动物衰老模型 z-bo 2020-07-23 751

　　Simulating human aging: Ideally, all biomedical research related to humans should be conducted in humans, but due to many ethical and technical considerations, this is obviously unrealistic. Therefore, it is necessary to model human aging in non-human systems. Many operations can be performed without animals, including the use of computer models and in vitro systems. Although these systems are often useful, they cannot replicate the complex and multifaceted physiological functions of aging. Although many different non-human models (yeast, roundworm, fruit flies, rats, etc.) are used to study the aging process, the mouse is usually the best model. Non-human primate aging research model: The rodent model has obvious advantages, but the fundamental difference in the aging process between rodents and humans directly translates the findings of rodents into humans. On the other hand, non-human spirits Long animals are an important link between basic research and clinical applications. The findings of non-human primate studies are due to their high translation into human health problems. Non-human primates are ideal translation models because they have surprisingly similar genetic, physiological and behavioral characteristics to humans. The study of non-human primates provides an excellent compromise between the limits of rodent and human research. However, few studies have used non-human primate models of aging. This may be due to the challenges faced by the model, such as the limited supply of elderly animals, the need for special care, the high cost of use, and potential ethical issues. may. Although several different types of primates can be used to simulate human aging, historically, monkeys in the old world, especially rhesus monkeys, have been the most in-depth research. Recently, in aging research, there is growing interest in the use of new little primates, ordinary monkeys. The following focuses on rhesus monkeys and marmosets. \r\nMusculoskeletal aging in Rhesus monkeys: Fragility is a fragile and unhealthy condition that increases the risk of disability, falls, hospitalization and death. The prevalence of frailty increases with age. As we age, the degeneration of the musculoskeletal system can lead to physical weakness. Rhesus monkeys cause muscle and bone loss during aging. It is a very common human disease and is very useful for simulating age-related changes in the human musculoskeletal system. \r\nMuscular dystrophy: Muscular dystrophy refers to the decrease in the number of skeletal muscles that work with age. As we age, muscle wasting becomes more common and is associated with muscle weakness, disability, falls, fractures, and increased morbidity and mortality. The rhesus monkey is the best model of human muscle wasting. Unlike rodents, rodents will experience significant muscle atrophy later in life.

　　 The dynamics of muscle atrophy in rhesus monkeys is consistent with that of humans, and it gradually develops and disappears in middle age. The reduced cross-sectional area of muscle fibers significantly leads to muscle waste, and with age, mitochondrial DNA deletion mutations lead to an increase in mitochondrial enzyme abnormal muscle fibers. In addition, compared with rodents, skeletal muscle accounts for a higher proportion of the total weight of primates and consumes more energy. \r\nOsteoporosis: Osteoporosis is a major health and economic problem in the world. Osteoporosis is characterized by bone loss, bone tissue degradation, bone structure destruction and bone strength loss, all of which increase the risk of fractures. Mice are often used, but they are not an ideal model for human osteoporosis. The human cortical bone reflects the continuous reshaping of the entire life. Mouse cortical bone rarely undergoes Haversian remodeling. The cortex is mainly composed of ring-shaped flakes, which are formed on the outer surface as the bone grows.

　　 Unlike humans, the acquisition of bones and the longitudinal growth of bones continue after the sexual maturity of mice. In many strains, bone growth will continue to age. In addition, the mice did not experience true menopause. Although they may experience irregular cycles at 10 months of age, estrogen levels remain the same, but uterine weight (an indicator of functional estrogen exposure) remains normal until old age. Similarly, male mice will maintain testosterone levels as they age. On the other hand, rhesus monkeys and other larger monkeys are excellent models of human osteoporosis, because they have a similar reproductive endocrine system that affects bone remodeling and cortical bone bone metabolism. After approximately 10 years of peak bone mass, rhesus monkeys, through natural or surgically induced estrogen consumption, reliably increase bone regeneration and bone loss with age. This is not surprising, because they are very similar to humans in the menstrual cycle, the development of natural menopause, and the bone remodeling of cancellous and cortical bone. \r\nOsteoarthritis: Osteoarthritis has the highest incidence of any type of arthritis in the world and is the main cause of chronic pain diseases. Non-human primates (such as rhesus monkeys) provide a special case for studying naturally occurring osteoarthritis. Menopause in monkeys: Menopause can be defined as the natural result of the aging process, during which women gradually lose their fertility. This loss of fertility includes complete cessation of ovulation and menstruation, and changes in the function and structure of the hypothalamic-pituitary-ovarian axis. The importance of studying menopausal diseases in model species cannot be underestimated. Not only are there adverse effects directly related to menopause, but the hormonal environmental changes associated with menopause also increase the risk of age-related diseases and conditions, including musculoskeletal and cardiovascular diseases. I mean. .. Globally, it has recently been established that there is a positive correlation between menopause and epigenetic aging of the blood. Rhesus monkeys after menopause mimic human physiology. Compared with other non-human primates, in view of the wide application of rhesus monkeys in biomedical research, this reproductive and senescent species has more comprehensive characteristics. \r\nJesus calorie restriction (CR): The main challenge in aging research is the biological complexity of the aging process itself. More than eighty years ago, it was proven to slow down rodent aging and the onset of age-related diseases in a seemingly simple way of reducing calorie intake. Since then, the continuous reduction of malnutrition and the reduction of caloric intake have been shown to delay the aging of various species, and is the most effective and long-lasting intervention for laboratory rats. .. This is the only environmental intervention that can be expanded. Delay maximum life span and biological aging. Rhesus monkeys are a good model of musculoskeletal aging. For a long time, bone and muscle health has been a concern for calorie restriction (CR). According to reports, short-term (one year) CR may reduce physical activity and metabolic rate in human and non-human primate models. Long-term CR may reduce the basal metabolic rate, but it can maintain higher physical activity and lower exercise metabolic costs. Animals attached to CR are biologically younger than normally fed animals. \r\nAging model of New World monkeys: Among the New World monkeys, ordinary marmosets are the most promising aging research. Similar to macaques, common marmosets share approximately 93% sequence homology with the human genome, causing similar human-related diseases and disorders, such as diabetes, cardiovascular disease, and cancer. The mos monkey is considered a model for neuroscience, infectious diseases, behavioral research, obesity and reproductive biology. Researchers are actively seeking new technologies (such as CRISPR) to create genetically engineered marmosets that target diseases. This makes marmosets a particularly attractive model for neurodegenerative diseases such as Parkinson's disease. Compared with rhesus monkeys, one of the main benefits of March monkeys is their short life span and fast life span. Shortening the time course can reduce the risk of uncontrollable research variables (including equipment and personnel availability) during the aging research process. The second major advantage of the monkey model is its high fertility and litter-mediated hematopoietic chimerism. This chimera has several potential advantages, including the ability to limit variation between the control and experimental groups, and the opportunity to study the effects of early environments on later results. Other advantages are smaller than monkeys, generally easier to operate and maintain, and have less space for movement. Unlike rhesus monkeys, marmosets have no particular concern for zoonotic diseases. \r\n Marmoset's general neurodegenerative disease model: Marmosets are small, similar to the human brain, and their behavior includes Parkinson’s disease, Alzheimer’s disease, surgery and diagnostic imaging techniques (including severe diseases, Huntington’s disease) ). The confirmed diseases are epidemiological models of various neurodegenerative diseases (such as sclerosis). These similarities include evidence of decreased age-related neurogenesis that occurs before aging. Lichen monkeys are particularly useful as a neurotoxin induction model for Parkinson's disease, and a genetic model for Parkinson's disease has recently been developed. \r\n Marmoset aging intervention: A large amount of evidence confirms that maintaining the balance of cell protein is one of the key processes to ensure longevity. People are increasingly aware of the role of rapamycin (mTOR) mechanism targets in controlling this process. Rapamycin (rapamycin) is an mTOR inhibitor used in human immunosuppressive therapy after transplantation. Rapamycin was originally shown to extend the lifespan of yeast cells, and later proved to have a beneficial effect on the lifespan of nematodes, fruit flies, mice and human cells. We also found that rapamycin-treated elderly mice can also prolong lifespan. Monkeys are currently being studied to determine the effect of rapamycin on the lifespan of non-human primates. Further studies have shown that rapamycin can induce monkey tissues to specifically up-regulate certain components that regulate protein homeostasis. These studies show that marmosets are an excellent model for studying long-term aging interventions. \r\nConclusion: Most research on aging has focused on non-primates. Although very valuable for this research, non-human primates provide a manageable combination of models that are very close to human anatomy, physiology and behavior, and their development and age are similar to humans.

　　Ideally, aging-related diseases and conditions are studied in an aging model that simulates the aging environment that exists in human conditions. The further development of research methods and resources will improve the practicability of monkey aging models and fully realize the value of genetically modified marmosets. \r\nhuman simulates human aging: Ideally, all biomedical research related to humans should be carried out in humans, but this is obviously due to many ethical and technical considerations. unrealistic. Therefore, it is necessary to model the human aging process in non-human systems. Many operations can be performed without animals, such as using computer models or in vitro systems. Although these systems are often useful, they cannot replicate the complex and multifaceted physiological functions of aging. Although many different non-human models are used to study the aging process (e.g. yeast, roundworm, fruit flies, rats), mice are usually the model of choice. Research models of aging in non-human primates: Rodent models have some obvious advantages, but the fundamental differences in the aging process between rodents and humans directly translate rodent discoveries into humans. In order to prevent being on the other hand, non-human primates are an important link between basic research and clinical applications. The findings of non-human primate studies are due to their high translation into human health problems. Non-human primates are ideal translation models because they have surprisingly similar genetic, physiological and behavioral characteristics to humans. Research on non-human primates provides an excellent compromise between the limitations of rodent and human research. However, few studies have used non-human primate models of aging. This may be due to the challenges faced by the model, such as the limited supply of elderly animals, the need for specialized care, the high cost of use and potential ethical issues. possible. There are several different types of primates that can be used to simulate human aging, but historically, monkeys in the Old World, especially rhesus monkeys, have been the most studied. Recently, there has been a growing interest in using new little primates, common, monkeys in aging research. The following focuses on rhesus monkeys and marmosets.

　　 Rhesus musculoskeletal aging: Fragility is a fragile and unhealthy condition that increases the risk of disability, falls, hospitalization, and death. The prevalence of frailty increases with age. As we age, the degeneration of the musculoskeletal system can lead to weakness. Rhesus monkeys can cause muscle loss and bone loss during aging, which makes it a very common disease in humans, which is very useful for simulating age-related changes in the human musculoskeletal system.

　　 Muscle atrophy: Muscle atrophy is the loss of skeletal muscle mass and function with age. As we age, muscle wasting becomes more common and is associated with muscle weakness, disability, falls and fractures, as well as increased morbidity and mortality. The rhesus monkey is the best model of human muscle wasting. Unlike rodents, rodents experience significant muscle atrophy in their later years. The dynamics of muscle atrophy in rhesus monkeys is consistent with that of humans, and it develops and gradually disappears in middle age. The reduction in the cross-sectional area of muscle fibers significantly causes muscle atrophy, and with age, mitochondrial DNA deletion mutations lead to an increase in mitochondrial enzyme abnormal muscle fibers. In addition, compared with rodents, skeletal muscle accounts for a higher proportion of the total weight of primates and is a huge energy consumer.

　　 Osteoporosis: Osteoporosis is a major health and economic problem worldwide. Osteoporosis is characterized by bone loss, bone tissue degradation, bone structure destruction and bone strength loss, all of which increase the risk of fractures. Mice are often used, but they are not an ideal model for human osteoporosis. The human cortical bone reflects the continuous reshaping of the entire life. Mouse cortical bone rarely undergoes Haversian remodeling. The cortex is mainly composed of annular sheets formed on the outer surface as the bones grow. Unlike humans, the acquisition of bones and the longitudinal growth of bones continue after the sexual maturity of mice. In many strains, bone growth continues into old age. Moreover, the mice did not experience true menopause. Although they may experience irregular cycles at 10 months of age, estrogen levels remain the same, while uterine weight (an indicator of functional estrogen exposure) remains normal until old age. Similarly, male mice will maintain testosterone levels as they age. On the other hand, rhesus monkeys and other older monkeys are excellent models of human osteoporosis because they have similar reproductive endocrine systems that affect bone remodeling and cortical bone bone metabolism. After about 10 years of peak bone mass, rhesus monkeys will reliably increase bone regeneration and bone loss with age, either naturally or through surgically induced consumption of estrogen. This is not surprising, because they are very similar to humans during the menstrual cycle, the development of natural menopause, and the bone remodeling of cancellous and cortical bone.

　　 Osteoarthritis: Osteoarthritis has the highest incidence of any type of arthritis in the world and is the main cause of chronic painful diseases. Non-human primates (such as rhesus monkeys) provide a special case for studying naturally occurring osteoarthritis. Monkey menopause: Menopause can be defined as the natural result of the aging process in which human females gradually lose their fertility. This loss of fertility includes complete cessation of ovulation and menstruation, as well as changes in the function and structure of the hypothalamic-pituitary-ovarian axis. The importance of studying menopausal diseases in model species cannot be underestimated. Not only are there adverse effects directly related to menopause, but the hormonal environmental changes related to menopausal status also mean an increased risk of age-related diseases and disorders (including musculoskeletal and cardiovascular diseases). .. Globally, it has recently been established that there is a positive correlation between menopause and epigenetic aging of the blood. Rhesus monkeys have gone through menopause and imitated human physiology. In view of the wide application of rhesus monkeys in biomedical research, compared with other non-human primates, this reproductive and aging species has more comprehensive characteristics.

　　Hesus calorie restriction (CR): The main challenge in aging research comes from the biological complexity of the aging process itself. More than eighty years ago, it was proven to slow down rodent aging and the development of age-related diseases in a seemingly simple way of reducing calorie intake. Since then, continuous reduction of caloric intake without malnutrition has proven to be the most effective and long-lasting intervention that can delay the aging of different species and is effective in experimental rats. And it is the only environmental intervention that can be expanded. Delay maximum life span and biological aging. Rhesus monkeys are a good model of musculoskeletal aging. For a long time, bone and muscle health has been a concern for calorie restriction (CR). According to reports, short-term (\u003c1 years) CR can reduce physical activity and metabolic rate in human and non-human primate models. Long-term CR can reduce the basal metabolic rate, but can maintain higher physical activity and lower exercise metabolic costs. Animals attached to CR are biologically younger than normally fed animals.

　　The aging model of the New World Monkey: Among the New World monkeys, the common marmoset is the most promising research on aging. Similar to rhesus monkeys, common marmosets share about 93% sequence homology with the human genome, and cause similar human-related diseases and disorders, such as diabetes, cardiovascular disease and cancer. The mos monkey is a recognized model for neuroscience, infectious diseases, behavioral research, obesity and reproductive biology. Researchers are actively seeking new technologies (such as CRISPR) to create genetically engineered marmosets that target diseases. This makes marmosets a particularly attractive model for neurodegenerative diseases such as Parkinson's disease. One of the main advantages of mar monkeys over rhesus monkeys is their short life span and fast life span. By reducing the time course, you can reduce the risk of not being able to control research variables (including equipment and personnel availability) during the aging study. The second major advantage of the mo monkey model is its high fertility and litter-mediated hematopoietic chimerism. This chimera has several potential advantages, including the ability to limit variation between the control and experimental groups, and the opportunity to study the effects of early environments on late life outcomes. Other advantages are that they are smaller than macaques, are generally easier to handle and maintain, and have less space to move. Unlike rhesus monkeys, marmosets do not have zoonotic diseases of particular concern.

Marmoset's general neurodegenerative disease model: Marmosset is small, similar to the human brain, and has proven behaviors such as Parkinson's disease, Alzheimer's disease, surgery and imaging technology, including Harsh disease, Huntington Disease, an epidemiological model of a variety of neurodegenerative diseases (such as sclerosis). These similarities include evidence of decreased age-related neurogenesis that occurs before aging. The mos monkey is particularly useful as a neurotoxin induction model for Parkinson's disease, and a genetic model for Parkinson's disease has recently been developed.

　　Marmoset's aging intervention: A large amount of evidence supports that maintaining cell protein balance is one of the key processes to ensure longevity. People are increasingly aware of the role of rapamycin (mTOR) mechanism targets in controlling this process. Rapamycin (Rapamycin) is an mTOR inhibitor used in human immunosuppressive therapy after transplantation. Rapamycin was originally shown to extend the lifespan of yeast cells, and later proved to have a beneficial effect on the lifespan of nematodes, fruit flies, mice and human cells. We also found that rapamycin-treated elderly mice can also prolong lifespan. Monkeys are currently being studied to determine the effect of rapamycin on the lifespan of non-human primates. Further studies have shown that rapamycin induces mar monkey tissue to specifically up-regulate certain components that regulate protein homeostasis. These studies show that marmosets are excellent models for studying long-term aging interventions.

　　 Conclusion: Most research on aging has focused on non-primates. Although very valuable for this work, non-human primates provide a manageable combination of models that are very close to human anatomy, physiology and behavior, and their development and age are similar to humans. Ideally, age-related diseases and conditions are studied in an aging model that simulates the aging environment that exists in human conditions. The further development of research methods and resources will improve the practicality of the monkey aging model and fully realize the value of genetically modified marmosets.