Mammalian Aging Physiology

Body weight and composition

The bulk of the body, which is composed of the mass of muscles and tissues, after reaching puberty is constantly decreasing and in deep old age is about two-thirds of the maximum value in youth. In contrast, full body weight usually increases with age, as the amount of accumulated fat and water increases. The relative amount of extracellular fluid, which decreases during fetal and postnatal development , increases with age during adulthood. Despite the appearance, all fabrics, even leather , contain more water due to aging. Although muscle mass is also usually lost, the rate of loss depends on the physical activity of the individual. There is evidence that most of the loss of muscle mass with age is the result of detraining and atrophy , and not loss of muscle fibers.

A decrease in the bulk of the body is accompanied by a decrease in the level of metabolic activity . Basal metabolism (metabolism) is greatest during the period of the most rapid mass growth, after which it rapidly decreases until puberty, and then the decline slows down. In rats , during a slow decline, metabolic activity decreases by about 20 percent over a three-year period. The internal temperature of the body is maintained constant, despite the lower heat production, which is caused by a reduced flow of blood through the skin and a decrease in heat loss, as a result of which the skin temperature somewhat decreases. The amount of voluntary physical activity, such as running in a wheel, usually decreases with age, but depends heavily on the particular animal.

Changes in structural tissues

The structural integrity of the vertebral organism primarily depends on two types of protein fibers - collagen and elastin . Collagen, which makes up almost one third of the total mass of all body proteins, is found in the skin , bones and tendons . After synthesis by the fibroblast cells, the collagen is in soluble form (tropocollagen). Gradually soluble collagen polymerizes , turning into a stable form that can persist in tissues for most of the life of animals. The rate of collagen synthesis is high in youth and decreases throughout life, so that the ratio of the concentrations of filament and dissolved collagen increases with age. With age, collagen collagen turns into a protein network that resembles crystalline lens of the eye. With increasing age, the number of bonds between collagen molecules increases, leading to the creation of a crystalline rigid structure, which leads to an overall increase in body stiffness.

Another change that accompanies aging is a relative decrease in the amount of glycosaminoglycans (or mucopolysaccharides, which are complexes of proteins and carbohydrates), with the result that the ratio of hexoamine and collagen concentrations is used as an indicator of aging of a particular individual or person. An important consequence of these changes is a decrease in tissue permeability to dissolved nutrients, hormones , growth factors and antibodies .

The aging rate of collagen depends on the complete metabolic activity of animals: the rats that were kept on a low-calorie diet had a “younger” collagen than the rest of the rats of the same age.

Elastin is a molecule that is responsible for the elasticity of the blood vessel walls. With age, there is a loss of elasticity of blood vessels, primarily due to the fragmentation of collagen.

Cross-links between collagen molecules are chemically similar to cross-links that are formed in the skin during tanning. Due to this similarity, it was proposed to use chemicals to slow down old age, which interfere with polymerization processes. However, due to their high toxicity, the use of such substances in animals is not yet possible.

Cell Updates

Body tissues are divided into two groups depending on whether the cells of the tissue are renewed. In some tissues, cells are not renewed at all, for example, in nerves, myocardial cells and skeletal muscles , in which new cells are not created (at least in mammals) after a certain stage of growth of the organism. In other tissues, such as the intestinal epithelium and blood , on the other hand, some cell types are updated every few days and replaced hundreds of times over the life span of even short-lived animals. Between these examples there are many organs, such as the liver , skin , endocrine organs , where cells are replaced more slowly, with periods ranging from weeks to years in humans.

Peripheral nerves are a convenient object for research, because the total amount of fibers in the nerve column can be calculated. This was done for the cervical and thoracic spinal nerve root of a rat, cat, and human. In the human abdominal and spinal nerve root, the amount of nerve fibers decreases by about 20 percent from 30 years old to 90 years old. In cats, rats and mice, on the contrary, the data do not show a decrease in the number of dorsal root fibers with age. In humans, the number of olfactory nerve fibers decreases with age, by about 25 percent from birth to 90 years of age, much like the number of optical nerve fibers that provide vision.

A significant decrease in cells is observed with age and in the number of living cells in the human cerebral cortex. The rat and human cerebellum cortex is also very sensitive to aging. Other parts of the brain do not age significantly.

There is a tendency for higher and newly developed parts of the nervous system to deteriorate more rapidly with aging than older sections, such as the brain column and the spinal cord . It is not yet known what percentage of cells is lost due to the aging of the brain, and what percentage is due to other causes, such as poor circulation. The nutrition and maintenance of nerve cells, neurons , and the central nervous system largely depends on glia , the small cells that surround neurons. The absolute number of these cells does not decrease markedly with age, but some of the microscopic changes that are observed in the nerve cells of older people are similar to those caused by starvation or physical exhaustion.

It has also been shown that after some diseases, such as measles , the virus remains in the host body for the remainder of life and sometimes causes a rapid deterioration of the functions of the cerebral cortex. This virus, like some other not so obvious viruses, may also be responsible for individual differences in the rate of human aging.

Renewable tissues usually consist of a population of proliferating cells that retain the ability to divide, and populations of mature cells that originate from proliferating cells and have a limited life span. The production of these cells should compensate for their losses, including unexpected losses caused by damage or disease. Thus, each fabric has one or more ways to control production according to needs. Aging of such tissues is expressed in several ways, in particular, by a decrease in the number of proliferating cells, a decrease in the rate of cell division and a decrease in the activity of control systems. Changes of these factors in the blood-forming tissues of the mouse are small, but very clearly manifested in extreme conditions.

Intact skin renews its cells every few weeks, with the ability to temporarily increase the rate of cell production in response to damage. The rate of healing is gradually decreasing with age, at first quickly, and then somewhat slower.

One of the most stable signs of aging is the deterioration of the ability to focus the eye on both close and distant objects. This loss in visual accommodation is the result of weakening the muscles of the eye and reducing the elasticity of the lens. Another factor that contributes is that the lens continues to grow throughout life, albeit with a slower speed. This growth is the result of the continuous division of epithelial cells around the lens’s conditional center, creating new cells that differentiate into lens fibers. After creation, these fibers remain forever in the same place.

An important component of the renewal mechanism is stem cells . These cells, which usually continue to divide freely throughout life, under conditions of increased demand, pass into the phase of rapid proliferation . Blood tissue contains a stem cell population that responds quickly to damage in youth, but its activity decreases with age. The increase in cases of anemia in old age and the slowing down of the response to blood loss are usually explained by the depletion of stem cells of the blood-forming organs. In some other organs, stem cell populations were not found, for example, in the intestinal mucosa, despite the high rate of cell division.

Tissue morphology

Significant changes occur with age and in the morphology of tissues. For example, a small degree of tissue atrophy is common. The most noticeable reduction in the size of the thymus , especially given its role in the immune defense . A gradual decrease in the volume of cellular tissue and its replacement by adipose or connective tissue is the most significant in bone marrow and skin . In the kidneys, entire secretory structures ( nephrons ) are lost. The secretory cells of the pancreas , thyroid and some other organs are also reduced in quantity.

An important change during aging is the accumulation of pigments and inert and possibly harmful materials between cells. Lipofuscin pigment accumulates within the cells of the heart muscle - usually it is absent up to 10 years after the birth of a person , but its number increases to almost 3 percent of the cell volume at 90 years of age . The amyloid substance, a protein-carbohydrate complex , accumulates in the tissues at middle age, perhaps it is a product of autoimmune reactions . In the extreme case of amyloid disease , a rare autoimmune disease , some organs are actually suppressed by amyloid substance. Small amounts of metals also accumulate in different tissues with age, and although these amounts are small, some metals can cause enzyme poisoning, stimulate mutations, or cause cancer .

Cell cultures

Many mammalian cells can be grown in vitro (outside the body) under limited laboratory control. Several lines of cancer cells have been cultivated in a continuous culture for many decades. In the early stages of tissue culture technology, it was argued that certain chicken cells ( fibroblasts ) were maintained in culture for 20 years. This led to the idea that cells that are constantly dividing are potentially immortal, and interest in the study of aging was focused on differentiated (adult) cells. This view, however, later lost its position. . Today it is established that the fibroblast population ( clone ) has a limited life history in culture . It has a period of healthy growth, during which the culture can be “split”, several dozen times (that is, the cells go through several dozen divisions). After approximately 50th culture separation, however, they enter a phase of rapid degradation and die. Sometimes, chromosomes in cells give in to mutations that give cells the possibility of unlimited growth, creating a subpopulation that continues to grow after the 50th cleavage. This occurs much more frequently in mouse cells than in human cells. Such mutations usually leave chromosomal rearrangements or changes in the number of chromosomes.

Today, it is known that mammalian cells that are dividing with a normal chromosomal set have limited growth potential, and that the ability for unlimited growth, which is shown by cancer and transformed cells, is a result of the loss of a factor that limits growth. At the molecular level, during DNA replication , the polymerase is unable to replicate the ends of chromosomes. To avoid this limitation, there are several repeats of RNA - telomeres at the ends of the chromosomes, which, on the contrary, contract in somatic cells during each division. After the complete disappearance of telomeres in the cell, a program of apoptosis is initiated, programmed death. Stem and germ cells have the enzyme telomerase , which constantly replenishes telomeres, and it is mutations that activate telomerase, or mutations that interfere with the apoptosis program, and lead to the formation of "immortal" cells.

The limited potential for the division of senescent cells may be associated with a decrease in the rate of fibroblast metabolism and delayed wound healing with age.

Wear of non-renewable structures.

Another aspect of mammal aging is the wear and tear of certain organs that cannot be replaced. One of such systems is the chewing apparatus, in particular the jaws and teeth . Adapting to tooth wear rate is very important for animals, especially herbivores . Examples of such adaptations include the upper coronas (hypzodontia) of the teeth, a large surface area and a longer period of growth of the teeth. Wearing teeth can limit the lives of animals, as is sometimes the case with elephants , but in most cases this is not essential for survival. The same is true for other external wearing organs, such as, for example, the horns or lens of the eye . However, the deterioration of internal organs, such as cartilage of the joints, often leads to a decrease in the ability of animals to survive.

Immune system

An important system of the body, which suffers greatly during aging, is the immune system , part of which, the thymus- dependent subsystem, specializes in protecting against germs that enter the body, and some unhealthy cells of the body itself, which, due to changes, passed into them, are no longer recognized as part of the body, which leads to autoimmune reactions. Thus, the immune system is involved in protecting the body against cancer . Cancers are believed to be the result of single cells that can be transformed, either as a result of a genetic mutation, or as a result of the activation of a latent (dormant) virus (although there are other theories of cancer). It is the thymus-dependent immune subsystem that helps to stop the development of cancer.

It is known, for example, that immunosuppression procedures, which are usually carried out during organ transplantation , often lead to an increase in the number of tumors. The thymus-dependent subsystem can directly give rise to an older autoimmune disease, in which the immune system begins to perceive normal body tissue as foreign and begins producing antibodies against it. It is believed that the first step of this disease is a somatic mutation in one of the cells of the immune system.

The role of the immune system in aging is thus quite important, which even in the past led to the creation of several immune theories of aging, which tried to explain all the phenomena of aging in terms of mutations in the immune system.

Circulatory system

Changes in the circulatory system depend on the mammalian species, but are very pronounced in humans. The main physiological changes in the circulatory system are atrophy of the heart muscle, especially of the left ventricle, calcification of the heart valves, loss of vascular elasticity and deposition of inert materials in the vessels ( atherosclerosis ). The consequences of this are a decrease in blood flow and a slower response to temporary changes in blood demand, which leads to a decrease in oxygen supply , a decrease in the activity of the kidneys and liver, and an overall decrease in the supply of nutrients to body cells.

Nervous system

The loss of psychological and neurophysiological capabilities with age is undoubtedly a result of the loss of neurons , but changes in the metabolic processes of living cells are also involved in this process. The ability of the eye to adapt to darkness (that is, an increase in sensitivity at low light levels) decreases with age, but some of this decrease can be restored by inhaling pure oxygen. It is known that the mental abilities of older people are also improved by the inhalation of oxygen. The establishment of neural connections associated with memory requires protein synthesis , thus reducing protein synthesis by reducing oxygen consumption with age can be an important factor in weakening memory and learning abilities of older people.

Endocrine system

A common characteristic of endocrine system aging is the reduction of hormone production. However, it is not yet known exactly which processes are responsible for this decline. As a result of these changes, the body's reserves, sensitivity to environmental changes, stress and toxicity of chemicals decrease.

Skeletal system

In old age, the bones gradually lose calcium and become less strong. This can lead to osteoporosis and reduce the ability to withstand weight, increasing the likelihood of fractures. Thinning of the vertebrae also leads to a reduction in body height. In addition, the vertebrae harden, which leads to an increase in the stiffness of the entire spine and loss of maneuverability.

Joints are also amenable to change. In fact, arthritis is a common condition of the old age, which takes two general forms: osteoporosis (abrasion of the joint cartilage) and rheumatoid arthritis (connective tissue disease). These conditions can reduce the mobility and daily activity of the body.

• Aging (Biology)
• Hayflick's Limit
• Cell aging
• Participation Theory ^[1]
• Epigenetic regulation of aging
• DNA methylation

The main aspects of cultivation and transplantation of human fibroblast cultures

• Aging , Encyclopedia Britannica
• Physiology of aging , AgingPlace.org