Factors of skin ageing share common mechanisms

Abstract

Ageing has been defined as the accumulation of molecular modificationswhich manifest as macroscopic clinical changes. Human skin, unique amongmammalians insofar as it is deprived of fur, is particularly sensitiveto environmental stress. Major environmental factors have beenrecognized to induce modifications of the morphological and biophysicalproperties of the skin. Metabolites from ingested or inhaled substancesdo affect skin, which is also sensitive to endogenous hormone levels.Factors as diverse as ultraviolet radiation, atmospheric pollution,wounds, infections, traumatisms, anoxya, cigarette smoke, and hormonalstatus have a role in increasing the rate of accumulation of molecularmodifications and have thus been termed 'factors of ageing'. All thesefactors share as a common feature, the capability to directly orindirectly induce one of the steps of the micro-inflammatory cycle,which includes the expression of ICAM-1 in endothelial cells. Thistriggers a process leading to the accumulation of damages in the skinresulting in skin ageing since ICAM-1 expression provokes recruitmentand diapedesis of circulating immune cells, which digest theextracellular matrix (ECM) by secreting collagenases, myeloperoxidasesand reactive oxygen species. The activation of these lytic processesprovokes random damage to resident cells, which in turn secreteprostaglandines and leukotrienes. These signaling molecules induce thedegranulation of resident mast cells which release the autacoidhistamine and the cytokine TNF-α thus activating endothelial cellslining adjacent capillaries which release P-selectin and synthesizeICAM-1. This closes a self-maintained micro-inflammatory cycle, whichresults in the accumulation of ECM damage, i.e. skin aging. In thispaper we review the evidence that two factors able to inducemacroscopical and molecular modifications in the skin, protein glycationand stretch, activate the micro-inflammatory cycle. We further presentevidence that three additional factors, two external factors(electromagnetic fields and psychological stressors) and one internalfactor (neuropeptides) also activate the micro-inflammatory cycles andmay therefore be considered as factors of skin ageing.