Free Radicals Theory Of Ageing: The free radical theory of aging (FRTA) states that organisms age because cells collect free radical damage over time. A free radical is any atom or molecule that has a single unpaired electron in an outer shell. While a few free radicals like melanins, that are not chemically reactive, most biologically-relevant free radicals are extremely reactive. For most biological structures, free radical damage. It is closely connected with oxidative damage. Antioxidants are reducing agents, and limit oxidative damage to biological structures by passivating them from free radicals.
Strictly speaking, the free radical theory is only concerned with free radicals like superoxide (02) but it has since been expanded to include oxidative damage from other reactive oxygen species such as hydrogen peroxide (H2O₂), or peroxynitrite (OONO).
Denham Harman first projected the free radical theory of aging in the 1950s, and the 1970s comprehensive the idea to implicate mitochondrial production of reactive oxygen species.
In some model organisms, such as yeast and Drosophila, there is evidence that reducing oxidative damage can extend lifespan. However, in mice, only 1 of the 18 genetic alterations (SOD-1 deletion) that block antioxidant defenses, a shortened lifespan. Similarly, in roundworms, blocking the creation of the naturally occurring antioxidant superoxide dismutase has newly been shown to increase lifespan. Whether falling oxidative damage below normal levels is sufficient to extend lifespan remains an open and controversial question.
Many studies have confirmed a role for free radicals in the aging process and thus tentatively support the free radical theory of aging. Studies have shown a significant enhancement in superoxide radical (SOR) formation and lipid peroxidation in aging rats. The ROS production increases with age and indicated the conversion of XDH to XOD may be a significant contributing factor.
Mitochondrial Theory Of Aging
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The mitochondrial theory of aging was first projected in 1978, and shortly subsequently the mitochondrial free radical theory of aging was introduced in 1980. The theory implicates the mitochondria as the main target of radical damage since there is a known chemical mechanism by which mitochondria can create Reactive oxygen species (ROS), mitochondrial components such as mtDNA are not as well protected as nuclear DNA, and by studies comparing harm to nuclear and mtDNA that display higher levels of radical damage on the mitochondrial molecules The electrons may free from metabolic processes in the mitochondria like the Electron transport chain and these electrons may in revolve react with water to form ROS such as the superoxide radical, or via an indirect route the hydroxyl radical. These radicals then damage the mitochondria’s DNA and proteins, and these damage components in turn are additional likely to make ROS byproducts. Consequently, a positive feedback loop of oxidative stress is established that, over time, can guide to the deterioration of cells and later organs and the whole body
This theory has been commonly debated and it is still unclear how ROS-induced mtDNA mutations develop. Researchers are recommending iron-substituted zinc fingers may produce free radicals due to the zinc finger proximity to DNA and thus lead to DNA damage.
They suggest the superoxide dismutation activity of CuZnSOD demonstrates a significant link between life span and free radicals.
Contrary to the typically observed association between mitochondrial ROS (mtROS) and a decline in longevity, recently observed increased longevity mediated by mtROS signaling in an apoptosis pathway. This serves to support the possibility that observed correlations between ROS damage and aging are not essentially indicative of the causal involvement of ROS in the aging process but are additional likely due to their modulating signal transduction pathways that are part of cellular responses to the aging process:
Epigenetic Oxidative Redox Shift (EORS) Theory of Aging
Brewer projected a theory that integrates the free radical theory of aging with the insulin signaling belongings in aging. They suggest ‘sedentary behavior connected with age triggers an oxidized redox shift and impaired mitochondrial function. This mitochondrial impairment leads to additional sedentary behavior and accelerated aging.
Metabolic Stability Theory Of Aging
The metabolic stability theory of aging suggests the cell can keep a stable concentration of ROS. It is the primary determinant of lifespan. This theory criticizes the free radical theory because it ignores that ROS are definite signaling molecules that are necessary for maintaining normal cell functions.
Oxidative stress may encourage the life expectancy of Caenorhabditiselegans by stimulating a secondary response to initially enhancing levels of reactive oxygen species. In humans, the question of the net effect of reactive oxygen species on aging is even less clear. Current epidemiological findings support the process of mitohormesis in humans and even recommend that the intake of exogenous antioxidants may increase disease prevalence in humans (according to the theory because they avoid the stimulation of the organism’s natural response to the oxidant compounds which not only neutralizes them but provides other benefits as well).
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