Page 86 - Read Online

Mataix et al. Plast Aesthet Res 2020;7:69 I http://dx.doi.org/10.20517/2347-9264.2020.138 Page 3 of 16

Figure 1. Damaging activity of external aggressive factors (exposome). Current knowledge (primarily from in vitro/ex vivo studies) of
®
cell/tissue damage mechanisms, their counteracting defense pathways, and how they are affected by Edafence are summarized
compounds such as hydrocarbon molecules, and particulate matter, either coarse or fine (usually termed
PM and PM according to their size in microns). All these compounds have been shown experimentally
2.5
10
to induce damage and stress responses in skin cells and tissues and correlate with aging (in fact, they are
precursory to a major share of differences in skin aging between urban and rural areas ), but their net
[9]
effect must also take into account synergistic effects among each other, as well as with radiations (see
below) [10,11] . Their molecular action mechanism is varied, but most of these agents induce oxidative stress
and damage of cell structures [for example, nitric oxide (NO) and O can promote lipid peroxidation [5,12] ]
3
and activate adaptive responses primarily aimed at reducing cell damage, which in the long term contribute
to the aging phenotype [most prominently, the aryl hydrocarbon receptor (AhR), see below].

Tobacco
It may be considered “portable pollution”, as it constitutes an efficient means to deliver more than 2000
harmful substances to our organism and skin, including CO, formaldehyde, hydrocarbons, different
toxic elements (cadmium and mercury), and tar, and, together with the characteristic effects of gestural
wrinkling and skin pigmentation, its dismal impact on skin aging is well-established [5,13] . Tobacco smoke
induces generic oxidative stress (partly due to its impact on mitochondrial function) and DNA damage,
and, importantly, it has been shown to impair activated motility and alignment of fibroblasts and wound
healing. It also induces stress hallmarks of connective tissue remodeling [matrix metalloprotease 1 (MMP1)]
and compromises skin barrier integrity [5,14-16] .

Light radiation
Solar exposure is currently recognized as a prime environmental agent contributing to skin damage and
[5]
aging, and the term photoaging has been coined to specifically describe this effect . Because of their
sustained, cumulative impact throughout an individual’s lifespan and their relevance as a prime oncogenic
agent, as precursor of melanomas and other skin cancers, the impact of light radiations on skin homeostasis
has been intensively studied for a long time [17,18] . Solar radiation, and particularly its high-energy ultraviolet
radiation (UVR) spectrum, induces profuse alterations in the genomic material of skin cells, even before
transformation phenotypes become apparent . These alterations are direct precursors of tumorigenesis
[19]
and senescence [18,20,21] . Light radiations are also powerful inducers of adaptive responses that can primarily
counteract direct cell or tissue damage, but also intersect with pathways regulating immunity [5,18,20,22] ;