Current location - Education and Training Encyclopedia - Graduation thesis - Comparative study on aging
Comparative study on aging
Because of the short life span of invertebrates, when used to study aging, the experimental period is short and easy to repeat. Although invertebrates are very different from vertebrates in appearance, they have many similarities at the cellular level. Some people compared the changes of cell senescence in Drosophila and mice, and found that the changes of various organelles were very similar. Such as nuclear depression, mitochondrial enlargement, ribosome reduction and so on. If further analyzed at the molecular level, many biochemical processes in invertebrate or vertebrate cells are basically the same. Therefore, rotifers, nematodes, fruit flies and houseflies are often used as materials to study aging. Comparing invertebrates with vertebrates, it is found that many factors such as heredity, reproduction, temperature and food are closely related to aging.

Animals with different genetics and aging have their own specific life limits. For example, the adult life span of Mayflies is only one day, while the adult life span of fruit flies and houseflies can exceed 30 days. One nematode can live for 28 days, and the other parasitic nematode can live for 17 years. European lobsters can live up to 30 years. The lifespan of mammals also varies greatly. Mice and rats need about 3 years, elephants need 70 years, and humans need 1 10 years. In the population survey, it is very common for long-lived families to have long-lived offspring. The life span of monozygotic twins is very close, while the life span of monozygotic twins may be very different. All these prove that heredity plays a leading role in life span.

The life expectancy of human women is often longer than that of men, which is usually attributed to social factors, that is, women bear less pressure on life. In fact, in addition to the external factors such as men's high work and labor consumption and many opportunities for injury, gender also has an impact on life expectancy. Sex is determined by sex chromosomes. Women are XX type and men are XY type. Many genetic diseases are located on the X chromosome. In women, it is not pathological because it covers up another X chromosome, but in men, it is not. Heredity determines the sex of men and women, and also causes the difference in life expectancy.

Another phenomenon in the animal kingdom is that female animals live longer than male animals (see picture). 17 days, the mortality rate of male flies was 50%, and the mortality rate of female flies reached 50% in 32 days. In addition, the average life span of a black spider is 100 days for males and 27 1 day for females. The average life span of Daphnia magna is 38 days for males and 44 days for females.

Reproductive and aging organisms rely on reproduction to maintain the continuation of the population. Reproductive mode has an important influence on the aging of the body. Creatures that reproduce once will soon age and then die. Many insects and a few vertebrates, such as several kinds of salmon in the Pacific Ocean, belong to the primary breeding type. Creatures that reproduce repeatedly can reproduce repeatedly in their lifetime. Most vertebrates and longevity insects belong to the type of multiple reproduction.

Many insects have two obviously different adaptive colors, one is protective color and the other is warning color. Animals with protective colors die shortly after the end of reproductive period; Insects with warning colors survive longer after reproduction. If insects fly much after reproduction, they will consume a lot of energy stored in their bodies and die soon. Less flying insects can save energy and maintain a longer life. Insects that reproduce once actually need to maintain all their functions and vitality until the end of their lives, and aging only occurs in a short time after the completion of the reproduction process.

Vertebrate salmon is also a kind of reproductive animal, which will age and die immediately after spawning. Some people have used castration to prevent spawning and avoid degeneration after spawning, so the life span of fish can be extended for several years, so it is considered that the maturity of reproductive organs contains aging factors. Oviposition itself can cause endocrine changes, but it is not the direct cause of death.

Mammals belong to many reproductive types. The following table shows some information about pregnancy, maturity, growth period and life span of mammals. Early maturity, strong reproductive ability, more litters at one time, and shorter life span of animals with multiple litters a year.

Small rodents such as rats, mice and guinea pigs are such examples. However, large animals, such as cattle, horses, elephants and people, have long growth period, long pregnancy period, low birth rate and long life span.

From the perspective of comparative gerontology, the metabolism of many cold-blooded animals is affected by external temperature, which can lower body temperature and prolong life. For example, some reptiles and amphibians live in the tropics and have a short life span, while those living in lower temperature zones have a longer life span. Some people raise annual fish from South America at 15℃ and 26℃. As a result, the group with low temperature grew fast, grew big and lived long. It shows that cold-blooded animals can adapt to the changing temperature environment and prolong their life at low temperature.

Warm-blooded animals can keep their body temperature constant and their metabolic rate is relatively stable. For example, bats can often sleep for a day and their metabolism is slow. During hibernation, the body temperature drops, and the life span can reach 15 ~ 17 years. In the case of active action and rapid metabolism, mice can't lower their body temperature to adapt to the environment, and their life span is only 3 years. If young rats are kept at low temperature, they will not prolong their life, but will be prone to diseases and shorten their life.

The intake of food and life can directly or indirectly affect the disease resistance of animals, thus affecting their life span. Some people feed weaned male rats with limited food to make them live longer than those who eat at will. However, another experiment shows that if rats get enough food before 120 days, their life span will be longer than that of animals with food restriction. The maturity of rats is 120 days, which shows that if enough food is given during the growing period, the physique can be enhanced and the average life expectancy can be prolonged. Some people think that food is related to weight and longevity.

Some people have done a series of nutrition experiments with houseflies, cockroaches and worker bees. It is believed that food affects the oviposition time of insects and indirectly affects their life span.

Changes in aging period The aging of the body has certain changes from macro to micro, and it is more and more obvious with the growth of age. Although some people have studied the aging changes of lower animals, the number is limited, and most of them are used to establish some aging models and carry out anti-aging experiments, so the data about their aging changes are scattered and lack of systematicness. More information has been accumulated about the aging changes of human beings and mammals.

Generally speaking, the height of the elderly is reduced, the spine is bent, the skin loses elasticity, facial wrinkles are increased, and pigmentation and brown spots of different sizes can be seen on local skin, especially on the face and hands, which are called senile spots. The secretion of sweat glands and sebaceous glands decreases, making the skin dry and dull. Gray hair, alopecia or even baldness, drooping eyelids, and a whole or half circle of white narrow band around the cornea, which is called senile ring (or senile arch), is caused by lipid deposition.

Teeth fall off, but the time varies from person to person. In terms of behavior, the elderly are slow to respond, walk slowly, gradually dull facial expressions, poor memory, inattention and frequent language repetition. Vision loss and hyperopia tendency. Hearing is also prone to degradation. The above situation varies greatly from person to person. For example, baldness does not necessarily lead to tooth loss, and people with wrinkles may also be refreshed.

The aging changes of tissues and organs at the whole level are based on the aging changes of tissues and organs.

With the increase of age, the bone tissue of the skeletal system gradually decreases calcium, and the bones become brittle and easy to fracture, and the wound healing is slower than that of young people. The range of motion of joints is decreased, and it is easy to suffer from arthritis. Fibrocartilage pad between vertebral bodies of the spine is thinned due to cartilage atrophy, which leads to the shortening of the spine, which is also a reason for the shortening of the elderly.

The dermal papilla of aging skin becomes lower, which makes the interface between epidermis and dermis flat, epidermis thinner, dermal reticular fibers decrease, elastic fibers gradually become inelastic and easy to break, collagen fibers update slowly, and old fibers are mostly. The increase of collagen crosslinking reduces the elasticity of collagen fiber network. The skin is flabby, no longer attached to subcutaneous structures, hyaluronic acid in intercellular substance is reduced, chondroitin sulfate is relatively increased, so that the water content of dermis is reduced, subcutaneous fat, sweat glands and sebaceous glands are atrophied, and local melanocytes proliferate and senile plaques appear.

Muscle in the elderly, the ratio of muscle weight to body weight decreases. Water, sodium and chlorine outside muscle cells tend to increase, while potassium content inside cells tends to decrease. In addition, the number of muscle fibers decreases and the diameter becomes smaller, which makes the whole muscle atrophy. This aging change varies with different functions. Contraction time tends to be prolonged in different fast-contracting muscles or mixed muscles, but shortened in slow-contracting muscles, which will affect the interaction of different sports units and reduce the effectiveness of muscle group coordination, which is probably one of the reasons for muscle weakness in the elderly. Of course, the aging of motor units is not enough to explain all the motor disorders of the elderly, because the complex mechanisms at different levels of the nervous system will have an impact on exercise.

When the nervous system is 90 years old, the weight of the human brain is lighter than that at the age of 20 10 ~ 20%. The main reason for weight loss is the loss of nerve cells. This loss is region-specific, for example, the degree of cell reduction in different regions of the brain is different. From birth to 10 years old, nerve cells have proliferated to the maximum and no longer divide, and cells begin to lose after 20 years old. However, the whole brain cell base is very large, and the death of some cells will not cause serious dysfunction. Moreover, people don't know much about the mechanism of memory, so memory loss may not be caused by cell loss.

From the general anatomy, the posterior meninges of the elderly are thickened, the gyrus is narrowed, the sulcus is wide and deep, and the ventricular cavity is enlarged. Microscopically, Nissl bodies in nerve cells decreased and lipofuscin was deposited. Functionally, nerve conduction speed slows down, short-term memory is worse than long-term memory, and physiological sleep time is shortened; Sensory functions such as temperature, touch and vibration all decrease, taste threshold increases, and audio-visual sensitivity decreases. The reaction ability is generally reduced, especially in the case of choice and decision.

The cardiac capacity of the elderly in the cardiovascular system is increasing. There is no evidence that lipofuscin deposition has any adverse effects on myocardial function. In the cardiac conduction system, the number of pacing cells decreases, while the fibrous tissue in sinoatrial node and internodal bundle increases. On the arterial side, the intima also thickens to varying degrees, which may lead to stenosis of arteriole lumen. After the age of 30, the intima of coronary artery branches began to thicken, and the intima became increasingly fibrotic, and some smooth muscles might be necrotic. The most prominent aging change was delamination of elastic fiberboard? 6. Arterial vascular degeneration, increased peripheral vascular resistance and increased arterial pressure.

The costal cartilage in the elderly may be calcified in the respiratory system, and the hunchback will increase, which will lead to the expansion of the anterior and posterior diameter of the thoracic cavity into a "barrel chest". Microscopically, alveolar ducts and respiratory bronchioles are enlarged, which reduces the volume of surrounding alveoli.

Generally speaking, the aging changes of digestive system are not significant, and tooth loss is related to the protection of teeth, which is not necessarily a feature of aging. Microscopically, the acid-secreting cells in the stomach decrease with the increase of age, and the number of cells per unit volume of liver tissue also decreases. Lymphatic aggregation in the small intestine is most obvious when young. In old age, the weight loss of human and rat kidneys reaches 20-30%, and the number of glomeruli decreases. At the age of 40, normal glomeruli accounted for 95%, and at the age of 90, only 63% remained. The length and volume of proximal convoluted tubule decrease. With the increase of age, the basement membrane thickens and the interstitial tissue of medulla increases. Functionally, glomerular filtration rate decreases, and the following formula can be obtained by calculating inulin clearance rate (c):

C inulin (ml/min) = 153.2-0.96× age

From the age of 20 to 70, the renal blood flow velocity decreased by 53%. If the maximum output of p-aminohippuric acid (TMPAH) is calculated, the renal tubular function will decrease with age, as shown below:

TMPAH (mg/min) = 120.6-0.865× age

In addition, the elderly over 65 years old have nocturia, urgency and incontinence to varying degrees.

The gonadal atrophy of endocrine system is the most obvious aging change of endocrine system. For example, when women stop menstruating at the age of 45-50, the secretion of estrogen drops obviously, and when men are at the age of 50-90, the androgen gradually decreases, leading to sexual dysfunction. Accordingly, various atrophic changes in reproductive and accessory organs, such as hormones formed by ovarian lymphocytes, all lead to decreased immune function.

Because of the complexity of each organ and the interaction between endocrine organs, the cellular level can be expounded from two aspects: in vivo cells and in vitro cells.

The aging cells in the body are mainly fixed splinter cell, which stops dividing soon after birth and cannot be replenished after death, such as nerve cells and myocardial cells. When the body is aging, the structure and composition of these cells change to varying degrees, such as the decrease of cell number (due to local cell death), the decrease of mitochondrial crista and matrix, the expansion of volume, and even the destruction and disappearance. Under the optical microscope, the rough endoplasmic reticulum of nerve cells lost its typical structure and Nissl bodies decreased. The aging changes of the nucleus are characterized by the weakening of Vergen staining positive substances and the invagination of the nuclear membrane to form folds. The prominent change in old age is the accumulation of lipofuscin in myocardial cells mentioned above. With the increase of age, the accumulation in nerve cells can account for more than half of the extranuclear volume. Lipfuscin is brown and granular, with spontaneous fluorescence. Under the electron microscope, it can be seen that it is surrounded by a single-layer film, which contains electron-dense substances, sometimes with transparent areas or layered structures. The rate of its growth with age varies with different cells and animals, and the effect of accumulation on cell function is still a controversial issue.

With the increase of culture generations, the aging of cells in vitro is characterized by intracellular changes. Since L. hayflick discovered the life span of diploid human embryonic lung fibroblasts in 196 1 year, a great deal of data about cell senescence in vitro have been accumulated. When the cell proliferation reaches a dense monolayer, it must be subcultured in a bottle. If 1 is divided into two, the number of passages is only 50 10, which is the limit of doubling the cell population, that is, the life span of cultured cells. This figure is related to the age and species of the donor. Older donors have fewer generations of cell culture than younger donors. Long-lived donors also have more cell culture generations than short-lived donors. After 30 ~ 40 generations of culture, fluorescent particles appeared in the cells, nucleoprotein particle RNA decreased, and mitochondria lacking cristae increased. These are all age changes. The changes of many parameters have also been measured in biochemistry. Therefore, many researchers at home and abroad regard these cells as aging models. In addition to fibroblasts, cell lines such as endothelial tissue, lymphocytes and smooth muscle cells have been established, and these cell lines have a certain culture life limit.

The aging of uterus and cells at the molecular level is ultimately related to the aging at the molecular level. First of all, as far as extracellular molecules are concerned, extracellular connective tissue and basement membrane have specific aging changes. Connective tissue is rich in collagen and elastin. With the increase of age, cross-linking bonds are formed between collagen molecules. 30 ~ 50 years old is the period of rapid increase of crosslinking. With the increase of crosslinking degree, the water absorption of collagen fiber decreases, and it loses its toughness and tends to be stiff, which is not conducive to tissue activities. Elastin is the main component of elastic fiber, and it will also cross-link during aging. The fiber is broken and brittle, and the appearance is yellow and deepened. As for the basement membrane, it is only known that it thickens during aging, and the main component is collagen, followed by glycoprotein and carbohydrate. However, it is not clear how these molecules change and cause membrane thickening. In addition, as extracellular substances, of course, there are blood and lymph. These substances are often in operation and constantly updated, so it is difficult to determine the aging index.

Secondly, as far as the aging of intracellular molecules is concerned, the substantial aging changes of some constantly updated intracellular molecules, such as enzymes in metabolic reactions, are still rare. But its renewal speed-synthesis and degradation speed-may slow down with age. Whether its biological activity increases or decreases depends on different enzymes. Other molecules that do not update after synthesis, such as deoxyribonucleic acid (DNA) during cell division, do not degrade after synthesis. Some people think that the molecular weight of DNA molecules decreases with age, which may be caused by the increase of breaks. The number of DNA base pairs arranged repeatedly on nucleosomes in the elderly is more than that in the young. The combination of DNA and histone increased, and the ratio of histone to non-histone in chromatin increased. As for the ability of aging individuals to repair DNA damage, people don't know much, but most of them take isolated cells as the research object, and think that DNA repair ability decreases with the increase of culture generation age, which seems to be positively related to the donor life of cultured cells, that is, the cells of long-lived animals have high repair ability in culture.

In addition to DNA, the content of macromolecules in cells, such as crystallin in lens fibers of eyeball, increases with age. Soluble proteins in human crystals predominate before the age of 50, and decrease after the age of 50, while insoluble or insoluble proteins and their molecular weights increase with age, especially in the center of the crystal, indicating that soluble proteins synthesized in the early stage polymerize with age to form polymers with larger molecular weights.

People's understanding of aging at the molecular level is limited, and the research results are often contradictory, which needs further discussion on the basis of technical improvement.