of the lens decreases, at 40 years of age the ability to see close up decreases and in old age cataracts are a threat
• Ears: ~From the age of 20, the number of hair cells in the cochlea, which are important for the perception of sound, decreases. Age-related hearing loss often sets in after the age of 60.
• Lungs: at the age of 20, the production of alveoli decreases; as the elasticity of the lungs also 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 retain 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 has only 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 the age of 50, filtration performance decreases, so that blood purification takes longer and is less effective
• Brain: from the age of 60, reaction time decreases, coordination skills and memory deteriorate
• Heart: at the age of 65, the heart may show signs of age-related weakness because, for example, the blood vessels calcify and the heart therefore has to pump against greater resistance
• Immune system: at 65, susceptibility to infections increases as the number of defense cells in the blood decreases

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

Care-intensive and cost-intensive illnesses will therefore increase dramatically, making health in old age increasingly important from both an individual and 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 to focus on the causes of aging.

Furthermore, most longevity approaches are not primarily concerned with extending the maximum lifespan, but rather with postponing secondary aging as far as possible. D.h. healthy aging is the focus.

What happens to a cell when it ages?

To understand what happens to a cell as it ages, we first need to understand the core cellular functions. These are also referred to as "cellular competencies"—a concept that dates back to Dr. Druscher:

1. renewal

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

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

For this cell renewal v.a. our stem cells. 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, stem cell DNA must be copied absolutely error-free during cell division. Therefore, maintaining healthy stem cells is particularly important for healthy longevity.

But at some point, the stem cell reservoir becomes exhausted, and no more new cells arrive. Furthermore, blood-forming stem cells can mutate with age and then remain in the blood as inflammatory clones.

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

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

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

2. Energy generation

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 heart muscle cell, for example, has 5,000 mitochondria!

Even at rest, the body needs approximately as many kilograms 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; d.h. With the same oxygen consumption, ATP production decreases, thus the mitochondria become less efficient. In old age, mitochondrial performance decreases 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.

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 v.a. 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 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 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 though we can and should influence mitochondrial performance in this way, there are still 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 match the mitochondrial energy production 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 at a young age, persists 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 continually produces cellular waste, such as errors in protein synthesis (misfolded proteins) or damaged mitochondrial fragments. This waste is normally eliminated through cellular cleaning processes. v.a. through so-called autophagy, the cellular "recycling system." Lysosomes then attach to these waste products, whose enzymes break this waste down into its individual components, making it reusable. Lysosomes are therefore also referred to as the "stomach" of our cells.

Unfortunately, as we age, this autophagy function no longer functions as well, so molecular waste accumulates in the cells and ultimately impairs normal cellular functions. Over the years, this cellular waste can then contribute to the relevant diseases of aging, 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 degraded. This also fits well with the observation in numerous studies that caloric restriction has prolonged lifespan in laboratory animals 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 with 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 v.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 the preservation of the species is evolutionarily most important. Therefore, evolution calibrates lifespans roughly to ensure 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 decisive influence on lifespan. For example, estradiol, which is not only a sex hormone but also ensures that stem cells are preserved in the bone marrow and proliferate without undergoing excessive differentiation. 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, contributing to the aging process and the development of diseases. They are caused by

• Chronic/silent inflammation
• 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 neutralizing free radicals. This is achieved through so-called antioxidants. We have our own enzymatic antioxidant system, but this 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 supplements. Among 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 despite a very unhealthy lifestyle (u.a. chain smoker) has lived to a very old age – whereas others who live very healthy lives die early. Here, i.d.R. genes were cited as the reason.

In this context, researchers are interested u.a. for the question of whether there is a single longevity gene – the "Methuselah 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/forms of FOX03 are strikingly common in people over 100 years old. This was discovered in 2009 by the "Healthy Aging" research group at Kiel University. o.gThese 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 1900 people over 90 and found that at a very old age more Survival depends 75% on good genes. D.h. only 25% of survival depends on lifestyle factors. However, this does not mean that our fate regarding our life expectancy is 75% genetically determined, because the o.g. study refers explicitly only to the further life expectancy of all those who have already reached a very old age (>= 90 years).

A study that doesn't just include people 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 research) of around 54 million people and their approximately 6 billion ancestors. The results reveal a very 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 material that is identical in all our cells, epigenetics is concerned with the activity state of our genes. The fact that our approximately 250 cell types function so differently, despite their 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 nearly identical epigenetic patterns at birth, which remain similar even in old age if their lifestyles are similar, but diverge just as significantly if their lifestyles are very different.

How exactly does the switching on/off work? It's done via "methylation": Methyl groups are molecules consisting of one carbon and three hydrogen atoms and attach themselves to specific DNA sites—namely, only where the DNA building block group CpG (cytosine-guanine) occurs—and prevent the reading of certain gene sequences. d.h. “switch off genes”.

Methylation decreases with age, which leads to genes being active that are not supposed to be active and producing proteins that are not needed or can even cause harmful effects, 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 test subjects and derived the “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 impact on methylation patterns. Similarly, reducing stress can also restore the original methylation. And according to epigeneticist Prof.Isabelle Mansuy from the University of Zurich counteracts the reduction of 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 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 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. 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 excellent for rebuilding the mucus layer – see also https://qidosha.com/blogs/qidosha-academy/vitalpilze

The often-promoted "low-carb" diet, however, is not generally sensible, as long-chain carbohydrates, which are found in many vegetables, are very beneficial for healthy longevity. Low-carb makes sense when it comes to avoiding sugar, d.h. short-chain carbohydrates, since Sugar u.a. through the formation of AGE (Advanced Glycation Endproducts) is not conducive to healthy longevity.

AGEs are formed by the persistent accumulation of glucose in protein and fat compounds. As a result, blood vessels lose their elasticity, muscles lose their ability to stretch, and skin wrinkles—everything "sticks together" and becomes rigid. AGEs also oxidize LDL particles (low-density lipoprotein, the "bad cholesterol" as opposed to HDL) into free radicals that damage blood vessel walls. Furthermore, oxidized LDL particles no longer enter the cells and remain in the blood, increasing cholesterol levels and thus the risk of arteriosclerosis.

It is also important to ensure Avoid highly processed foods, because there are additives such as Binder CMC (Carboxylmethylcellulose), which damages the barrier function of the intestinal mucosa. They also often contain high levels of fat and sugar and low levels of fiber, phytochemicals, omega-3 fatty acids, and micronutrients.

And last but not least the above mentioned caloric restriction – Fasting: This forces cells to undergo autophagy, which 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 disposal of cellular waste is thus 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 extension of maximum lifespan and b) an extension of average lifespan by 50%.

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. 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 neutralize oxygen radicals, but also, as a side effect, produce enzymes that

• work 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 kingdom, whose positive effect on longevity has 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
• 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, otherwise u.a. the liver could be put under too much strain due to the high concentration.

2. Sleep

There are four deep sleep phases (of varying intensity) that we should achieve. Firstly, little energy (ATP) is consumed during deep sleep, and secondly, our glymphatic system (the cerebral lymph, our brain's "flushing system" that removes toxins) is only active during sleep. During sleep, the nerve cells in the brain “shrink”, so that the space between the cells increases and toxic substances, such as u.a. also beta-amyloids (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 are unfortunately not renewed, d.h. they age. In addition, the level of melatonin produced by the pineal gland decreases with age, so that older people often only reach deep sleep phases for short periods.

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 "stress hormone." Cortisol is produced in the adrenal cortex from its inactive form, cortisone. Cortisol ensures u.a. also ensures that we soften in the morning. It rises sharply in the morning and then falls steadily throughout the day.

But if we sleep badly, the cortisol level rises less in the morning than during 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, so does their body's defenses: 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. v.a. on the macrophages, which uncontrollably release inflammatory messengers when cortisol is deficient. 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. v.a. three central causes:

• The muscle-building hormones (v.a. the growth hormone STH) decrease drastically.
• The proteins important for muscle building are no longer absorbed as well by 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 (s.o.) is therefore essential, because 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 derived directly from short-chain carbohydrates (sugar), so it doesn't train the mitochondria.

Essential amino acids such as leucine and the combination of vitamins D3 and 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 the body's own cells infected by viruses and kill them. However, from the age of 60 onward, 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, the subjects were given a mix of Zinc (approx. 50 mg), vitamin D (50-70 mcg/ml), metformin (actually a diabetes drug that inhibits glucose production 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! Because of the high costs, only nine subjects participated, all of them men, so 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 remotely confirmed, it would be an absolute sensation and a milestone in longevity research.