Epigenetic elixir of youth: What determines how old we will live and how fit we will be?

“Your parents are both in their nineties, you’ll be here by the time you’re a hundred”! You may hear similar phrases often, but their validity is limited. Although ageing is closely linked to genes, “hard heredity” is only a minor part of it. What we call epigenetic influences are far more important. Thus, we can influence our own life expectancy and, in particular, our fitness in old age to a large extent – for example, through our diet and lifestyle.

Studies on twins have shown that heredity contributes only about 20-30% to life expectancy. Thus, a much larger role is played by what we call epigenetic influences. These are lifestyle (diet, exercise, smoking…) and environmental influences that activate or deactivate individual genes in our DNA.

It is true that the rate of negative epigenetic reactions increases with age, i.e. our genes become less “functional” as we age. This is a fact that, unfortunately, we cannot change. However, we can influence the rate at which these negative epigenetic changes increase quite substantially, and we can even reverse some of the changes that have already taken place.

Key reactions for the aging process

So far, scientists have identified a number of processes at the cellular level that are related to ageing. Here are some of them:

Changes in the chromatin – DNA is not stored loosely in cells, but is “coiled” on proteins called histones and together they form a structure called chromatin. In all so-called eukaryotic cells – from yeast to humans – it is the loss and changes in chromatin structure that have been described in connection with ageing, which can result, among other things, in the silencing of genes in that region.

Production of sirtuins – due to ageing, the production of proteins called sirtuins decreases, which significantly affect the activity of a number of important genes (in mammals it is mainly the sirtuin SIRT-1). Some research suggests that changes in sirtuin production are closely related to, for example, memory decline.

Histone modification – the production of enzymes involved in reactions called histone modification decreases with age (in particular, histone acetylation and methylation). These reactions are crucial for a gene to be “read”, i.e. for proteins to be made according to it.

Gene methylation – this is the best-studied epigenetic response associated with ageing. It is a reaction in the area of the so-called gene promoters (the area where the reading of the gene starts) – if the promoter is excessively methylated, the activity of the gene decreases. Methylation is abundant at different times of life, when it silences genes that will no longer be needed in later periods. However, some of these changes have also been shown to be related to ageing. It is interesting to note that in some areas hypomethylation (i.e. reduced methylation) occurs due to ageing, while in others there is excessive methylation, i.e. hypermethylation.

Non-coding RNAs – Until now, most scientific studies have focused on so-called microRNAs – short stretches of nucleic acids that carry no genetic information but are nevertheless important players because they regulate the process of reading individual genes. However, in addition to these, long non-coding RNA chains are also important – disruption of their production is involved in a number of negative conditions, be it cancer, cardiovascular or neurodegenerative diseases, as well as in the ageing process. However, microRNAs also play a role, some of which accelerate the ageing process, while others promote longevity.

Telomere length – at the end of each chromosome is a portion of the DNA strand with a specific order of nucleotides called a telomere. This part does not carry any genetic information, but together with the proteins it surrounds, it is responsible for protecting the ends of the chromosomes. But with each cell division, the telomeres shorten, and when their length reaches a certain critical limit, the cell dies. The process of telomere shortening is therefore closely linked to ageing. A key role is played by the enzyme telomerase, which can slow down the shortening process, but its production decreases with age.

What about heredity?

As we described above, “hard inheritance” – the structure of DNA acquired from parents – accounts for only about a quarter of longevity. So how is it possible that some families are downright longevity-rich, while others die prematurely all too often?

From our parents, at conception, we receive not only their genes, but also a part of the epigenetic changes that they have accumulated during their lifetime (until conception) or inherited from their ancestors. Thus, many epigenetic changes can be passed on over many generations, including those related to longevity. In addition, the lifestyle of a particular family – dietary habits, level of physical activity, etc. – undoubtedly plays a role.

Lifestyle often decides

As mentioned above, one of the most important epigenetic factors is our lifestyle and the environment we live in. This shapes many of the epigenetic changes within our DNA, and can also reverse many of them, including inherited ones. So what can help?

Nutrition is very important. Malnutrition is dangerous, especially in childhood, when it can shorten the lifespan not only of the person concerned, but also of their grandchildren. However, overeating also has a negative effect – in our conditions, restricting calorie intake has a positive effect on life expectancy. The composition of the diet is also important – in general, excessive intake of carbohydrates and saturated fats has a negative epigenetic effect, whereas many substances contained in a plant-based diet (especially fruits and vegetables, but also olive oil) have a positive effect.

Excessive alcohol consumption and smoking have a very negative effect on ageing-related epigenetic changes, especially on gene methylation. On the other hand, regular physical activity has a positive effect.

However, the links between ageing and our psyche are also interesting. For example, research has shown that some psychiatric illnesses, particularly depression and bipolar disorder, cause epigenetic changes that accelerate the ageing process. So when people say that a cheerful mind and positive thinking are prerequisites for a long life, this may be truer than we admit.

Useful dietary supplements

In addition to lifestyle changes, epigenetic dietary supplements can also help in the quest to prolong life and improve its quality. These are usually substances that are commonly found in our diet, but in a much more concentrated form.

Resveratrol, a red wine dye, helps regulate the level of gene methylation and histone modification, while promoting the production of sirtuins, which help slow the aging process. In addition, resveratrol helps to reduce the risk of a number of age-related diseases and protects cells from oxidative damage thanks to its antioxidant action. It also has a positive effect on the signs of ageing in the skin – for example, on the formation of wrinkles. For women during and after the menopause, it is also important that resveratrol acts as a phytoestrogen and is therefore able to mitigate the negative effects of the decline in female sex hormone production.

EGCG – epigallocatechin gallate, abundantly contained in green tea, for example, can very effectively regulate the processes of gene methylation, histone acetylation and regulation by non-coding RNAs. In addition, it also helps to regulate the activity of the enzyme telomerase, thereby limiting telomere shortening in chromosomes.

Vitamin D3 – vitamin D3 deficiency is one of the causes of brain and cognitive decline in older age (including memory), but it also increases the risk of a number of age-related diseases (osteoporosis, diabetes, heart disease and cancer). In addition, the likelihood of vitamin D3 deficiency increases significantly with age.

Genistein – a substance contained mainly in soybeans combines epigenetic and estrogenic effect. This makes it particularly effective in slowing the aging process in women during and after menopause. It also reduces their risk of age-related diseases such as osteoporosis, cancer, cardiovascular disease and Alzheimer’s disease (more here: https://www.epivyziva.cz/genistein/)