Crow's feet, atrophic and loose cheeks, "marionette" wrinkles, perpendicular to the lips, soft skin, dry and rough, bags on eyelids: this is the identikit of the employee by the inveterate cigarette.
The habit of smoking is equivalent to 10 years of indiscriminate exposure to the sun without any protection.
The concept of "smorker's face" was coined in 1985 by Douglas Model. Smoker's face: an underrated clinical sign?, 1985
These facial features were present in 8% of those who had smoked cigarettes for 10 years or more in the past and in none of the non-smokers.
Smoker's face was defined as one or more of the following:
- lines or wrinkles on the face, typically radiating at right angles from the upper and lower lips or corners of the eyes, deep lines on the cheeks, or numerous shallow lines on the cheeks and lower jaw;
- a subtle gauntness of the facial features with prominence of the underlying bony contours. Fully developed this change gives the face an "atherosclerotic" look; lesser changes show as slight sinking of the cheeks. In some cases these changes are associated with a leathery, worn, or rugged appearance;
- an atrophic, slightly pigmented grey appearance of the skin;
- a plethoric, slightly orange, purple, and red complexion different from the purply blue colour of cyanosis or the bloated appearance associated with the pseudo-Cushing's changes of alcoholism.
Tobacco smoking is one of the numerous factors contributing to premature skin
aging, which is independent of age, sex, pigmentation, sun exposure history, alcohol consumption and other factors.
Skin aging is a complex biologic process which includes intrinsic and extrinsic aging. Intrinsic aging affects the skin in a manner similar to other organs. Superimposed on this process, environmental factors such as tobacco smoke and ultraviolet (UV) radiation
contribute to extrinsic aging.
Normal human skin is dependent on the balance between the biosynthesis and degradation of extracellular matrix (ECM).
Matrix metalloproteinases (MMPs) play a key role in ECM
remolding in the skin.
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Normal human dermis consists primarily of an ECM
connective tissue collagen
, which accounts for about 80% of the dry weight of the skin. Alterations in the amount of collagen or disturbance of its degradative pathway results in clinical symptoms of cutaneous aging.
has been shown to decrease type I procollagen mRNA.
By inducing the expression of MMP
-1 and MMP
-3, but not the expression of TIMP
s, tobacco smoke extract could alter the ratio in favor of the induction of MMP
s and thereby cause a more degradative environment that produces loss of cutaneous collagen. Cigarette smoking is associated with elastotic changes in the skin, 1999.
White persons are more affected than black persons. The proclivity for the development of facial wrinkling may be due to a genetic sensitivity or perhaps from a greater susceptibility of the person’s cutaneous vasculature to damage from chemicals within tobacco.
The total dermal area occupied by elastic fibers is twice as large in patients who regularly smoked cigarettes. Among smokers these fibers are more numerous, more fragmented, and more expansive.
The stratum corneum in skin from patients who smoked containes less water.
The vascular structure of the skin may play a role in these elastotic changes. The cutaneous microvasculature is constricted by acute and long-term smoking. The decreased capillary and arteriolar blood flow may induce local dermal ischemia.
Tobacco stimulates neutrophils to release elastase in abnormal quantities. Because the elastin
tissue is degraded structurally, abnormal elastic tissue is believed to be produced in increased amounts similar to that described in the lungs. Increased cutaneous elastosis is not from slowed degradation of existing elastic fibers but rather from exaggerated elastin and microfibril production by fibroblasts. It’s believed that the presence of a continuous source of heat, that of a lit cigarette, may have promoted the increased elastosis found in the skin of patients who smoke.
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Smoking produces systemic immunomodulatory effects through the release of reactive oxygen species
from tobacco smoke,which is believed to cause a cascade of detrimental effects on normal inflammatory cell function by attenuating phagocytosis and bactericidal mechanisms, as well as by increasing the release of proteolytic enzymes. In addition, collagen synthesis and the deposition of mature collagen in the extracellular matrix are reduced through smoking. Such disruptive influences on these biologic mechanisms culminate in adverse affects on the cellular reparative pathways of the skin and its appendages, which can be observed in the healing of acute wounds in smokers. Cellular and molecular mechanisms of cigarette smoke-induced lung damage and prevention by vitamin C, 2008
. Modified proteins become vulnerable to degradation by proteases present in their vicinity. Microsomes contain proteases. Microsomal protein degradation is a function of the concentration of p-BSQ.
A vicious cycle might be operating, because cells undergoing apoptosis display increased oxidative stress, which further contributes to the apoptosis. The markers of apoptosis include DNA fragmentation, activation of caspase 3 and over expression of the proapoptotic Bax.
The ratio of Bax and Bcl-2 determines whether a cell will undergo apoptotic death or not.
What's in a cigarette?
Cigarette smoke is a highly complex mixture containing about 4000 compounds, including free radicals and longlived radicals.
Three Main Components of Cigarettes:
- Nicotine: This is the addictive component of tobacco. It is absorbed into the blood and affects the brain within 10 seconds. It causes smokers to feel good because of the neurotransmitters (chemicals in the brain) that it releases. It also causes a surge of heart rate, blood pressure, and adrenaline (which also feels good). Unfortunately, because of the nature of addiction, when the effects of nicotine on the brain and body wear off, the smoker feels worse than before. This reinforces the craving for another cigarette.
- Tar: is defined as the TPM (Total Particulate Matter) less water and nicotine. Tar itself contains many poisonous substances to the body. It is a thick, sticky substance, and when inhaled it sticks to the tiny hairs on the lungs, the cilia. These normally protect the lungs from dirt and infection, but when covered in tar they can't do their job. Tar also coats the walls of the whole respiration system, narrowing the bronchioles and reducing elasticity of the lungs.
- Carbon Monoxide: is the poisonous chemical found in car exhaust fumes. It decreases the amount of oxygen in the blood, which deprives all the organs of oxygen too. Because there's less oxygen in the blood, it gets thicker and puts a strain on the heart to pump.
Free radicals are found in both the gas/vapor phase and the particulate phase of the cigarette smoke aerosol. The gas-phase radicals have been shown to be unstable and very reactive, whereas the radicals in the TPM are much longer lived. P-benzosemiquinone, a long-lived radicals, causes oxidative damage. Involvement of semiquinone radicals in the in vitro cytotoxicity of cigarette mainstream smoke, 2006
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The cytotoxicity of quinols and quinones has been suggested to be due to the concerted action of several processes that include redox cycling; alteration of thiols balance through oxidation or arylation; inhibition of cellular functions; alteration of Ca2+
homeostasis; and covalent binding to nucleic acids, proteins, and lipids.
p-BSQ is present exclusively in the tar phase of CS.
The content of p-BSQ in AECS
: the lower the tar content, the lower was the amount of p-BSQ. The mitochondrial respiratory chain is affected by nicotine leading to an increased generation of superoxide anions and hydrogen peroxide.
Mitogenic and functional responses by nicotine and hydrogen peroxide, 2008
Oxidative stress arises when there is an imbalance between the formation of reactive oxygen species (ROS) and removal of oxyradicals by scavenging antioxidants, such as vitamin C and other.
Increase in ROS production has been directly linked to the oxidation of cellular macromolecules, which may cause direct cellular injury or induce a variety of cellular responses through the generation of secondary metabolic reactive species.
p-Benzosemiquinone appears to be a major causative factor of cigarette smoke-induced oxidative protein damage that are MMPs, VEGF and VEGFR2. Cellular and molecular mechanisms of cigarette smoke-induced lung damage and prevention by vitamin C, 2008
Upon treatment with tobacco smoke extract or UVA1
irradiation, the expression of MMP
-1 and MMP
-3 mRNA was significantly increased in a dose-dependent manner Alterations of extracellular matrix induced by tobacco smoke extract, 2000
s are primary mediators of connective tissue damage in skin exposed to tobacco smoke extract and thereby cause premature aging of skin in smokers.
p-Benzosemiquinone leads also to apoptosis through activation of caspase 3, degradation of PARP
ribose polymerase) and increased Bax/Bcl2 ratio
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is known as a signal for mitogen-activated protein kinase (MAPK
) pathway and has been shown to be involved in growth, differentiation and development in mammalian system.
It has been shown that ERK1
/2 is activated by H2O2
and by nicotine.
A vicious cycle might be operating, because cells undergoing apoptosis display increased oxidative stress, which further contributes to the apoptosis.
Vitamin C against smoke damage
An experiment shows that in smoke exposed guinea pigs fed 15 mg vitamin C/day, there is practically no increase in the amount of apoptotic cells.
15 mg vitamin C also completely prevents the increase of Bax protein in exposed guinea pigs, resulting in no increase of the Bax/Bcl2 ratio.
Vitamin C reduces p-BQ and thereby prevents protein carbonyl formation (degraded proteins).
This suggest that vitamin C plays a important role as strong antioxidant.
Cigarette smoke consumes vitamin C, so the fall in the vitamin C level was apparently due to consumption of vitamin C exclusively by smoke.
Ascorbic acid is the only plasma antioxidant depleted by smoking per se.
Once protein oxidation was prevented, the subsequent events of apoptosis and damage might also be prevented.
Once the tissue was damaged by exposure to CS,
administration of vitamin C/day could not reverse the process.
In other words, vitamin C is important in preventing the oxidative damage, not in the cure of it.
The concentration of ascorbic acid has been found to be lower in the serum of smokers compared with nonsmokers. Dietary Vitamin C Intake and Concentrations in the Body Fluids and Cells of Male Smokers and Nonsmokers, 1991
Smokers require a 40% higher daily intake than non-smokers to maintain comparable serum levels. Both vitamin C dietary and serum values were lower in smokers than non-smokers.
The alveolar macrophages of smokers contain greater amounts of vitamin C than those of nonsmokers, and that the rate of accumulation of ascorbate and dehydroascorbate is greater in the alveolar macrophages from smokers. The alveolar fluid and alveolar macrophages are the first line of defense against the oxidants liberated by tobacco smoke.
Within the group of smokers and nonsmokers, ascorbic acid concentrations in bronchoalveolar lavage and alveolar macrophages tended to increase as the number of cigarettes per day.
The risk of severe hypovitaminosis C was increased in smokers, particularly when not accompanied by vitamin supplementation. Even though smoking adversely affects preferences for vitamin C rich foods, the inverse association between smoking and serum vitamin C levels occurs independently of dietary intake. The Influence of Smoking on Vitamin C Status in Adults, 1989
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Smoking status was the most important non-nutritive predictor of serum vitamin C levels.
A consistent difference was detected in serum vitamin C levels between smokers and non-smokers of approximately 0.2 mg/dl, independent of the level of dietary vitamin C intake.
Approximately 130 mg of additional dietary vitamin C daily would be required to overcome the adverse effect of cigarette smoking on serum vitamin C levels.
Effects of Vitamin C depletion on collagen
The nonsmokers had a 1.8 times higher median amount of hydroxyproline than the smokers.
Ascorbic acid is an essential cofactor for lysyl hydroxylase and prolyl hydroxylase
, enzymes essential for deposition of hydroxyproline, that is negatively correlated with the consumption of tobacco.
In addition, L-ascorbic acid preferentially stimulates collagen synthesis.
The impairment is specific for the production of collagenous proteins and not other proteins.
Collagen is the main factor in the determination of the tensile strength of a wound, and the accumulation of this protein in a subcutaneous wound is dependent on perfusion and tissue oxygen tension, which is reduced significantly for nearly 1 hour after smoking only one cigarette.
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Nicotine causes a release of adrenal catecholamines, resulting in vasospasm and subcutaneous hypoperfusion with a simultaneous increased oxygen demand. Nicotine has also been shown to inhibit the function of erythrocytes, fibroblasts, and macrophages. Carbon monoxide has a high affinity for hemoglobin, reducing the amount of oxygen to be carried by the molecule.
Thirty minutes after smoking one cigarette, there is a mean decline in subcutaneous oxygen tension of 32%.
There is a unique metabolic pathways for the production of mature collagen. The cross-linking of the procollagen molecules to form a stable triple helix is dependent on the conversion of proline to hydroxyproline by prolyl hydroxylase and lysine to hydroxylysine by lysyl hydroxylase. These pathways in particular require molecular oxygen.
Cadmium, which is also a contaminant of tobacco smoke, has been found to depress the procollagen production in fibroblast. Less collagen production in smokers, 1998
A lot of natural antioxidants, especially carotene
are depleted in smokers.
A Dietary Oxidative Balance Score of Vitamin C, β-Carotene in Male Smoking, 2002.
It’s demonstrated that they provide protection against oxidation also in the skin.