Smoking reduces longevity by 7-10 years. By the time the smoker notices health issues, serious health damage has occurred. Smoking has many of the deleterious effects on health. Cigarette smoke chemicals  accelerate the aging process. There are more than 4000 different chemicals in the smoke, many of which are carcinogens. The exact mechanisms by which smoking cause diseases are generally not well established. However, it is evident that smoking affect several main aging accelerators such as free radical, glycation, inflammaging, DNA damage (gene mutations), interference with body’s natural defense and repair mechanisms, telomere shortening.

Cigarette smoke contains several different chemicals that are free radicals (mainly carbon and nitrogen centered). (see “free radical theory of aging“). One is the tar and the other is the gas phase. The tar contains several relatively stable free radicals: quinone/hydroquinone complex. The quinone-hydroquinone-semiquinone system is an active redox system that is capable of reducing molecular oxygen to produce superoxide (free radical), which in turn leading to the accumulation of hydrogen peroxide and hydroxyl radicals – the two hyper reactive ROS (reactive oxygen species, free radicals) that can extensively damage protein, DNA, and cellular membrane. The gas phase of cigarette free radicals contains small oxygen- and carbon-centered radicals that are even more reactive than tar radicals. The gas phase radicals are produced in a steady state by the oxidation of NO to NO2 which then reacts with isoprene in the smoke. Research has found the linkage between smoke radicals and the development of various diseases such as emphysema and cancer. Free radical induced DNA damage (or gene mutations) is one of the mechanism that attribute to the smoke induced carcinogenesis.

Acetaldehyde is the other chemical in tobacco smoke that is also addictive (same as nicotine) and is not widely known. it is also a known carcinogen and therefore implicated in causing cancer. Exposure to acetaldehyde can lead to the formation acetaldehyde-derived advanced glycation end-products (AA-AGE). (see article “Glycation And Aging | crosslinking theory of aging” ). AGE are generally toxic to the body. Advanced glycation end-products (AGE) can bind to proteins and then inactivate the protein for its function. AGE receptors are present in a number of cells and tissues (endothelial cells, liver). The other mechanism AGE can harm the body is by binding to the AGE receptors which in turn, result in the production of cytokine or other inflammatory mediators that can induce unwanted and potentially harmful inflammation in blood vessels, nerve, liver and other tissues. Studies has found that AA-AGE (acetaldehyde-derived advanced glycation end-products) is toxic on hepatocytes. The glycation process also generate byproduct intermediates that are reactive oxygen species (free radicals) which further accelerate the aging process.

The body has evolved a range of defense mechanisms that counteract alterations of the physiological state occurring in the course of aging. Cigarette smoke chemicals interfere with and reduce the efficiency of these mechanism. Tobacco smoke chemicals reduce the efficiency of natural antioxidant enzyme defense system by reducing the concentration of selenium, zinc  which has vital roles in antioxidant enzyme capacity (see post “Selenium, Selenoproteins And Health“).

Telomere length shortens with age in all replicating somatic cells. (see post “Telomere Shortening and replicative senescence” and post “Telomere Shortening – The Secret to Aging?” and “Is telomere length a biomarker of stress and aging?“). It has been shown that smoking accelerates telomere shortening in lymphocytes. As peripheral leukocytes have been the main target of telomere research, most of what is known about human telomere dynamics in vivo is based on these cells. Studies confirmed that individuals with shorter telomeres present a higher prevalence of arterial lesions and increased risk of cardiovascular disease. Recent studies have discovered that therapeutic or nutritional maintenance of telomere length may confer healthy aging in smokers .

Smoke Induced Diseases

Most of the smoke chemicals generated during the combustion is inhaled. Consequently the first organ that come into contact with noxious chemicals (either hydrophobic or hydrophilic) are the oral and nasal cavities followed by the respiratory tract and lung. Hydrophobic compounds (the tar fraction of smoke) that precipitate in the oral cavity are swallowed and enter the digestive system. Inhaled chemicals further precipitate on the surface of respiratory tract. Hydrophobic chemicals can diffuse across cellular membrane and penetrate the mucosal linings and reach the circulation, and consequently all organs, including the skin. The hydrophilic chemicals reach the alveoli and are either diffused and transported through the lung-blood barrier system, or is retained in the lung. Many of the chemicals accumulates and cause damage to the tissues and organs after entering organs:

• skin damage (see post “How Smoking Cause Skin Aging“)
• cancer: cigarette smoke contains a large number of mutagenic compounds (carcinogens) including oxidants/radicals and PAHs. Smoking increases the rate of DNA (gene) mutations which not only accounts for the carcinogenic activity of cigarette smoke but also reduces the functionality of enzyme, cells, and organs. DNA mutations in the mitochondria (energy metabolism) further increases the oxidative stress.
• cardiovascular diseases: smoke chemicals (e.g.nicotine) narrows blood vessels over time making it harder for the blood to get through. Smoking causes cardiovascular diseases via several activities. Nitric oxide is an important regulator of vascular tone. Cigarette smoke contain superoxide radicals that interact with nitric oxide to form ONOO, decreasing the NO and the vasomotor function is reduced, resulting in endothelium dysfunction. Endothelium dysfunction is the major factor resulting in atherogenesis. Smoke induced chronic inflammation also contributes to the atherogenic disease processes. The accelerated vascular aging by cigarette smoke increases the risk of myocardial infarction, stroke, peripheral arterial diseases. Smoking exposure increases the risk of thrombosis which is also a major factor in the pathogenesis of smoking-induced cardiovascular events.
• lung diseases (chronic obstructive pulmonary disease COPD, lung cancer): cigarette smoke contains a high amount of particulate matter, including the particles less than PM2.5 that can reach alveoli. Smoking increases the burden of body’s natural removal system (surfactant, lung macrophages, and cilia) for particulate matter. Smoke chemicals also induce lung fibroblasts senescence which is vital for lung tissue renewal. Aging of lung fibroblasts may significantly contribute to smoke induced lung diseases. Oxidative stress and protease-antiprotease imbalance are identified as the cause of smoke induced COPD as well.
• bone: smoking increases the risk of osteoporosis by interfering with calcium and vitamin D homeostasis which are vital for bone metabolism. Smoking reduces estrogen which are regulators of bone metabolism. Oxidative stress (free radicals from smoking) also inhibits the differentiation of osteoblastic cells, resulting in reduced bone formation.
• brain: smoke chemicals may also contribute to brain aging through its effect on the cerebrovascular dysfunction. Reduced oxygen and nutrient supply is thought to be associated with decrease in the brain function. In addition, smoking induced inflammation may also contribute to the accelerated brain aging.
• eye: smoking is the only risk factor known to clearly contribute to age-related macular degeneration (AMD). Smoking accelerate the development of cataracts as well. Cigarette smoking causes a chronic systemic inflammatory status (inflammaging) which also damages the retina, beside other detrimental effects.
• teeth: exacerbate gum disease, increased risk of losing teeth.