DNA damage in human skin and the capacities of natural compounds to modulate the bystander signalling

Human skin is a stratified organ frequently exposed to sun-generated ultraviolet radiation (UVR), which is considered one of the major factors responsible for DNA damage. Such damage can be direct, through interactions of DNA with UV photons, or indirect, mainly through enhanced production of reactive oxygen species that introduce oxidative changes to the DNA. Oxidative stress and DNA damage also associate with profound changes at the cellular and molecular level involving several cell cycle and signal transduction factors responsible for DNA repair or irreversible changes linked to ageing. Crucially, some of these factors constitute part of the signalling known for the induction of biological changes in non-irradiated, neighbouring cells and defined as the bystander effect. Network interactions with a number of natural compounds, based on their known activity towards these biomarkers in the skin, reveal the capacity to inhibit both the bystander signalling and cell cycle/DNA damage molecules while increasing expression of the anti-oxidant enzymes. Based on this information, we discuss the likely polypharmacology applications of the natural compounds and next-generation screening technologies in improving the anti-oxidant and DNA repair capacities of the skin.