Theories of aging: free radicals

Keep in mind that aging is considered a multifactorial process that represents a gradual deterioration of physiological functions of homeostasis and allostasis. Of the many theories developed and investigated, one of the most currently accepted to meet the requirements that are asked to explain and define old age (universal associated with the processes that must occur to varying degrees in all individuals of a species, Intrinsic : endogenous causes, which are not dependent on extrinsic factors, Progressive occur during the development of life, damage: considered only as part of a process of aging (Bernard Strehler)) is the theory of aging free radicals.

It proposes that free radicals formed in the metabolism generating residual toxicity of oxygen-derived (and other oxidizing agents such as reactive nitrogen species) are responsible for the damages associated with the cells and thus cause for aging, which generates highly reactive molecular fragments that can lead to very disorganizing reactions and degenerative processes such as cancer, atherosclerosis, amyloidosis and immunodeficiency, decreased antioxidant levels, and deterioration in the repair of oxidative damage. Is oxidative damage in the cell. It really is an oxygen poisoning who are sentenced all aerobic organisms.

Origin of the free radical theory of aging as a cause
The first postulated the theory of free radicals in 1950 by Harman, whose very author returns to touch up that theory later in 1972. Many experiments and groups of scientists with different evidence supports this theory as one of the causes of aging. To defend this theory must be shown that since we have good anti-oxidation systems, even beneficial for certain metabolic pathways for the intermediate molecules that are generated (like two sides of the same coin, on one hand the other destructive and beneficial) .

In vitro studies show how different can counteract the oxidizing effect with implementation of antioxidants. In vivo these antioxidant systems are unable to counteract all free radicals continuously generated during the life of the cell. At a time point also increased free radicals accumulated purely physiological moments, which resolved in timely manner. It is the accumulation are along cellular life and the concern being studied in the theories of aging.

Free radical damage at the cellular level
Free radicals are a result cellular damage and tissue, affecting the performance of the organs. Will occur at DNA damage, with consequent deterioration at the level of protein production and damage to membrane lipids, altering the fluidity and thereby hinder good communication between and within cells. We therefore damage both structural and functional cell (molecules to growth signals, apoptosis, neurotransmission ,..). It implies a worsening of the organism to respond to stress and maintain homeostasis (responding to oxidative stress, thermal shock, radiation, alkylating agents, heavy metals, etc).

It has seen in older animals there is a greater accumulation of oxidation in young animals, counting the protein, lipid and oxidized DNA (Stadtman and Sohal). The increased length of life, also tends to raise the rate of free radicals involved in degenerative diseases.

One reason to support this theory is the application in therapy. There is the option of using antioxidant molecules and to observe the beneficial effects and reversal of cell destruction. Equilibrate over the balance of oxidant / radical production.

Free radicals and mitochondrial theory
In the theory of aging by free radicals, should be included as a specific mitochondrial theory of aging, which is the organelle within the cell's leading producer of ROS (reactive oxygen species) and (NO) nitric oxide, also responsible oxidation. There are other cellular organelles (peroxisomes, microsomes) also generate ROS to which must be added that in the presence of certain transition metal complexes can react with each leading to more extreme.

The mitochondrion is the main endogenous source of oxidants involved in aging. Reactive oxygen species are continuously generated in the electron transport chain in mitochondria. The production is cumulative, which is causing a chronic oxidative stress. The more breathing rate more likely to accumulate reactive oxygen species (ROS). It has been seen as those mitotic cells in continuous differentiation are not yet fully differentiated functionality (protected cells against aging by moderate consumption of oxygen and the regeneration of mitochondria that accompanies mitosis), there are fewer reactive species in those where the cell is mature and differentiated. Here the electron transport chain, cell respiration by mitochondria, has to operate at full capacity, to synthesize the abundant ATP needed for the specific function of the cell. We are highly specific in muscle (including heart), liver and nervous system cells. The production of oxidation by mitochondria is the key that determines the maximum potential longevity.

The mitochondrial theory has been tested by several laboratories. Sohal and Miquel and coworkers have shown that mitochondria of old animals produce more ROS than mitochondria from young animals. There is an inverse relationship between the production of peroxide (superoxide anion and hydrogen peroxide) mitochondrial and mammalian longevity. Also see the increase of damage in mitochondrial proteins and lipids. Corbisier and Remacle provide an experiment that reinforces this: microinjected mitochondria of old rats fibroblast cells of young rats, and rats that had received the mitochondria "old" quickly entered senescence.

Note that mitochondria are not only involved in the aging structure level but also at the level of functionality. It has been observed as mitochondrial activity decreases with age as has been said to affect primarily the liver, muscle and brain. The ratio of transcription of some mitochondrial genes decreases with age in mice and Drosophila. There RNA molecules highly susceptible to oxidative stress (16SrRNA), which can be regarded as cellular marker.

Many labs are more interesting to study biomarkers of oxidative stress to study the amount of production of oxidants. Some biomarkers studied: ethane and pentane to lipid peroxidation, protein oxidation and oxidation of DNA. Mitochondrial DNA is more affected by ROS than nuclear because it is one that is continuously exposed to them and not have histones and has protection mechanisms such as nuclear. This does increase the rate of mtDNA mutations, leading to the deterioration of the function of aerobic respiration, since mtDNA encodes proteins of the respiratory chain). Less production of electron transfer leads to increased production of ROS, thus establishing a vicious cycle between oxidative stress and decreased energy.

All this can block the mitochondrial division and organelle renewal, and lead to self-destruction process (autophagic digestion of mitochondria, thereby decreasing the production of ATP and protein needed for specialized cells work, and accumulation of aging pigment : lipofuscin), also compounded by dysfunctional lysosomal accumulation, leading to an irreversible cell death.

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*Automatic Translation