A free radical is any atom or molecule that has a single unpaired electron in an outer shell. Whether reducing oxidative stability of free radicals pdf below normal levels is sufficient to extend lifespan remains an open and controversial question. 1950s, when prevailing scientific opinion held that free radicals were too unstable to exist in biological systems.
This was also before anyone invoked free radicals as a cause of degenerative diseases. Noting that radiation causes “mutation, cancer and aging”, Harman argued that oxygen free radicals produced during normal respiration would cause cumulative damage which would eventually lead to organismal loss of functionality, and ultimately death. In 1972, Harman modified his original theory to what became known as the mitochondrial theory of aging. This mitochondrial theory has been more widely accepted that it could play a major role in contributing to the aging process. Since Harman first proposed the free radical theory of aging, there have been continual modifications and extensions to his original theory.
Free radicals are atoms or molecules containing unpaired electrons. Free radicals, which contain only a single electron in any orbital, are usually unstable toward losing or picking up an extra electron, so that all electrons in the atom or molecule will be paired. Note that the unpaired electron does not imply charge – free radicals can be positively charged, negatively charged, or neutral. Damage occurs when the free radical encounters another molecule and seeks to find another electron to pair its unpaired electron. The free radical often pulls an electron off a neighboring molecule, causing the affected molecule to become a free radical itself. The free radicals produced in such reactions often terminate by removing an electron from a molecule which becomes changed or cannot function without it, especially in biology.
The chain reaction caused by free radicals can lead to cross-linking of atomic structures. DNA, the DNA can become cross-linked. Specifically, an increase in superoxide affects aging whereas a decrease in nitric oxide formation, or its bioavailability, does the same. XDH to XOD may be an important contributing factor. ROS production in DW mice may be a factor in their resistance to oxidative stress and long life. They suggest ROS signalling may be a determinant in the aging process.
60 years or older may be linked with increased oxidative stress. In addition, they suggest mitochondrial superoxide anion plays an essential part in aging. Thus several modifications have been proposed to integrate current research into the overall theory. Mitochondrial free radical theory of aging was introduced in 1980.