The Aging Process: Mechanisms

Slowing or reversing the ageng process has been a hot topic throughout human history. Aging can be defined as a system-wide decline in organismal function. It is governed by multiple processes such as genomic instability, telomere attrition, epigenetic alterations, and mitochondrial dysfunction. These, in turn, can be influenced by many external factors like environment, toxins, radicals, lifestyle and diet. Epigenetics can be described as the software which regulates the expression of gene sequences seen as hardware. This plays an important role in the continuing process of aging.
Telomeres are protective structures at the ends of our chromosomes that get shorter with each cell division. Once the telomeres become critically short, the cell ceases to divide and becomes senescent or undergoes apoptosis and dies off. Inflammation caused by metabolic diseases such as obesity, by immune responses or DNA instability caused by epigenetic dysfunction contributes to mechanisms of premature aging. Increased experience in genetics, epigenetics, and metagenomics has driven healthcare towards individualized health solutions.

The Hallmarks of Aging: A Short Overview

In recent years, scientists studying the molecular and cellular processes that govern these changes and their variation in individuals have identified nine interconnected “hallmarks of aging”. Determined mainly by our genetics but modulated by environmental factors, each of these nine hallmarks contributes to the damage that occurs with age and ultimately drives age-associated pathologies, such as Alzheimer’s disease and cancer. The following hallmarks of aging are described thoroughly in the published scientific paper which you can find via the link below.

Telomeres

Our chromosomes have protective capping structures called telomeres. These caps are shortened with each cell division are therefore markers of our biological age. The shortened telomeres can no longer protect genomic information, and this can lead to the development of various diseases such as cancer. Hence, telomeres are important regulators of cellular health and aging. Besides the internal mechanisms regulating telomere length, nutrition and lifestyle can also influence telomeres. For example, plant ingredients (especially polyphenols from green tea) and sufficient physical activity have shown a positive effect on telomere length. On the other hand, research shows that alcohol and smoking can have a negative effect.

Oxidative Stress and DNA Damage

Reactive oxygen species when overabundant lead to oxidative stress that can originate from the organism as well as from external sources such as overexposure to UV-radiation, smoking, or excessively charred meat. These reactive oxygen species or free radicals can further damage macromolecules in the cell, especially the DNA which can break. There are approximately 800 incidents of DNA damage in our bodies per hour. That is, 19 000 hits to our DNA every day.

If not repaired, this can lead to mutations and then to diseases such as cancer and premature aging. Consequently, a proper function of DNA repair is essential and strongly influenced by what we eat.
Therefore, it is important to reduce oxidative stress through a diverse diet consisting of a high level of antioxidants, such as EGCG from green tea, garlic, or omega-3 fatty acids. Alternatively, the consumption of supplements containing high doses of antioxidants such as Timeblock is recommended.

DNA Health and Lifestyle

Epigenetics: Fundamentals

Epigenetics refers to changes in the expression of genes but does not actually alter the genetic code itself. At least three systems including DNA methylation, histone modification, and non-coding RNA (ncRNA)-associated gene silencing are currently considered to initiate and sustain epigenetic changes. These epigenetic marks (like methyl groups from folate metabolism and acetyl groups) sit on top of your DNA and turn genes on and off. When a gene is turned on, it is active and is performing a certain function (expressing). When a gene is turned off, it is not active and not performing a certain function. It is almost as if the gene is not there.
Epigenetic changes are regular and natural occurrences, but they can also be influenced by several factors including age, the environment/lifestyle, and disease. For example, the type of food we eat and how much, micronutrient intake, the time of day, how much sleep you get, stress, and exercise all regulate changes in epigenetic factors and, thus, gene expression. In addition, these epigenetic marks can be passed on to your children and grandchildren through the germline (i.e. egg and sperm cells). Researchers have shown that when a male mouse is fed a poor diet, this not only affects him but also his offspring.

The Epigenetic Signature of Aging

Based on the methylation patterns of the blood cells, research is now able to identify the biological or cell age of an individual. There are specific signals that occur with age which change epigenetic marks. Particularly, the methylation status near certain genes involved in DNA repair increases with age, thus turning them off. If these DNA repair genes cannot function properly, the DNA damages lead to mutations that can subsequently results in cancer. This changes can also arise near genes important for stem cell function, metabolism, antioxidant function, stress resistance, and moreover, near genes involved in age-related diseases (such as Alzheimer’s disease and cancer).

Nutrition & the Epigenome

Detoxification, antiinflammatory agents, radical scavengers, antioxidants, antihormonal effects, cell growth inhibition, programmed cell death – all these are terms that have been connected with the prevention of premature aging and age-related diseases by nutritional factors. Epigenetic mechanisms play a pivotal role in enabling the organism to adapt to changes in the environment. Disruptions to these processes contribute to aging and the genesis of (chronic) disorders – also including carcinogenesis.

Is there anything we can do to delay or reverse these changes that occur with age?

Phytonutrients

The nutrients we extract from food enter metabolic pathways where they are manipulated, modified, and moulded into molecules that our bodies can use. A number of bioactive dietary components with antioxidative impact have a potential to prevent diseases and promote overall health.

Fruits and vegetables are not just vehicles for antioxidants; they contain innumerable phytonutrients that can boost our detoxification enzymes, modulate gene expression, and even repair DNA. Important representatives are: green tea polyphenols (especially EGCG), the soy metabolite (Equol), as well as sulphoraphane from broccoli and resveratrol (known as component of red wine). Epigenetic modifications induced by these compounds can bring multiple benefits. They can turn off genes that are known to cause cancer and can also turn on genes, helping to repair our DNA and fight cancer.

The unique Timeblock preparation is also rich in valuable active ingredients such as EGCG and folate and therefore a continuous intake has advantageous health effect.

Intermitted Fasting and Caloric Restriction

Besides the bioactive components of nutrition, fasting or caloric restriction is expected to have an impact on prevention of cancer as indicated by the findings of several studies. Periodic fasting can be as powerful as toxic chemotherapy in the treatment of some cancers in mice. Limited food has been shown to extend the lifespan of yeast, worms, flies, dogs, and monkeys, suggesting this is an evolutionarily conserved trait. There are two paradigms: one includes eating ~30% less food than you would normally eat (which is called caloric restriction) and the other involves alternate day fasting (which is called intermittent fasting).

Many studies have consistently found that decreasing food intake increases the expression of genes involved in dealing with stress including the repair of damaged DNA, proteins, and cells. All genes that decrease with age and have been shown to be epigenetically regulated with age are increased with caloric restriction and intermittent fasting.

Inflammation caused by metabolic diseases such as obesity, immune responses, or DNA instability caused by epigenetic dysfunction contributes to mechanisms of premature aging.

A compilation of epigenetic influences on humans:

Skin health

Research recognizes that skin aging is influenced 60% by genes and 40% by lifestyle. Everything you eat becomes a part of not only your inner being but the outer fabric of your body as well. The healthier the food is that you consume, the better your skin will look. Any number of chronic skin problems can be directly linked to diet. Epigenetic modulations of key genes responsible for skin aging (including antioxidant protection, collagen breakdown, and telomere length) have a huge impact on how your skin ages and consequently its shape. Drinking water is one of the best things you can do to keep your skin in shape. It keeps your skin moist. Another very important factor for a healthy skin diet is a sufficient vitamin A supply, for example from dairy products.

Skin and its Microbiota

Human skin is a 1.8 square meter diverse habitat and hosts around 1 billion microbes per square centimeter. It is a complex ecosystem of transient or resident, beneficial, mutualistic, or pathogenic members like bacteria, fungi, viruses, mites, and archaea. The resident skin ecosystem varies highly intrapersonally and interpersonally, depending on its location on the body. It is controlled by moisture, temperature, one’s gender, age, and genetics as well as individual environmental factors. The skin ecosystems, called microbiota (MB), of people with decreased immunity are weakened, permitting colonization of opportunistic pathogens. Changes in the skin caused by microbial communities are associated with many health conditions.

The superficial layers of the skin are naturally acidic (pH 4-4.5) due to acids produced by skin bacteria. At this pH value, mutualistic bacteria such as Staphylococci, Micrococci, Corynebacterium, and Propionibacterium grow. Transient bacteria do not grow, however, such as Escherichia and Pseudomonas or Staphylococcus aureus. It has been observed that the skin swells under alkaline conditions and consequently opens up.

Skin microbiota

Skin microbiota

Skin Microbiota and Aging

The skin microbiome has been shown to protect against pathogen bacteria. It can eliminate toxins and free radicals which can damage the skin and cause early signs of aging. Skin microbiota can also repair the harmful damage caused by free radicals. Probiotics have been proven to strengthen the skin’s barrier function and help the skin to uphold moisture. Well-hydrated skin makes wrinkles less visible. Skin cream containing Streptococcus thermophiles was reported to increase moisture in the skin of aging women. Evidence shows that probiotics can help protect skin against damaging UV rays which cause premature skin aging and wrinkles.

Skin microbiota and generation of body odor

Sweat is odorless until bacteria metabolize it and create by-products. The ‘wrong’ bacteria can transform sweat secretions into volatile malodorous compounds (Propionibacteria can turn amino acids into propionic acid; Staphylococcus can transform sweat into isovaleric acid (3-methyl butanoic acid); Bacillus subtilis creates strong foot odor). The presence of Staphylococcus epidermidis spp. in the axillary region is reported to result in a better axillary odor. Corynebacterium spp. was identified as the main malodor producer. Skin microbiota transplantation has been described to improvement odor on short (one month – 90%) and longer term (three months or longer – 50%).

Reestablish your skin microbiome with:
– Individualized prebiotics and/or probiotics for beauty products
– Individualized probiotics for youth preservation
– Individualized prebiotics and/or probiotics for deodorants or odor changing products

Gut health

Gut microbiota are known as the sum of all microorganisms in the digestive tract, including bacteria, fungi, and archaea. Today microbiota are estimated to contain up to 100 billion microorganisms corresponding to a volume of 1 to 1.5 kg. There are more than 3 million microbial genes in our gut microbiota –150 times more genes than in the human genome.

For the health of the entire body, it is very important that the various types of bacteria are in a balanced relationship with each other. While under normal conditions the microbiota are more or less consistent, the overall interaction of bacteria in the intestines can be disturbed by antibiotics, infectious diseases, severe mental stress, or poor nutrition. They produce short chain fatty acids, which on one hand serve as food for the intestinal mucosa, but also act as an anti-inflammatory, and according to studies, they are intended to protect against colon cancer. Short chain fatty acids are also highly involved in the regulation of hunger and satiety in the brain. Scientific evidence regarding the impact of metabolites on the psyche and the mental state are also undisputed. 99% of the intestinal flora consists of four strains of bacteria: Firmicutes, Bacteroidetes, Actinobacteria and Proteobacteria. One third of our gut microbiota is common to most people, while two-thirds are specific to each one of us. In other words, the microbiota in your intestine is like an individual identity card.

Diet and Gut Microbiota

The food we eat plays an essential role in maintaining the diversity and proper function of our gut microbiota. “We are what we eat” as what we consume also feeds off the bacteria living in our digestive system. For this reason, a varied and balanced diet is essential. Prebiotics, sometimes called fermentable fibre, are naturally present in vegetables and fruit such as garlic, onions, leeks, asparagus, artichokes, tomatoes, bananas, plums, and apples; as well as in grains and cereals like bran, and in nuts like almonds. For this reason, vegetables, fruits, and cereals should be part of a balanced and healthy diet. There is a strong hypothesis linking the mechanisms of gut microbiota, lipid metabolism and vascular diseases.

Bildquelle: Singh RK, Chang HW, Yan D, et al. Influence of diet on the gut microbiome and implications for human health. J Transl Med. 2017; 15(1):73. doi: 10.1186/s12967-017-1175-y.

Bildquelle: Singh RK, Chang HW, Yan D, et al. Influence of diet on the gut microbiome and implications for human health. J Transl Med. 2017; 15(1):73. doi: 10.1186/s12967-017-1175-y.

The discovery of intestinal microbiota and their role on the control of metabolic diseases allows for numerous therapeutic strategies such as prebiotics, probiotics, and immune modulation. It also allows the generation of biomarker strategies to set predictive profiles, to classify, and to stratify the patients and the corresponding metabolic and cardiovascular diseases.

Bildquelle: https://www.researchgate.net/figure/51688399_fig2_The-inflammatory-burn-gut-microbiota-dysbiosis-and-the-origin-of-metabolic-impairments

Bildquelle: https://www.researchgate.net/figure/51688399_fig2_The-inflammatory-burn-gut-microbiota-dysbiosis-and-the-origin-of-metabolic-impairments

A better knowledge of the properties of our microbiota composition could contribute to the improvement of individual medical care or allow a determination of the ideal personal diet. This offers the possibility to determine in advance who will benefit from which diet or which drug and who will not be able to respond.

Our Analytical Concept:

Increased knowledge in genetics, epigenetics, microbiota, and molecular mechanisms has resulted in the possibility of analytical concepts for an individualized healthcare. Popularity of genome-based testing methods for certain diseases grew in recent years, yet they are controversially discussed by experts for their lack of consideration for epigenetic or environmental factors. Our analysis aims to establish a preventive concept in cooperation between the client and a health professional. With our analytical concepts, we try to identify causal mechanisms of health issues. This approach will strengthen intervention and monitoring. We integrate lifestyle, nutrition, and molecular analysis to give you an individualized optimal intervention plan for delaying premature aging and to promote healthy aging. Analysis in this area has to be guided by a responsible medical expert.