It was only in 1965 that scientists found out that human genes work in exactly the same way as those genes found in bacteria. To allow an organism to exist countless substances have to be constantly produced, and the genes control which substance is produced and when. It is only a small step from this finding through to intervention in this process – genetic engineering. Discussions have been going on for more than 40 years, particularly since human genetic material was completely decoded in 2001. We are now able to read the book of life; though we are still unable to understand it.
Genes in the human body
The human body consists of around 100 billion cells. Almost all of these cells contain the complete human genetic material, with some 23,000 genes. Chromosomes contain a long string of DNA, packed by means of protein molecules where the genes are localised. One somatic cell contains 23 pairs of chromosomes. One gene normally controls the formation of one or more protein inside the cell. There are also genes that activate other genes thus acting in a rather indirect way. In doing so, all of them contribute to the development of characteristics such as the colour of the skin, the hair and the eyes. But genes also determine a human's lifespan. Today, scientists are feverishly searching for exactly those genes that program natural cell death and all the mechanisms involved in that process. If it was possible to modify those genes, a prolonged life would be within our reach. Such genes encode the factors that are responsible for a fruit fly living for three months while a tortoise can live for up to 150 years.
Is it possible to turn back the biological clock? The human body starts to catabolise tissue and cells beginning in the mid-twenties. Recent research shows that vitamin A and carotenoids reactivate the metabolism of the skin while B vitamins regulate the water content, and vitamins C and E are responsible for regeneration of the skin.
More than one million cells of the aforementioned 23 billion cells in the human body die a programmed cell death daily. This serves mainly to make room for younger, healthier cells, e.g. following the massive cell death when a person suffers severe sunburn. The genetic material of the cells harmed by UV radiation must be prevented from coming into general circulation in the body, thus minimising the risk of developing cancer. Several messengers (so-called ‘Messengers of Death’) have been identified which – once they are set free – drive cells to suicide: the genetic material inside the cell core decomposes and the cell dies.
However, the older humans become the less often old cells are replaced by new ones. This means that from the age of 40 onwards the skin gets thinner by one per cent every year. The proteins collagen and elastin, which are responsible for the skin's elasticity, are reduced by two per cent every year. The reason for this is that errors creep into the complex process of metabolism. It is chiefly the cells' ‘power stations’ that tend to wear out and mutate, thus accelerating skin ageing. Experiments carried out with the aim of protecting the mitochondria using certain substances have failed because of the complexity of the problem.
Genetic engineering
Over the past few years genetic engineering has been quite successful: a fish gene has been used to make strawberries chill resistant, it has been possible to increase the muscle mass in mice, to make maize resistant to herbicides etc. However, as far as the growth and regeneration of the skin are concerned, scientists have not yet been so fortunate.
A cosmetic that is able to influence the genetic mechanisms is still a far off dream, as is gene therapy in many diseases. When you consider how complex the individual steps of the control mechanism of the skin and the connective tissue are, you can imagine how much time it would take for decisive progress to be achieved in this field.
Mass market products offered under the name DNAge try to persuade customers by saying that the ingredient folic acid will influence the genetic control of the skin cells. The assertions that the cell-active folic acid strengthens the DNA directly inside the cell core, that it protects the DNA against external influences and that it improves the healthy process of cell regeneration is not supported by scientific fact. Such assertions are therefore nothing but marketing ploys!
Another area that has so far been investigated only to a small degree is the impact of so-called signal molecules on the genetic mechanisms of the body. In humans, insulin is an example of such a signal molecule potentially coordinating the reaction to stress throughout the body. Other molecules of this type have only undergone rudimentary study. In mice and rats, key proteins such as p53, FoxO and Ku70 can cause cell death or activate cell repair. In this context it is interesting to look at the sirtuin group inside mammalian cells. These are enzymes that control cell metabolism in several ways. For example, the Sirt-1-enzyme controls the following target proteins.
1. FoxO1, Fox=3 and Fox04: transcription factors for genes involved in cell protection and glucose metabolism.
2. Histones H3, H4 and H1: control the packing density of the DANN inside the chromosomes.
3. Ku70: transcription factor, stimulating the DANN repair and cell survival.
4. MyoD: transcription factor, stimulating the development of muscles and the repair of tissue.
5. NcoR: regulator, influencing numerous genes including those involved in lipometabolism, in inflammation processes and in the functions of other regulators such as the PGC-1? protein.
6. P300: regulator, responsible for the adherence of acetyl groups to histones.
7. p53: transcription factor, initiating the programmed death of affected cells.
8. PGC-1?: regulator, controlling the cell respiration and apparently playing a decisive part in the development of muscles.
9. NF-?B: transcription factor, controlling inflammations and the survival and the growth of cells.
Human connective tissue cells – fibroblasts – were found to be controlled by at least 337 genes; they behave in very different ways depending on the anatomic region in which they originate. In addition, dieticians today are convinced that everything we introduce into our organism influences the efficacy of the genes.
The single nutrition molecules are washed as tiny molecules through the body just like driftwood. They reach the cells and supply them with energy. Part of everything we eat arrives in these power plants in our organisms. The nutrition molecules are thoroughly checked at the cell membrane before they can enter the cell. Occasionally, however, toxins (e.g. alcohol) may avoid the controls and damage the cells dramatically. On the other hand, vitamin C from orange juice can stimulate genes inside cells to generate collagen. In one part of the cell – the endoplasmic reticulum – the new fibre takes shape. The cell core conserves the most precious treasure – the DNA. Access here is only possible for substances having a special permit: proteins and nutrition substances activating the genes. Of course toxic substances may cause damage here too.
The investigation of the interplay between food and genes has only just begun. Maybe genes can be switched on and off, decelerated or accelerated through certain diseases. Expectations are high in this area.
Summary
These examples are just to show how complicated these problems are in detail. Research in this area is going on in numerous laboratories worldwide. Methods on a molecular level such as DNA microarrays are continuously becoming more accurate and more effective. The results might assume great importance, especially for the development of cosmetic preparations, in a few years time. If it is then possible to cause fundamental changes to the skin and the connective tissue of the skin using signal molecules, we will have made a great step forward. Today, unfortunately, this is still nothing but a dream.
References
1. Der Mensch und seine Gene, GEOkompakt Nr. 7, Verlag Gruner + Jahr, Hamburg, 2006.
2. Welt der Wunder, Heft 09-2006, Heinrich Bauer Verlag, Hamburg, 2006.
3. Gene für ein langes Leben, Spektrum der Wissenschaft Verlagsgesellschaft mbH, Heidelberg, October 2006.
4. R. Holtz and W. Vitz, DANN Microarray: application to personal health care and cosmetic industries. Cosmet. Sci. Tech., 2006.
5. J.L. Rinn et al, Anatomic demarcation by positional variation in fibroblast gene expression programs. PLoS Genetics, 2006, 2(7), 1084-1096.
6. A. Olaharski et al, The flavoring agent dihydrocoumarin reverses epigenetic silencing and inhibits sirtuin deacetylases. PLos Genetics, 2005, 1(6), 689-694.
7. C. Bonilla, The 8818G allele of the agouti signaling protein (ASIP) gene is ancestral and is associated with darker skin color in African Americans. Hum. Genet., 2005, 116(5), 402-406.
8. A.J. Ammermann et al, Comment on Ancient DNA from the first European farmers in 7500-year-old Neolithic sites. Science, 2006, 312(5782), 1875.
9. K.A. Beaumont et al, Altered cell surface expression of human MC1R variant receptor alleles associated with red hair and skin cancer risk. Hum. Mol. Genet., 2005, 14(15), 2145-54.