The exposome is defined as the set of non-genetic factors to which we are exposed throughout our lives and which condition our state of health and disease.

The WHO estimates that approximately 25% of diseases are related to these non-genetic factors, which could be avoided. Therefore, it provides extremely valuable information in the design of preventive, diagnostic, and therapeutic strategies in the medicine of the future.

Dr. Débora Nuevo – Neolife Medical Team

What is the EXPOSOME?

The set of traits presented by each individual is what we call phenotype, which is the product of each person’s gene combination (called a genotype) within a given environment.

What we understand as an exposome, a term coined by C. Wild in 2005, is the set of environmental (non-genetic) factors to which each individual is exposed from the moment of conception and which may condition the state of health or disease.

This name encompasses multiple factors, which also vary over time, and which we may group into 3 categories or domains:

• The General External domain includes social, economic, and psychological factors, such as education, climate, psychological stress, and the social or financial situation.
• The Specific External domain includes the influence of infectious agents, chemical and environmental contaminants, radiation, alcohol and tobacco use, profession or occupation and medical treatments.
• The Internal domain refers to metabolism, circulating hormones, microbiota, inflammation, lipid peroxidation, oxidative stress, and aging.

Variability and susceptibility windows of the exposome

In order for non-genetic factors to impact our health, they need to be able to alter biology at different levels (altering the microbiota, interacting in metabolic processes, decompensated the usual cellular pathways…).

That’s why the exposome is especially difficult to cover. Not only because of the variability of its nature but also because it is modified over time, that is, it is dynamic.

Its effect depends on the dose or the level of exposure, as well as the moment in which it occurs, so we are talking about intrapersonal variability.

And this effect does not turn out to be the same in all individuals, with population groups that are more susceptible than others, also leading to interpersonal variability.

On the other hand, it is worth mentioning the existence of windows of susceptibility, which are the specific periods throughout an individual’s life in which they are especially sensitive to certain exposures. An example is the special susceptibility to many factors at early stages of life, which may condition important events in later stages.

How do we study the exposome?

Due to the complexity of the term exposome, the approach must be multidisciplinary and comprehensive.

To obtain the data for the study of the exposome, biomonitoring is the most widely used strategy. There are two types of biomonitoring, which in turn complement each other by providing a more complete picture:

• Human biomonitoring: It consists of collecting biological samples, usually blood or urine. Concentrations of toxics or pollutants and their metabolites are analyzed. Other parameters that are compared to reference values are also measured.
• Environmental biomonitoring: It collects environmental samples that may include food, water, or air, and so their presence and the level of exposure are linked to the environment of the different population groups.

The biomarkers in turn may indicate:

• Exposure, indicating only the presence of a substance,
• Effect, the evidence of biochemical, physiological, or behavioral alterations that are associated with diseases,
• Susceptibility, in relation to the ability to respond to the exposure of a non-genetic factor.

The exposome in health and disease

According to the WHO, among the top 10 causes of death linked to a person’s life environment we find cardiovascular disease, cancer, and respiratory diseases.

Cardiovascular diseases

The role of an individual’s diet on the cardiovascular system is well known. For instance, a diet rich in salt or fat may lead to high blood pressure or dyslipidemia, which in turn are risk factors for atherosclerosis, myocardial infarction, or stroke.

The microbiota is also widely related to the risk of cardiovascular disease. Certain foods and components of the gut flora have been linked to a higher risk of atherosclerosis. An example is L-Carnitine, which is found in meats or dairy products and is metabolized by the gut microbiota generating, among other compounds, N-trimethylamine oxide, which promotes cardiovascular inflammatory processes.

Pollution, noise, or lifestyle habits are also factors that may be avoided and help lower the incidence of cardiovascular disease.

Early identification of these exposure factors and their elimination are key strategies in the development of preventive plans based on each individual’s exposome.

Cancer

Cancer is a multifactorial disease, and a large number of the factors involved are still unknown. However, it seems clear that some non-genetic factors are linked to the development of cancer,

One factor typically linked to skin cancer is exposure to the sun. UV radiation is known to cause mutations in skin cell DNA.

Additionally, some substances, like pesticides, some air pollutants, toxic substances that are present in certain foods or water (e.g. arsenic), as well as others like physical activity or circadian rhythm are also closely linked to skin cancer.

Breast cancer is also influenced by the exposome. Exposure to certain substances, like dichlorodiphenyltrichloroethane (DDT), polycyclic aromatic hydrocarbons (PAH), and heavy metals during certain susceptibility windows (such as the prenatal stage, gestation, or menopause) are strongly linked to the development of this pathology.

Lung cancer has smoking as its main non-genetic risk factor. Between 80 and 90% of lung cancers occur in smokers or former smokers.

Respiratory diseases

Once again, smoking is responsible for chronic respiratory pathologies such as COPD or asthma. Moreover, exposure to cigarette smoke during the prenatal phase also increases the risk of alterations in the fetus’ lung function and the development of diseases.

Allergies and asthma are closely linked to environmental pollutants. Climate change, urban pollution, and biodiversity loss are key to the development of allergies.

Endocrine diseases

The exposome also plays an important part in the development of endocrine pathologies. Some compounds have recently been shown to act as endocrine disruptors by altering hormonal pathways. These molecular compounds have structures that are very similar to some hormones, and through these, they can impersonate them at different steps in the operating pathway.

One example of these endocrine disruptors are the phthalates used as plastics, which are found in PVC, cosmetics, or hygiene and personal care products. These high lipid compounds, once in the bloodstream, may advance to any part of the body. In testes or ovaries, they are able to alter the secretion of hormones and cause fertility problems.

Additionally, an unhealthy diet, a sedentary lifestyle, or specific environmental components may play a key role in the development of DM II.

The exposome and the aging process

Aging is a natural and physiological process,

At the molecular level, it results in genomic instability, wear and shortening of telomeres, and a series of epigenetic changes that lead to an alteration in mitochondrial function and cellular senescence.

However, we don’t all age the same way. Aging is a biologically complex process, involving genetic and environmental factors. It is the exposome that is responsible for making a difference towards healthy aging with a similar genetic component. Some non-genetic factors have been associated with the maintenance of telomeres which is a great measure in the assessment of aging.

Pollution, smoking, obesity, and poor sleep quality are known to have a negative effect on the telomere length,

And so, the study of the influence of the exposome on cellular aging may be the key to the medicine of the future and to achieving a healthy aging process.

BIBLIOGRAFÍA

(1) Rappaport SM, Barupal DK, Wishart D, Vineis P, Scalbert A. The blood exposome and its role in discovering causes of disease. Environ Health Perspect. 2014;122(8):769-774. doi:10.1289/ ehp.1308015

(2) Wild CP. The exposome: From concept to utility. Int J Epidemiol. 2012;41(1):24-32. doi:10.1093/ije/ dyr236

(3) Olea N, Casas M, Castaño A, Mendiola J, Vrijheid M. Informe Anticipando. Exposoma. Fundación Instituto Roche. 2020. institutoroche.es

(4) https://www.vidasostenible.org/que-es-el-exposoma/

The way our genetic material works is that some genes are transcribed, that is, that their information is read and used to create a protein with a particular function, and that other genes, however, are not read, are not transcribed despite being encoded in our DNA.

Whether a cell becomes a neuron, a skin cell, or a muscle cell is determined by which genes are being read in each case. DNA methylation, in fact, regulates which genes are expressed and which are not. Simply put, methylated regions silence genes, and nonmethylated regions express genes. As previously mentioned, as we age, our DNA methylation levels decrease, and we have less control over our DNA.^.

Dr. Alfonso Galán González – Neolife Medical Team

Unlike the permanent mutations in our genes, which we cannot change, we do have the ability to change this epigenome.

In this blog post, we’ll present one of the famous 9 “Hallmarks of Aging”, or factors that determine aging, which are, in fact, reversible. We’re talking about epigenetic alterations.

Epigenetics is not the easiest thing to explain, but we’ll give it a try. If we consider the word “epigenetics”, we may see it means something that is “epi” or “over” or “on top of” our genes. Something that is not written in our genes, in our DNA, but that impacts how our genes are going to work. The way our genetic material works is that some genes are transcribed, that is, that their information is read and used to create a protein with a particular function, and that other genes, however, are not read, are not transcribed despite being encoded in our DNA. Whether a cell becomes a neuron, a skin cell, or a muscle cell is determined by which genes are being read in each case, even though all these cells have the same genetic material. So, our genome is the complete list of all the genes that we can potentially read or not read, activate or not, turn ON or OFF, and what determines this? Our epigenome.

Our epigenome are a series of markers added to our DNA without modifying its sequence, but which determine exactly that, what should be expressed and what should not.

All our cells have 23 chromosomes. Chromosomes are a tangle of chromatin, formed by nucleosomes, which look like the beads of a necklace, which are in turn made up of DNA coiled around proteins called histones. This is how structural support is given to the chromosomes and they fit in the nucleus of the cell.

Epigenetic alterations consist of changes in this chromatin and may be changes in both the histones and chromatin structure, as well as the addition of methyl groups to the DNA. These alterations may be inherited by daughter cells and therefore perpetuated.

Let’s delve deeper into the issue of DNA methylation (1).

DNA methylation, in fact, regulates which genes are expressed and which are not. Methylation patterns change over time. Simply put, though it’s actually a bit more complicated, methylated regions silence genes, and nonmethylated regions express genes. As previously mentioned, as we age, our DNA methylation levels decrease, and we have less control over our DNA (3).

This influences the function of the cells, harming them and predisposing them to the appearance of a pathology. Yes, indeed, we’re talking about the often mentioned diseases associated with aging. We now know that these epigenetic alterations, namely this change in DNA methylation patterns predispose to cancer, neurodegenerative diseases, obesity, diabetes, insulin resistance, inflammation, cardiovascular disease, immune disorders, etc. (2). These epigenetic alterations accumulate as we age, and we can measure them. Multiple “epigenetic clocks” such as Horvath’s and more complete current ones have been designed, which are used to measure just how methylated a series of genes are, giving us an idea of our biological age as opposed to our chronological age. Tests are now available that measure the methylation of millions of sites in the genome when initially only a few hundred (4) were available.

Unlike the permanent mutations in our genes, which we cannot change, we can modify this epigenome, and there are multiple studies that show how we can make these clocks start working backwards and rejuvenate our biological age, based on what they measure.

How can we do this?

Well, you’ve probably heard all this before: exercise, a balanced diet, and supplementation.

A systematic review of the scientific literature published in January this year shows us that strength training in humans induces epigenetic alterations in pathways associated with energy metabolism and insulin sensitivity, contributing to skeletal muscle health. Aerobic exercise also causes modifications in biomarkers associated with metabolic alterations through changes in specific DNA methylation and mRNA expression. It seems that the best strategy is a combination of both types of exercise (6).

Calorie restriction, which we’ve already discussed in previous blog posts, prevents a decrease in DNA methylation levels, even in different organs (5).

Calorie restriction mimetics, like metformin or resveratrol have also demonstrated these benefits.

Smoking and psychological trauma lead to changes in methylation patterns.

The availability of methyl group donor molecules influences our methylation levels. Betaine (trimethyl glycine –TMG-) is a safe supplement that helps us with this task (7). Additionally, it lowers homocysteine levels; you may see why this is important here.

In short, a decrease in DNA methylation leads to pathology and aging. This process may be reversed through exercise, a proper diet, and supplements like TMG.

We cannot emphasize enough how important it is to exercise and maintain a good diet. This is just more scientific proof of their incredible benefits.

BIBLIOGRAPHY

(1) Moore LD, Le T, Fan G. DNA methylation and its basic function. Neuropsychopharmacology. 2013 Jan;38(1):23-38. doi: 10.1038/npp.2012.112. Epub 2012 Jul 11. PMID: 22781841; PMCID: PMC3521964.

(2) Sallustio F, Gesualdo L, Gallone A. New findings showing how DNA methylation influences diseases. World J Biol Chem. 2019 Jan 7;10(1):1-6. doi: 10.4331/wjbc.v10.i1.1. PMID: 30622680; PMCID: PMC6314879.

(3) Heyn H, Li N, Ferreira HJ, Moran S, Pisano DG, Gomez A, Diez J, Sanchez-Mut JV, Setien F, Carmona FJ, Puca AA, Sayols S, Pujana MA, Serra-Musach J, Iglesias-Platas I, Formiga F, Fernandez AF, Fraga MF, Heath SC, Valencia A, Gut IG, Wang J, Esteller M. Distinct DNA methylomes of newborns and centenarians. Proc Natl Acad Sci U S A. 2012 Jun 26;109(26):10522-7. doi: 10.1073/pnas.1120658109. Epub 2012 Jun 11. PMID: 22689993; PMCID: PMC3387108.

(4) Bell CG, Lowe R, Adams PD, Baccarelli AA, Beck S, Bell JT, Christensen BC, Gladyshev VN, Heijmans BT, Horvath S, Ideker T, Issa JJ, Kelsey KT, Marioni RE, Reik W, Relton CL, Schalkwyk LC, Teschendorff AE, Wagner W, Zhang K, Rakyan VK. DNA methylation aging clocks: challenges and recommendations. Genome Biol. 2019 Nov 25;20(1):249. doi: 10.1186/s13059-019-1824-y. PMID: 31767039; PMCID: PMC6876109.

(5) Gensous N, Franceschi C, Santoro A, Milazzo M, Garagnani P, Bacalini MG. The Impact of Caloric Restriction on the Epigenetic Signatures of Aging. Int J Mol Sci. 2019 Apr 24;20(8):2022. doi: 10.3390/ijms20082022. PMID: 31022953; PMCID: PMC6515465.

(6) Barrón-Cabrera E, Ramos-Lopez O, González-Becerra K, Riezu-Boj JI, Milagro FI, Martínez-López E, Martínez JA. Epigenetic Modifications as Outcomes of Exercise Interventions Related to Specific Metabolic Alterations: A Systematic Review.

Lifestyle Genom. 2019;12(1-6):25-44. doi: 10.1159/000503289. Epub 2019 Sep 23. PMID: 31546245; PMCID: PMC6921698.

(7) Zhao G, He F, Wu C, Li P, Li N, Deng J, Zhu G, Ren W, Peng Y. Betaine in Inflammation: Mechanistic Aspects and Applications. Front Immunol. 2018 May 24;9:1070. doi: 10.3389/fimmu.2018.01070. PMID: 29881379; PMCID: PMC5976740.

The disease created by the novel coronavirus, COVID-19, as it’s widely known, presents a potentially very severe disease, accounting for over one million deaths around the world and, officially, over 34,000 deaths in Spain.

Currently, efforts are focused on preventing spreading, the treatment of the sick at hospitals, and the search for an effective vaccine. However, at Neolife we believe that they are often ignoring the state of those who have overcome the disease.

Neolife Medical Team

The concerning after-effects of COVID-19

Multiple scientific studies describe numerous and different after´-effects pursuant to the infection, even if we had a very light case:

• In a study developed in the United Kingdom, 10% of people had persistent symptoms after a positive test result.
• A study from the USA stated that 2-3 weeks after a positive test result, just 65% of people had recovered their state of health before infection.
• A German study speaks of post-COVID heart affectation in 78% of the patients under study, regardless of the severity of their initial disease, while another US study lowered this figure to 46%.

Symptoms of post-acute COVID-19 change extensively, but even in minor cases, they can be associated to different long-term symptoms.

The most common persistent symptoms are  cough, low-grade fever, and fatigue. To a lesser degree; shortness of breath, chest pain, headaches, neurocognitve difficulties, muscle and joint pain, weakness, bowel discomfort, skin breakouts, metabolic alterations such as poor diabetes or cholesterol control, thromboembolic diseases, depression, and other mental diseases, etc.

These facts, which are very disturbing, are even more so if we take into account that Spain is about to reach 1 million positive cases.

Neolife’s new post-COVID treatments

In our opinion, neither the public nor private systems have implemented the specific care to address this problem, which will cause greater morbidity and mortality associated to the virus and which will never be included in official figures.

This is what Neolife is offering services to the population aimed at evaluation patients who have overcome the disease from a deep knowledge of the possible after-effects. These post-COVID treatments include all necessary medical and analytical tests, and a thorough and specialized assessment and follow-up, if necessary.

We also address other key factors in post-COVID recovery:

• Nutrition: diet advice to address heal problems after the diseases: persistent inflammation, caloric-protein malnutrition and sarcopenia, liver detoxification, lipid an glycemic control…
• Respiratory rehabilitation (in case of persistent dyspnea), neurological rehabilitation (in those with neurological involvement) and/or joint rehabilitation (in case of muscle loss).
• Exercise prescription, providing training routines of increasing intensity depending on the medical indications and the patients’ evolution.

At Neolife – after nearly 10 years of experience in our Madrid and Marbella centers in the development of anti-aging preventative medicine, with great success – we have set a goal for patients to resume their work, social and family lives, and sport activities in optimal health.

If you wish to receive more information on Neolife’s post-COVID treatments or book an appointment with our medical team, you may call us on +34 91 732 59 50 or email us at info@neolifeclinic.com.

The negative effects of excess activation of the mTOR pathway can lead to cancer, insulin resistance, diabetes, Alzheimer’s, etc. Meanwhile, if we always keep it inhibited, we would affect the creation of tissue, muscle, bone, and cell repair – leading to sarcopenia, osteoporosis, weakness… and these are the problems of an over-activation of the AMPk pathway.

In this second part of the articles dedicated to the AMPk and mTOR metabolic pathways, we will try to give some ideas on how to balance these two pathways to get the best out of each of them. At Neolife, we know how to help you with these strategies adapted to your situation and your state of health so that you have an optimal quality of life and state of health.

Dr. Alfonso Galán González – Neolife Medical Team

High-intensity exercise, or exercise at high-intensity intervals, such as HIIT, has been shown to activate the AMPk pathway, while strength (weight) training activates the mTOR pathway.

In this second part of the articles dedicated to the AMPk and mTOR metabolic pathways, we will try to give some ideas on how to balance these two pathways to get the best out of each one.

Scientific interest in them has been increasing in recent years, as shown by the number of articles published in Pubmed when you search for mTOR:

And for AMPk:

We mentioned in the previous article that the negative effects of excess activation of the mTOR pathway can lead to cancer, insulin resistance, diabetes, Alzheimer’s, Parkinson’s, etc. Meanwhile, if we always keep it inhibited, we would affect the creation of tissue, muscle, bone, and cell repair – leading to sarcopenia, osteoporosis, weakness… and these are the problems of an over-activation of the AMPk pathway – mTOR’s “antagonistic” pathway.

Thus, we do not want to develop diabetes, neurodegenerative and cardiovascular diseases, or cancer; however, we also do not want to lose bone mass or muscle mass, which we need in order to have an adequate metabolic rate to promote the burning of fat and glucose.

Life in industrialized society almost inevitably leads us to an excess of mTOR activation, as we have plenty of food, we can eat as many times a day as we want (always maintaining high sugar levels with the consequent release of insulin), and we have sedentary jobs not needing to undertake physical activity to get our food. As we have seen, these are the things that inhibit AMPk pathway activation and that may be the cause of the increase in metabolic diseases in recent decades. Obviously, if we think about how the first humans lived, we can see that inevitably there was an alternation between exercise and rest, between eating and fasting…

Currently, we could say that we have to “simulate” all of that in order to improve our state of health and get the benefits of both metabolic pathways while avoiding the negative effects at the same time.

I hope I have been able to convey that neither of the pathways is good or bad; it is a balance between the two that will lead us to greater longevity, a life free of disease, to avoid the loss of muscle mass and bone mass, etc.

How do we balance both pathways?

Alluding to the 4 fundamental pillars of treatment of Age Management Medicine and of Neolife (which we can expand to many more, but for educational and practical purposes we will reduce to 4) which are nutrition, exercise, supplementation, and hormonal balance, we will briefly explain what can be done.

• Nutritional strategies:

The intermittent fasting that we hear about everywhere and about which we have written on our blog on other occasions is a simple technique that will activate the AMPk pathway. We recommend fasts of at least 12h to bring about activation (usual and moderately bearable strategies go up to 14-16h). From that time, the glycogen of the liver already begins to mobilize itself, glucose and insulin in blood lower, and the secretion of hormones increases – such as cortisol, adrenaline, noradrenaline, growth hormone,– as well as the biogenesis of more mitochondria to optimize energy gathering and production.

Meals should preferably be low in carbohydrates and have a low or medium glycemic index (this measures how fast and how many carbohydrates in a food get into the blood in the form of glucose). In order to activate the mTOR pathway after training, to take advantage of the conditions when the workout is over and promote muscle development, it is important for food to be rich in proteins and carbohydrates and for it to have a high glycemic load (white rice, potatoes, pasta, etc.).

• Training strategies:

As we have already mentioned, high-intensity exercise, or exercise at high-intensity intervals, such as HIIT, has been shown to activate the AMPk pathway, while strength (weight) training activates the mTOR pathway. We recommend alternating both forms of training throughout your weekly exercise routine to promote – on the one hand – carbohydrate metabolism, energy collection, fat burning, and mitochondrial biosynthesis, and – on the other – muscle development. We must stop to think here about how intimately related the two pathways are, despite their “antagonistic ” effects. As we develop more muscle, we will have more peripheral insulin receptors, which will favor AMPk action in terms of improving insulin resistance; and those muscles that are more developed because of mTOR activation will be more efficient when producing energy because they have higher mitochondrial density thanks to the activation of the AMPk pathway.

• Supplements:

There are several supplements that help us to activate these pathways in addition to the drugs already mentioned like metformin for the AMPk pathway and rapamycin for the mTOR pathway.

Alpha-lipoic acid, resveratrol, quercetin, EGCG from green tea, berberine, turmeric, anthocyanins from blueberries, zinc, carnitine, virgin olive oil, fish oil (omega 3), ginseng, cinnamon, astragalus, Coenzyme Q10, red rice yeast, and apigenin all activate the AMPk pathway.

As for activating the mTOR pathway, it is a good idea to use amino acids such as leucine, whey protein, and hydrolyzed carbohydrates, which lead to an insulin peak that activates this pathway during strength training. Testosterone also activates the mTOR pathway (Basualto-Alarcón C et al. 2013).

With this we hope to have given you a bit of a better understanding of these important metabolic pathways and how to use them to your benefit. At Neolife, we know how to help you with these strategies adapted to your situation and your state of health so that you have an optimal quality of life and state of health.

BIBLIOGRAPHY

(1) Thomson DM. The Role of AMPK in the Regulation of Skeletal Muscle Size, Hypertrophy, and Regeneration. Int J Mol Sci. 2018;19(10):3125. Published 2018 Oct 11. doi:10.3390/ijms19103125

(2) Lin SC, Hardie DG. AMPK: Sensing Glucose as well as Cellular Energy Status. Cell Metab. 2018;27(2):299‐313. doi:10.1016/j.cmet.2017.10.009

(3) Ciccarese F, Zulato E, Indraccolo S. LKB1/AMPK Pathway and Drug Response in Cancer: A Therapeutic Perspective. Oxid Med Cell Longev. 2019;2019:8730816. Published 2019 Oct 31. doi:10.1155/2019/8730816

(4) Wang Z, Wang N, Liu P, Xie X. AMPK and Cancer. Exp Suppl. 2016;107:203‐226. doi:10.1007/978-3-319-43589-3_9

(5) Saxton RA, Sabatini DM. mTOR Signaling in Growth, Metabolism, and Disease [published correction appears in Cell. 2017 Apr 6;169(2):361-371]. Cell. 2017;168(6):960‐976. doi:10.1016/j.cell.2017.02.004

(6) Bertoldo MJ, Faure M, Dupont J, Froment P. AMPK: a master energy regulator for gonadal function. Front Neurosci. 2015;9:235. Published 2015 Jul 14. doi:10.3389/fnins.2015.00235

(7) Jeon SM. Regulation and function of AMPK in physiology and diseases. Exp Mol Med. 2016;48(7):e245. Published 2016 Jul 15. doi:10.1038/emm.2016.81

(8) Xu J, Ji J, Yan XH. Cross-talk between AMPK and mTOR in regulating energy balance. Crit Rev Food Sci Nutr. 2012;52(5):373‐381. doi:10.1080/10408398.2010.500245

(9) Johnson SC, Rabinovitch PS, Kaeberlein M. mTOR is a key modulator of ageing and age-related disease. Nature. 2013;493(7432):338‐345. doi:10.1038/nature11861

(10) Kim J, Yang G, Kim Y, Kim J, Ha J. AMPK activators: mechanisms of action and physiological activities. Exp Mol Med. 2016;48(4):e224. Published 2016 Apr 1. doi:10.1038/emm.2016.16

(11) Basualto-Alarcón C, Jorquera G, Altamirano F, Jaimovich E, Estrada M. Testosterone signals through mTOR and androgen receptor to induce muscle hypertrophy. Med Sci Sports Exerc. 2013;45(9):1712‐1720. doi:10.1249/MSS.0b013e31828cf5f3

Melatonin is produced in the pineal gland, located deep in the brain and which was considered a possible receptacle for the soul in the early stages of neuroanatomy.

This molecule has been the subject of numerous studies since the 80s and, little by little, we’ve been finding out the surprising effects it has. These are not just limited to sleep, but throughout the body. We could even stretch to say that sleep improvement plays a secondary role to the rest of the benefits.

Dr. Iván Moreno – Neolife Medical Team

Now we’re going to look at the different benefits melatonin has.

This recently discovered molecule (1958), has been the subject of numerous studies since the 80s and, little by little, we’ve been finding out the surprising effects it has. These are not just limited to sleep, but throughout the body. We could even stretch to say that sleep improvement plays a secondary role to the rest of the benefits.

Melatonin is produced in the pineal gland, located deep in the brain and which was considered a possible receptacle for the soul in the early stages of neuroanatomy. There is melatonin in many species of animals and plants, which shows its basic importance in the metabolism of living beings.

High concentrations of melatonin have been found in the retina, gastrointestinal tract, bone marrow, skin and other tissues. We can therefore deduce that it may have an influence on other physiological functions through local secretion and that, far from being just a sleeping aid, melatonin has multiple effects throughout the body, including:

• Regulating the different biological clocks of the body: biological neural clocks are adjusted in cycles more or less approximate to the duration of the day (22-26 hours), but the other daily cycles of the organism such as hepatic metabolism, renal, oxidative stress, body temperature and muscle toning have less accurate clocks so they require internal synchronization. That is why when we suffer jetlag, we’re not only tired, but we feel almost sick – our body does not work properly.
• Control of oxidative stress: melatonin plays a key role in promoting the excellent health of mitochondria and an adequate control of oxidative stress.
• Prevention of dementia.
• Maintenance of the optimal neuronal state.
• Others…

The secretion of melatonin is influenced by external light through the optic nerve. This means nature allows us to synchronize with seasonal changes.

Each of us has a particular predisposition for melatonin secretion, the most frequent being the average that begins producing melatonin at around 8:00 in the evening and peaks about 2:00-3: 00 in the morning.

Quite often we find, when studying the secretion profile, a lack of coordination and insufficient secretion.

These phase imbalances and deficits in the total effect of melatonin cause the appearance of chronobiotic rhythm alterations, imbalance and oxidative stress, etc.

As we age, melatonin secretion drops in quality, resulting in imbalances of the circadian cycles and quantity thereof (figure attached).

Although the doses normally found in supplements are around 2mg, these doses are too small to reach all tissues and serve the different purposes that melatonin has. In addition, in case of using an incorrect dose we can produce the opposite effect (insomnia or de-regulation), which is why taking melatonin supplements without measuring precisely normally only goes well for some people while others report insomnia and discomfort.

At Neolife we advocate taking high doses of melatonin, which have the maximum beneficial effects, but at a personalized dose and at a specific time which will be most beneficial (and which will avoid side effects). For this reason, in collaboration with the International Institute of Melatonin, we conducted studies of melatonin profiles and oxidative stress to be able to prescribe melatonin and antioxidants properly.

Age Management Medicine Group

Recently at the annual meeting of the AMMG in Orlando, Florida, attended by part of the Neolife medical team, results from several studies were presented which showed an antineoplastic effect from high doses of melatonin. In this post we want to review some of the most important ideas that were presented:

• • There is no such thing as “high doses” of melatonin. Melatonin has been shown to be extremely safe and toxic levels of it have not yet been shown. This does not mean that we can take high doses without conducting a previous study, as even if we do not have to avoid the toxicity, we still need to pay attention to the balance of the system.
  • Exposure to blue spectrum light is the most related to the secretion of melatonin. To secrete melatonin, you do not need to sleep, you only need to be in the dark. Professor Ritter went on to say that light at night “is a drug” in relation to the harmful effects it has. This is of extreme importance as the secretion of melatonin and the preparation for an adequate night’s rest begins hours before going to bed (normally at 08:00pm). Maintaining good sleep hygiene and adapting screens to avoid blue light is essential to preserve our melatonin secretion as long as possible.
  • Melatonin and all its metabolites have a powerful effect by capturing free radicals, which are highly toxic and damage DNA, leading to degenerative, autoinflammatory and oncological diseases. It has been seen in different studies that there is a higher incidence of cancer in workers on night shift, or with alterations in the important hourly rhythms (many transoceanic journeys). In fact, light at night is included as a carcinogen by the World Health Organization.

• There is strong scientific evidence that shows that tumors appear, develop and metastasize more easily in subjects exposed to night light that prevents correct melatonin secretion.
• Melatonin inhibits many of the mechanisms that cancer cells use (Hanahan, 2011) and improves sensitivity to chemotherapy.

Following this excellent presentation and reviewing the relationship of melatonin with the appearance of tumors, specifically the breast, in greater depth we have found important scientific evidence that supports this relationship in human studies, showing a clear benefit in prevention and even by adding melatonin to the oncological treatment of breast tumors.

In an extensive review published in the journal Critical Reviews in Oncology last year, it was concluded that there is considerable evidence to support the multiple tumor suppressive effects of melatonin, showing a protective effect against chemotherapy and antitumor of melatonin, especially through its anti-gonadotropin and antiestrogenic effect on the breast tumor.

Due to its low toxicity even in high doses and the full range of benefits that it seems to have shown, melatonin can be considered as a complementary therapy to usual chemo and radiotherapy and in prevention of breast cancer in women with a history of risk or mammary fibrocystic disease.

So then, beyond the benefits for quality of sleep, melatonin is a true antiaging molecule, while allowing vital systems to continue optimum functioning and delaying the appearance of diseases – exactly what Age Management medicine and Neolife are about.

BIBLIOGRAPHY

(1) Kubatka P, Zubor P, Busselberg D, Kwon TK, Adamek M, Petrovic D, et al. Melatonin and breast cancer_ Evidences from preclinical and human studies. Critical Reviews in Oncology / Hematology. Elsevier; 2018 Jan 8;122:133–43.

(2) Majidinia M, Reiter RJ, Shakouri SK, Research IMA, 2018. The multiple functions of melatonin in regenerative medicine. Elsevier.

(3) Shirani A, JCSM ELJOCSM, 2009. Illuminating rationale and uses for light therapy. Journal of Clinical Sleep Medicine.

The Neolife Clinic, always at the forefront of anti-ageing medicine now offers this innovative melatonin cream to its clients.

As of this month, Neolife’s clients will be able to benefit from this new anti-ageing product which is the result of research conducted by Germaine Escames and Darío Acuña who are both members of the Neolife clinic’s medical advisory team.

Neolife already offers its clients two types of melatonin cream which are: MEL13 -for young skin- and MEL13 Plus – for mature skin-.

As their own creators affirm (Dr. Acuña-Castroviejo and Dr. Escames, co-directors at the International Melatonin Institute), it is not a cosmetic treatment like the ones which already exist on the market but a treatment which is designed for the sole purpose of protecting and regenerating the skin. This is where the preventive character arises, in keeping with the philosophy of the Neolife clinic, a European benchmark in preventive anti-ageing medicine.

By using this cream, which includes melatonin and coenzyme Q10, the active ingredients are able to enter the mitochondria and activate it to produce the energy required for the cell to function properly. The result includes an increase in the synthesis of proteins such as collagen and elastin, an increase in hyaluronic acid, as well as other skin components; which results in total regeneration of the skin. As such, MEL13 not only regenerates but also prevents damage caused by the ageing processing.

The benefits of the MEL13 melatonin cream include:

1. Repair and regeneration of damaged cells
2. Wrinkles visibly diminish
3. Improved hydration and strengthening of the skin
4. Anti-free radical effect
5. Recovery and maintenance of skin elasticity and smoothness
6. Intensive regeneration of the skin

There are two types of melatonin cream:

Mel13

Designed for the cellular protection and nutrition of younger skin.

Recommendation: use during the day on the face and neck after cleansing and toning. Protects the skin from environmental pollution and oxidative stress.

Mel13 Plus

For a more intensive repair and cellular rehabilitation designed for more mature skins.

Recommendation: use during the night on the face and neck after cleansing and toning. Regenerates the skin and repairs visible signs of ageing.