The natural process of development and skin aging is the process that specific sets of genes being differentially turned on/off (switched on/off) in various differentiated and undifferentiated cell types at the certain point of developmental stage. Epigenetics is the modulation of specific sets of genes in a systematic way during the developmental stages of life cycle for different phenotypes although all cells contain the same genome information. Environmental factors (extrinsic causes) either superimpose and accelerate the programmed aging process or activate distinct aging pathways to produce clinical signs of skin aging that are distinct.
Some common signal transduction pathway/mechanisms unfold genetic information during the course of developmental program at different stages of our lifetime including aging. There is common core pathways involved in the switch on and off our genes at different stages of the epigenomic unfolding of the stored genetic information. NF-κB (a transcription factor) pathway is one of them, and this pathway is implicated in our aging program too. NF-κB signalling pathways are activated by environmental stresses to turn on genes accounting for the premature aging phenotypes.
In addition, DNA methylation and histone acetylation patterns may also help to determine when and how a gene is switched on or off (known as genomic silencing or silencing gene or gene silencing theory of aging). Two chemical mechanisms account for the modulation of gene expression at the DNA level: 1) DNA methylation 2) Histone deacetylation/acetylation. Histone deacetylation is a process where DNA packaging proteins (histones) are chemically modified to adhere to the DNA more tightly, which makes it harder for genes to be active (switch off, gene silencing). The reverse process – histone-acetylation – helps activate silenced genes. The other mechanism of gene silencing is DNA methylation. When a gene’s DNA is methylated (i.e. methyl groups are attached to it), the gene becomes inactive. Conversely, the removal of methyl groups (demethylation) increases activity of genes.
Generally, histone deacetylation/acetylation is a more dynamic and more easily disrupted mechanism of gene regulation (as compared to methylation/demethylation). This may be one reason why it appears to play an particularly important role in the aging process as it can provide a mechanism for gene deregulation such as – turning on the genes that should be inactive. The enzymes responsible for histone deacetylation and thus for gene silencing have been known for some time. The most important such enzymes may be a group of proteins called sirtuins. Sirtuins are known to play a role in the aging process and life extension.