Theories explain aging

2021-04-29 02:30 PM

Accumulation of LDL molecules is oxidized by free radicals, attracted by the macrophages, forming foam cells leading to atherosclerosis.

There are many ways to explain ageing. In the early 20th century, when bacteria were discovered and bacteria were considered the sole cause of illness, it was theorized that ageing was the result of multiple infections. However, the scientific theories rely on the latest achievements of recently emerging medical and biological studies to explain ageing.

Theories were once supported

Catastrophic error

This hypothesis was proposed by Orgel in 1963 based on the role of the cell. When replication takes place in the intracellular version of DNA and RNA, the frequency of possible errors including potential changes, methyl group binding to RNA, erroneous amino acids association In the synthesis of proteins, less specific or ineffective enzymes is produced in the organism. Any alteration of the structure of the energy production system can disrupt ATP energy production and oxygen consumption. Errors can be very small at first but will lead to catastrophe later: ageing and death.

The theory of the cost of life (Pearl, 1928)

Based on mammalian reviews the smaller the stature, the stronger the basal metabolism and the lower life expectancy. Hence, each individual species of species can only use a suitable amount of food with its body weight. If you have to metabolize strongly (eat a lot), you will quickly consume all the food allowed. Experiments on rats with different calorie-based diets showed that the more restricted the diet (but still met the minimum needs of the body), the longer the rat lived.

Somatic mutation

The somatic mutation theory is based on the assumption that somatic cells are subject to mutations frequently, albeit with a very low frequency. Mutations can be natural or impacted by an external environment, provoking a change in function and ultimately compromising organizational and organ structures. Vegetative mutations are seen as the fundamental mechanism of ageing, which occurs randomly, depending on time and location, perhaps equally occurring in gene segments.

Neurological - endocrine theory

Testosterone stimulates muscle protein synthesis, reduces breakdown and improves the reuse of amino acids to maintain muscle mass balance in young people. However, this hypothesis does not fully explain the changes in fat mass, the number of muscle cell nuclei, and the number of satellite cells in the elderly muscle mass. It is thought that testosterone may start pluripotent stem cells into muscle cell lines and inhibit their differentiation into fat cells.

Disorders of the endocrine glands most apparent during menopause. Disorders occur in the gonads, pituitary glands with many different hormones (ACTH, TSH, FSH, etc.) for different diseases, seen in old age; but it cannot be seen as the common source of ageing.

Mistake of the immune system (Makinodan, 1970)

Many studies show that the change of the immune response system is the cause of the development of diseases in old age from the age of 30 and plays a decisive role in ageing. The thymus atrophy at this age, but ageing is not always accompanied by a decrease in T lymphocytes or cell-mediated immune response. However, experiments on mice with thymectomy seem to have the above conditions related to the thymus gland and thymus essence: mice develop lupus erythematosus and early ageing, if thymus transplant returns, the disease improves.

Burnet hypothesized the emergence of autoimmune disease due to mutations at the cellular level. The MHC molecule controls the interaction between B and T lymphocytes, all of which increase or suppress the immune response is controlled by genetic mechanisms. The presence of cancer or an autoimmune disease is only the result of some change in the "thymus alarm" that leads to the wrong genes that are immunodeficient.

Theories still exist today

Theory of free radicals

The free radical theory was proposed in 1965 by Harman and is of current interest.

Effects of free radicals

Free radicals are molecules that are very unstable because they carry free electrons in the outer ring and are therefore strongly bound. The term reactive oxygen species (reactive oxygen species) describes oxygenated free radicals such as O2.-, OH. and other oxygen derivatives such as hydrogen peroxide (H2O2) and hypo chloric acid (HOCl). They have a tendency to oxidize surrounding molecules causing irreversible damage, especially the phosphorylation function. When attacking cells, free radicals can cause:

Protein degradation.

Lipid peroxidation leads to the destruction of cellular lipid membranes.

Attacks on DNA double-stranded DNA and lead to incorrect reading of base pairs.

Accumulation of LDL molecules is oxidized by free radicals, attracted by the macrophages, forming foam cells leading to atherosclerosis.

Free radical damage can activate certain enzymes, for example, protein kinases.

Free radicals and active oxygen: Free radicals can be produced from the following sources

Oxidation and reduction of oxygen, which occurs partly as part of normal metabolism.

Phagocytes are active in a controlled inflammatory response that produces HOCl and O2.

Sometimes caused by a response to exposure to ionizing radiation, ultraviolet rays, xenobiotic substances, drugs, environmental pollution, tobacco smoke, oxygen overload, exercise, ischemia.

The body's antioxidant systems

Mechanism of prevention: works to prevent the formation of new forms of active oxygen, eg ceruloplasmin (Cu), metallothionine (Cu), albumin (Cu), transferrin (Fe), myoglobin (Fe).

Has a clean-up effect: removes the newly formed active oxygen forms, thus preventing chain reactions of free radicals.

Antioxidant enzymes: superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), catalase (CAT), and metalloenzymes. These enzymes act to scavenge free radicals, catalyse chemical reactions to turn free radicals into non-toxic ones.

Other molecules: glutathione, vitamin C, vitamin E, bilirubin, uric acid, carotenoids, and flavonoids.

Repair enzymes: repair or remove molecules damaged by free radicals or active oxygen. These enzymes are DNA repair enzymes, methionine reductase.

The role of free radicals and ageing

Several studies have shown a link between the chain reaction of free radicals to the ageing process. The production of highly active free radicals causes accidental damage to DNA, RNA, enzymes, proteins, unsaturated fatty acids, membrane phospholipids. This damage accumulates, eventually leading to cell death. These reactions can be reduced by increasing the antioxidants in foods such as vegetables, fruits or by taking vitamins C, E, β carotene. The skin has antioxidants but the activity of these enzymes is reduced due to oxidative stress and old age.

Theory of accumulation of waste products (glycosylation theory)

The theory of randomness was first put forward by Bjorksten. It is based on multiple macromolecules (proteins and nuclear acids) that may gradually lose their metabolic activities due to the presence of covalent bonds between one molecule and the other. The existence of the crossing link hypothesis has paved the way for studies on link organizations, which can be considered as a model for studying changes in ageing processes. The basic Protide here is collagen. Collagen is distributed in the form of fibres throughout the body: tendons, skin, bones, etc., most of the glycosylated collagen in the elderly increases with age and decreases significantly with a calorie-restricted diet. The increase in cross-linking with age results in the correspondence of incomplete degenerative macromolecules or cell accumulation products that contribute to the main cause of ageing.

Theory of Genetics (the theory of evolution and selection)

Starting with Medawar and Haldane (1957), after being added, completed and developed by many successors into two concepts:

The aging process has an endogenous mechanism

It is even pre-programmed to rule out mechanisms that have ceased to reproduce and adapt to the replacement by a new generation that easily suffers from natural selection, thus inducing the evolution of species.

The experiment of Hayflick and Morehead (1961).

Vertebrates are composed of two types of cells: (1) renewable cells (also called inter-mitotic cells), such as epithelial cells; (2) non-renewing cells (also called post-mitotic cells), eg nerve and smooth muscle cells. Thus, all vertebrates after birth have a certain amount of post-mitotic cells. These cells are lost during the survival process, there is no substitute. But before disappearing, these cells will be stagnant "residue" like lipofuscin.

For intercellular cells, in 1961 Hayflick and Morehead demonstrated that human diploid fibroblasts have only limited proliferation capacity in the culture medium. Only abnormal cells with more than 46 chromosomes are capable of forever dividing as cancerous cells. In addition, he demonstrated the inverse between the age of the donor and the viability of the cultured cells. Each year the donor lives, respectively, 0.2 times the cell duplication. Fibroblast division is markedly reduced in "old dwarfism" and Werner syndrome, which reflects premature ageing and is notably the emergence of premature degenerative changes, significantly reducing the likelihood of cell division.

The notion that ageing plays a role in the external environment

If an individual does not die of old age, it will die from any other reason (birth accident, infection, lack of food, competition for survival with another species, etc.). At some point, the number of individuals in the species will be balanced and stable. There are many genes that are beneficial to an individual at a young age but harmful in old age, such as the gene that helps cells thrive (helps the individual to grow faster) that will become oncogene: these are called opportunistic ageing genes although they have been useful in the past. On the other hand, because mutations will appear completely detrimental to genes, then ageing and death will help individuals avoid that disadvantage. Thus, the expected evolutionary view before ageing is just a continuation in the organic development of organisms: the next stage of embryogenesis, puberty, and adulthood. The risk of death increases over time as a result of:

There exists a high selection of genes for which the beneficial effect develops early; although the gene later becomes harmful (the "opportunity" gene).

Reducing selection pressure against harmful genes expressed in the late stage (the "true" old "gene)

In other words, the second concept is that it is the selection process for evolution that causes ageing, not the exclusion of the ageing body that helps evolution.



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