What is the free radical theory? The free radical theory.

The Free Radical Theory

Olinescu et al (2002) defined free radicals as molecules that contain one or more unpaired electrons. It is these unpaired electrons which alters their chemical sensitivity, making them highly chemically reactive (Halliwell 1996). The radicals strive to obtain balance by reacting with non-radicals, when this reaction occurs another free radical is formed, thus participating in a characteristic feature of free radicals, a chain reaction. This chain reaction may involve thousands of reactions. It may either occur in the cell cytosol and cytosol, or in the plasma membrane (Sies 1997). The process is known as lipid peroxidation when it occurs in the cell membrane. Dekkers et al (1996) found that this leads to a number of cellular changes, formation of toxic metabolites, increased cell membrane permeability and decreased calcium transport. These free radicals may cause damage resulting in unwanted mutations increasing the risk of cancer. The free radical theory was first proposed by Harman in 1956, at this time it was only strictly concerned with free radicals. In 1972, Harman included oxidative damage by reactive oxygen species such as hydroxyl, superoxide radicals (O2−), hydrogen peroxide (H2O2) and singlet oxygen (O2). After the redefinition in 1972 it was renamed the mitochondrial theory of aging in certain scientific circles, this name has since gained a more general acceptance.

The free radical theory states that aging of cells is caused by accumulated free radical damage over time. Mehlhorn (1994) found that the production of the most common type of free radicals, radical oxygen species, occurs mostly within the mitochondria of the cell.

Mitochondria produce the chemicals which a cell uses for energy. This is done through the process called “the electron transport chain”, in which electrons are passed between molecules, creating useful chemical energy with each pass. However, as oxygen occupies the final position in the electron transport chain, the passed electron might interact incorrectly with the oxygen, resulting in reactive oxygen species. Ozawa (1999) stated that most of the radical damage occurs in the mitochondrial DNA (mtDNA). This is explained in the “mitochondrial theory of aging” through the somatic accumulation of mtDNA mutations during human life. This damage accumulation eventually leads to mitochondrial dysfunction and apoptosis. The mutations results in human aging and geriatric processes; including gradual loss of cellular bioenergetic capacity, reduced muscle strength, declining mental capacity and reduced ventricular performance. This has later been backed up in several studies. Bender et al (2006) demonstrated that subjects with Parkinson disease and elderly people with declining mental capacity show high levels of mitochondrial deletion mutations in their substantia nigra neurons. This was also confirmed by Kraytsberg et al (2006) who demonstrated the same abundance of mitochondrial DNA deletion mutations in substantia nigra neurons as a direct cause of decreased mental capacity and function.

_References:

_{Bender, A., Krishnan, KJ., Morris, CM., Taylor, GA., Reeve, AK,. Perry, RH., Jaros, E., Hersheson, JS., Betts, J. and Klopstock, T. (2006). High levels of mitochondrial DNA deletions in substantia nigra neurons in aging and Parkinson disease, Nat. Genet. 38, 2006, pp. 515–517.}

_{Dekkers, JC., Van Doornen, IJP., Kemper, HCG. (1996) The Role of Antioxidants Vitamins and Enzymes in the Prevention of Exercise-induced Muscle Damage. Sports Medicine 21 (3) 213-38.}

_{Halliwell, B. (1996) Antioxidants in human health and disease. Annual Review of Nutrition. 105 (4) 989-92.}

_{Harman, D. (1972). "A biologic clock: the mitochondria?". Journal of the American Geriatrics Society 20 (4): 145–147.}

_{Kraytsberg, Y., Kudryavtseva, E., McKee, AC., Geula, C., Kowall, NW. and Khrapko, K. (2006) Mitochondrial DNA deletions are abundant and cause functional impairment in aged human substantia nigra neurons, Nat. Genet. 38, 2006, pp. 518–520.}

_{Mehlhorn, RJ. (1994) Physiological Basis of Aging and Geriatrics, edited by Paola S. Timiras (CRC Press, Ann Arbor, 1994), pp. 61-72.}

_{Olinescu, R., Smith, T. Dr. (2002) Free Radical Definition. In: “Free Radicals in Medicine” Chapter 1., pp.2. Nova Science Publishers, Inc. Huntington, New York.}

_{Sies, H. (1997). Oxidative stress: oxidants and antioxidants. Experimental Physiology Volume 82 (Issue 2): Pages 291–5.}