SIRTUIN GENES

activating sirtuins with sirtfoods:

this is how it works!

The sirtuin genes and the resulting sirtuin enzymes are activated when there is a lack of energy. Classically, this is achieved by calorie restriction (diet), fasting and exercise.

An alternative to achieve this activation, is the intake of so-called Sirtfoods. These foods contain special substances called sirtuin activators. 

active sirtuins can switch on genes that...

  • Help you to become slim and/or stay slim.

  • Increase the capacity of the anti-oxidative system and thus slow down the aging process (radical protection).

  • Maintain or improve skin elasticity.

  • Have a positive effect on the regulation of the thyroid gland, fat tissue, sugar and fat metabolism.

 

what exactly are sirtfoods?

Sirtfoods are first and foremost plant-based food items. Plants build secondary substances such as polyphenols.  These act on the sirtuins and simulate the signal of a lack of energy normally caused by fasting, dieting and exercise. 

 

This is how sirtuins become active -

WITHOUT STARVING!

 

Active sirtuins then switch on protective genes and switch off dangerous genes. 

 

Studies show that the activation of sirtuin genes can prolong life.

In countries like Japan and India, various Sirtfoods are part of the daily diet. Also known as 'blue zones', they have the lowest incidence of lifestyle associated diseases such as hypertension, obesity, diabetes, fatty liver and cancer. 

Sirtfoods are especially rich in polyphenols. The health-promoting effects of plant polyphenols are closely linked to their ability to act positively on epigenetic mechanisms and many other genes that are important for a long and healthy life.

sirtuins and their functions
th
e science behind them!

In 2003, biologist David Sinclair discovered the Sir2 gene in yeast fungi. He found that the Sir2 became active when food was scarce. Despite a lack of energy, this led to the survival of the yeasts. Furthermore, the Sir2 gene was detected in all living beings and was known as the enzyme group of sirtuins through further research. 

Humans possess a total of seven sirtuins. Sirtuins are also called SIRT (silent mating type information regulation 2 homolog). They also act as energy sensors in our cells and are activated in the same way as in the yeasts when there is a lack of energy.

Thanks to their properties, sirtuins are multifunctional and regulate many metabolic processes as well as the aging process. 

Sirtuins subcellular localization: SIRT1 is predominantly located in the nucleus, and also in the cytosol. SIRT2 is localized in the cytosol. SIRT3, SIRT4, and SIRT5 are mitochondrial proteins, but SIRT3 may also be found in the nucleus and cytosol under different cellular events. SIRT6 and SIRT7 are localized in the nucleus and nucleolus, respectively.

Sirtuins subcellular localization: SIRT1 is predominantly located in the nucleus, and also in the cytosol. SIRT2 is localized in the cytosol. SIRT3, SIRT4, and SIRT5 are mitochondrial proteins, but SIRT3 may also be found in the nucleus and cytosol under different cellular events. SIRT6 and SIRT7 are localized in the nucleus and nucleolus, respectively. [1]

The graphic shows a protein that is used by the research group headed by Prof. Dr. med. Clemens Steegborn has identified as Sirt1 substrate. It is a DNA binding protein, the DNA is orange. The deacetylation site is the single gray strand on the top right. Graphic: Prof. Dr. med. Clemens Steegborn; free for publication.

The graphic shows a protein that is used by the research group headed by Prof. Dr. med. Clemens Steegborn has identified as Sirt1 substrate. It is a DNA binding protein, the DNA is orange. The deacetylation site is the single gray strand on the top right. Graphic: Prof. Dr. med. Clemens Steegborn; free for publication.

 
 

how do sirtuins behave?

As soon as you consume fewer calories than you need, i.e. there is a lack of energy, the body is put into a kind of survival mode. This mode is controlled by the sirtuins. Cells are subjected to a substantial maintenance and repair program. Sirtuins therefore have a protective effect against age-related damage, which can lead to diseases such as diabetes, lipid metabolism disorders and cancer. 

Biochemically speaking, sirtuins are deacetylases that cleave acetyl groups from histones and other enzymes. Histones are proteins around which DNA is wrapped (see figure). In the cell nucleus, active sirtuins ensure that the DNA is packed more tightly and is no longer accessible. As a result, no copy of the genes can be made and no gene product such as an enzyme is produced. This is why genes are shut down.

 
epigenetics

 The field of epigenetics deals with the switching on and off of genes. Three epigenetic mechanisms are known to date, namely histone modifications, DNA methylation and non-coding (micro) RNAs. A superordinate machinery with which a cell regulates the activity of its genes. 

Sirtuins mainly influence histone modifications. Epigenetics forms the molecular memory for environmental influences, because natural substances from the diet act on these mechanisms and influence the regulation of gene expression (genes are read and copied). 

dna methylation

DNA methylation is the attachment of methyl groups to certain nucleotides of DNA. The DNA contains the bases adenine (A), cytosine (C), guanine (G) and thymine (T). These bases together encode the genetic fingerprint of an organism. 

A gene can be deactivated by finding methylated cytosines in its vicinity. This phenomenon prevents all genes in a tissue or cell from being copied simultaneously due to methylated cytosines acting as gene switches. In addition, special methylation patterns are formed which can be used as early markers of diseases or to determine the biological cell age.

Enzymes that attach methyl groups to the DNA, which are required for metabolism and DNA repair, are also proteins that can be activated or deactivated by sirtuins through the cleavage of acetyl groups. These enzymes play a role, for example Alzheimer's  disease,  Parkinson's disease, diabetes mellitus and obesity.

SIRTFOOD_SHOT_ENG_FINAL-4A.jpg

Schematic representation of DNA methylation and histone packaging as the main epigenetic re- gulators of gene activation. If methyl groups are added at the gene’s starting point (promoter), the gene is blocked for activation. Vice versa, if the promoter is accessible, the gene can be activated and hence, gene products like e.g. proteins can be produced. DNA is also protected from activation if the histones, around which the DNA is wrapped, are located closely next to each other. If the packaging is loosened, genes become accessible. [4]

histone modifications

Sirtuins act on the histones and split functional groups (acetyl groups). The DNA is thus packed more tightly and cannot be read, i.e. the DNA is protected.

micro rna

Micro RNAs are tiny pieces of RNA that can also immobilise genes and serve, among other things, for communication between cells and different tissues. They are important biomarkers for very current events in the body. At the same time the activity of sirtuin genes, is controlled by micro RNAs.

 

More precisely, gene copies (messenger RNA) of Sirtuin 1, for example, which are formed in the cell nucleus, can be inactivated by a special micro RNA (miR 34a). 

In concrete terms, the epigenetic regulation of DNA is disturbed by the aging process and by overweight. 

However, it is important to know that the modulation of sirtuin activity, through the intake of sirtfoods in sufficient quantity, can lead to such changes being positively influenced.

© 2019 Biogerontology Corp. All rights reserved.

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Sirt1 and binding to DNA @ Prof. Dr. Chemens Steegborn