HUMAN MEDICAL BIOLOGY, ANATOMY, PHYSIOLOGY AND PATHOLOGY - Ya.I.Fedonyuk 2010

BIOLOGY

CHAPTER 1. BIOLOGICAL FOUNDATIONS OF HUMAN VITAL ACTIVITY

1.4. ONTOGENETIC LEVEL OF LIFE ORGANIZATION

1.4.3. Biology of Individual Development

Theories of Aging

There are over 200 theories and hypotheses of aging. I.I. Mechnikov believed that the cause of aging is the intoxication of the entire Organism, and particularly of The Nervous system, by toxic waste products of putrefactive Bacteria in the Large Intestine. To prolong life, he recommended consuming Bulgarian sour milk containing lactic acid bacteria, which were supposed to displace the putrefactive bacteria of the gut. Mechnikov's theory is significant for combating premature aging, but it does not reveal the mechanisms of physiological aging. Furthermore, it does not explain the causes of aging in organisms that lack a large intestine. According to O.O. Bogomolets' theory (1881–1946), the primary role in the aging process belongs to the state of Connective Tissue, which, in his view, ensures the physiological activity of the entire organism. To stimulate connective tissue function, he proposed antireticular cytotoxic serum (ACS). Theories attributing the cause of aging to the declining function of Endocrine glands also became widespread. A proponent of the endocrine theory of aging was the French physiologist C. Brown-Séquard (1889), who assigned the main role in aging processes to the Gonads. To rejuvenate aging organisms, gonads from young organisms were transplanted (S.O. Voronov and others). However, this method proved ineffective because the graft was reabsorbed and signs of aging reappeared. I.P. Pavlov and his students believed that aging processes are influenced by the Central Nervous System, especially the Cerebral Cortex. It was experimentally proven that nervous overstrain and "disruptions" of nervous activity in dogs cause premature aging. V.V. Frolkis developed the adaptation-regulatory theory of aging. The aging process involves the mobilization of important adaptive mechanisms aimed at preserving the organism's viability and increasing life expectancy. A manifestation of such processes is an increased sensitivity of Cells to MEDIATORS AND Hormones under conditions of reduced synthesis of these substances in the aging body. There is an increase in Glycolysis intensity, hypertrophy of certain cells, and The Emergence of polyploidy and multinucleation within them (Liver cells).

The aging process is regulated by genes. Evidence supporting the Genetic control of aging is that maximum lifespan is a species-specific trait. In humans, a positive correlation has been found between the lifespan of offspring and parents, particularly the mother. Hereditary diseases involving premature aging have been described. For example, in Hutchinson-Gilford syndrome (juvenile progeria, or premature aging in childhood), growth retardation is observed as early as the first year of life; children exhibit an aging appearance, sparse grey Hair, proportionate dwarfism, early baldness, Skin wrinkling, and The Development of atherosclerosis. Sexual maturity is generally not reached, and death occurs before the age of 30. The inheritance pattern of the disease is autosomal recessive.

Hypotheses explaining the mechanisms of aging can be divided into two groups: stochastic and programmed. According to stochastic hypotheses, aging is based on the accumulation of "errors" and damage that occur randomly (stochastically) during the individual's life activity at various LEVELS OF STRUCTURAL Organization. Proponents of various versions of these hypotheses emphasize the paramount role of damage to the genetic apparatus (the somatic mutation accumulation hypothesis) or damage to biological molecules, including RNA, nuclear and cytoplasmic Proteins, and Cell Membrane Lipids (the free radical hypothesis, the Enzyme Structure damage hypothesis).

According to programmed hypotheses, aging is genetically determined, meaning that information regarding its onset and progression is encoded in The Cell genome. The presence of programmed aging is supported by the existence in nature of species in which reproduction is followed by intensive changes leading to the death of the animals. For instance, Pacific salmon (pink salmon, sockeye salmon) die after spawning. Programmed hypotheses of aging are based on the assumption that a specific "clock" operates within the organism, governing age-related changes, although the exact mechanism of this clock has not yet been established.

Confirmation of the existence of a genetically encoded "program of life" comes from L. Hayflick's research (1965) on embryonic fibroblast cultures. These cultures undergo a fixed number of generations (50±10 cell divisions), after which the culture inevitably dies. Only cells with an altered hereditary apparatus (Cancer cells) possess an unlimited capacity for proliferation. The time of manifestation for certain hereditary diseases is also programmed. For example, Huntington's chorea (St. Vitus' dance), a typical symptom of which is severe tremor of the HEAD and limbs, manifests on average at the age of 38–40, appearing later in men than in women.

Telomerase hypothesis. Telomeres are the ends of chromosome arms that prevent Chromosomes from sticking together and ensure their proper orientation during Cell Division. With each cell division, telomere length decreases due to the loss of terminal DNA segments, and the cell eventually loses its ability to divide. In children with progeria, telomere length is so short that cells very quickly lose their division capacity, which in turn accelerates the aging process. In experiments, scientists managed to alter the aging process in cells by introducing genes responsible for The production of the enzyme telomerase, which plays a crucial role in Telomere Synthesis, into the DNA. Telomerase (DNA nucleotidylexotransferase) is an enzyme that restores the ends of linear chromosomal DNA molecules with short repeating sequences (TTAGGG in vertebrates). Telomerase is present in Gametes and the fetus, but adult organisms lack it. Due to the reduction in telomere length, mammalian somatic cells have a limited number of divisions and enter a state of irreversible arrest known as "replicative senescence." This leads to a slowdown in cell renewal, which drives organismal aging.

Experiments studying METABOLISM/18.html">The Influence of living conditions on the aging process have yielded positive results. Average life expectancy increases in certain invertebrates (planarians, daphnia) and vertebrates under dietary restriction. The general Conclusion regarding The impact of living conditions is that factors that slow down development contribute to an increased lifespan.