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Burke. Plast Aesthet Res 2020;7:59 I http://dx.doi.org/10.20517/2347-9264.2020.154 Page 7 of 16

damage, particularly to the skin. The average level of O on the earth’s surface is about 0.05-0.1 ppm, quite
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low in comparison with the stratosphere with concentrations of 10 ppm. However, especially during the
summer, in densely populated cities such as Mexico City (with the highest levels) and even Rome and
Paris, industry and traffic emit VOCs including nitrogen oxides, methane, carbon monoxide, and sulfuric
compounds which accumulate, causing a progressive increase in O concentrations up to 0.8 ppm.
3

Although O cannot penetrate the skin, it oxidizes lipids on the skin’s surface, thereby triggering destructive
3
inflammatory cascades in deeper cellular layers, turning on genes to produce inflammatory cytokines
- interleukin-8 (Iℓ-8), tumor necrosis factor-alpha (TNF-α), transforming growth factor beta (TGF-β),
cyclooxygenase-2 (COX-2), intercellular adhesion molecule (ICAM), and vascular cell adhesion molecule
(VCAM) [19,20] - all of which have been measured in response to surface O . This inflammatory onslaught
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[21]
certainly disrupts dermal cells and extracellular matrix to exacerbate photoaging . Further damage
is rendered by O generation of the protein adduct 4-hydroxy-2-nonenal (HNE) and carbonyl protein
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adducts .
[22]
Direct proof that O exposure contributes substantially to accelerating extrinsic aging was demonstrated in
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Skh:1 hairless mice [22,23] . With exposure to O , dermal MMP-2 (a gelatinase that digests collagen I and IV)
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and MMP-12 (an elastase) are activated; MMP-9 (a gelatinase with activity similar to MMP-2) is activated
[23]
[24]
only in older mice . O further inhibits activation of inhibitors of MMPs , thus increasing matrix
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degradation with resultant manifestations of dermal aging: Wrinkles, crepe-like skin, and sagging due to
loss of support, seen histologically as loss of collagen with disorganization of fibrillar alignment and loss
of elastin with clumping of dysfunctional elastic tissue fragments. This degradation of firm extracellular
[25]
matrix allows and promotes enhanced tumor growth .
Defending against this damage are antioxidants vitamin C and vitamin E on the skin’s surface. However,
exposure to O rapidly depletes these essential antioxidants , probably because the resident levels of these
[26]
3
vitamins are rapidly depleted by quenching the initial onslaught of O -induced oxidative damage. Thus, the
3
first antioxidant defense is lost. Another protective mechanism is the induction of epidermal heat shock
proteins (HSP) sequentially: HSP 27 (at 2 h), HSP 70 (at 12 h), and HSP 32 (maximally at 24 h). HSP 27
actually increases 20-fold and HSP 70 by 8-fold in response to O . These HSPs may mitigate the oxidative
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harm from surface O 3 [19] . Further defending against all of the O -induced oxidative stress is activation of the
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antioxidant transcription factor nuclear factor of kappa-light-chain-enhancers of activated B-cells (NF-κB)
in keratinocytes as well as in dermal cells, as demonstrated in vitro and in vivo [19,22] .

A recently published epidemiological study from two cohort groups in Germany (of 2013 Caucasian men
[27]
and women) provides direct proof that exposure to tropospheric O does indeed exacerbate extrinsic
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skin aging. Five-year cumulative residential exposure to ambient O was calculated for each of the two
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neighborhoods (within a 5-digit postal code). Course wrinkles and hyperpigmentation (solar lentigines)
on the forehead, under eyes, crow’s feet area, and upper lip and facial lentigines were quantitated by visual
scoring according to the validated Score of Intrinsic and Extrinsic Skin Aging (SCINEXA ) . Correlation
TM [27]
of course facial wrinkles with cumulative neighborhood O exposure was confirmed, but increased
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pigmented lentigines were not noted. This correlation was independent of other possible environmental
confounders and airborne pollutants including particulate matter.

PARTICULATE MATTER
Even the earliest humans suffered from particulate matter exposure: Dust storms from the Sahara, and
pollen and particulate fecal matter from grazing herds on the savannah caused respiratory, cardiovascular,
and skin disease. Today, city environments are filled with larger PM and PM particles (≤ 10 μm and
2.5
10
≤ 2.5 μm diameter, respectively) of soot, primarily emitted by diesel engines, factories, power plants, and