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Models of aging in non-human primates

2021-03-11
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The human population has begun to continue to transform into an elderly population, which requires biomedical research to better understand the basic biology of aging and age-related diseases, and to promote new and improved treatment options. The breadth of carrying out this research is impractical, so animal models are needed to decompose the complexity of the aging process. The mouse model is the most commonly used choice, but the mouse model is not the most suitable model. At the same time, non-human primates are more closely related to humans, which outlines the human aging process and the development of age-related diseases. Extensive aging studies have been conducted in a well-characterized rhesus monkey aging model. , A life-threatening small non-human primate, is considered a potential model of aging. This model has special prospects as a disease model of aging, partly because of the successful creation of genetically modified marmosets. There are limitations to the use of non-human primates in aging research.

Keywords: non-human primate, animal model of aging, rhesus monkey, marmoset

Simulating human aging: Ideally, all biomedical research related to humans should be carried out in humans, but due to many physiological and technical considerations, this is obviously impractical. Therefore, it is necessary to model the human aging process in non-human systems. Many operations can be done without using animals, for example, by using computer models or in vitro systems. Although these systems are often useful, they cannot reproduce the complex and multifaceted physiological functions of aging in the body. Although many different non-human models are used to explore the aging process (e.g. yeast, roundworms, fruit flies, rats), mice are usually the model of choice.

Non-human primate aging research model: There are several obvious advantages in the dentate model, but the fundamental difference in the aging process between the dentate and the human is offset by the discovery of the dentate and directly translated into humans . Non-human primates are an important link between basic research and clinical applications, because the findings of non-human primates research can be highly translated into human health problems. The study of non-human primates provides an excellent trade-off between the limitations of the teeth and human studies. However, few studies have used non-human primate models of aging. This may be due to the challenges faced by the model, including the limited supply of aging animals, the need for specialized care, related use costs, and potential medical problems. Although there are several different types of primates used to simulate human aging, Old World monkeys, especially rhesus monkeys, have historically been the most studied. Recently, there has been growing interest in the use of a new small primate, the common marmoset, in aging research. First, we will focus on rhesus monkeys and marmosets.

Rhesus monkey musculoskeletal deterioration: physical weakness is a state of increased vulnerability with adverse health consequences; making the risk of disability, falls, hospitalization, and death higher. Rhesus monkeys are very useful for simulating age-related changes in the human musculoskeletal system, because they will develop muscle loss and bone loss during the aging process, which is a very serious condition for humans.

Muscle atrophy: It becomes more and more common with declining age, and matches the dynamics of muscle atrophy in rhesus monkeys with muscle weakness, disability, falls and fractures, as well as morbidity and mortality, and occurs in middle age, during which time increase. disappear slowly. It was observed that the decrease in the cross-sectional area of muscle fibers significantly resulted in muscle atrophy, and the increase in mitochondrial enzyme abnormal muscle fibers caused by mitochondrial DNA deletion mutations due to aging. Primates account for a higher proportion of the total body mass and are huge energy consumers.

Osteoporosis is a major health and economic problem worldwide. Osteoporosis is characterized by low bone mass, bone tissue degradation, bone structure destruction and bone strength degradation, all of which increase the risk of fractures. Although often used, it is not essentially an ideal model for human osteoporosis. Human leather bones reflect the continuous reshaping throughout life. Unlike humans, bone acquisition and vertical bone growth continue after sexual maturity in mice. In many strains, bone growth continues into old age. Experience true menopause. Although they may experience irregular cycles at 10 months of age, estrogen levels remain the same, and uterine weight (an indicator of functional estrogen exposure) remains at normal levels until old age. Similarly, male mice maintain testosterone levels as they age. Conversely, rhesus monkeys and other old world monkeys are excellent models of human osteoporosis because they have bone remodeling of cortical bone. , And similar reproductive endocrine systems that affect bone metabolism. After the bone mass of about 10 years old reaches the front end, the rhesus monkey reliably increases bone renewal and bone loss through age and natural or surgically induced estrogen depletion.

Non-human primates (such as rhesus monkeys) provide a special case for studying naturally occurring osteoarthritis.

Rhesus monkey menopause: Menopause can be defined as the natural result of the aging process of human females gradually disappearing to restore reproductive ability. This loss of reproductive capacity includes the complete cessation of ovulation and menstruation, and is accompanied by the function and structure of the hypothalamus-pituitary-ovarian axis. In addition, there are variables directly related to menopause, and changes in the hormonal environment related to menopausal status also mean an increased risk of age-related diseases and complications (including musculoskeletal and vascular) diseases. Globally, it has recently been established that there is a positive correlation between menopause and epigenetic aging in the blood. Monkeys are widely used in biomedical research and are classified with other non-human primates. The reproductive aging of this species has more comprehensive characteristics.

Rhesus monkey speed limitation (CR): A major challenge in aging research comes from the biological complexity of the aging process itself. More than 80 years ago, a seemingly simple method of reducing replacement was proven to slow down the aging of dental animals. Since then, continuous reduction of repeated attacks without malnutrition has been proven to be the most effective and long-lasting intervention. It can delay the aging of different species and is the only environmental intervention. The rhesus monkey is a good model of musculoskeletal aging. For a long time, bone and muscle health has been a restricted (CR) area of concern. In human and non-human primate models, short-term (<1 year) CR has been reported to reduce physical activity and metabolic rate. Long-term CR reduces the basal metabolic rate, but maintains higher physical activity and reduced exercise metabolic costs. Animals that adhere to CR appear to be biologically younger than normal replacement animals.

New World Monkey Aging Model: Among the New World monkeys, common marmosets are the most promising for aging research. Researchers are actively seeking new technologies (such as CRISPR) to create genetically modified marmosets that target diseases. This makes marmosets a particularly attractive model for neurodegenerative diseases such as Parkinson’s disease. Short life span and fast life history. The changed time course can reduce the risk of lack of control of research variables (including the exchange of equipment and personnel) during the aging research process. Lihe litter is a hematopoietic interventional body. This complication provides several potential benefits, including the ability to limit and variability between experimental groups, and the opportunity to study the impact of early environments on later life outcomes. Unlike rhesus monkeys, marmosets do not have any zoonotic diseases that humans are particularly concerned about.

Common neurodegenerative disease models of marmoset monkeys: Marmosets, due to their small size, similarity to the human brain, and a combination of proven behavior, surgery and imaging techniques, include Parkinson’s disease and Alzheimer’s disease These similarities include evidence of decreased age-related neurogenesis that occurs before aging. The model is particularly useful, and a genetic model of Parkinson’s disease has recently been developed.

Aging intervention of marmoset monkeys: 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 regulating this process. Rapamycin was originally proven to extend the lifespan of yeast cells, but it was later shown to extend the lifespan of nematodes, flies, mice and human cells, even in rapamycin-treated elderly mice. Research is currently being conducted on marmosets to determine the impact of rapamycin on the life of non-human primates. These studies prove that the marmoset is an excellent model for studying long-term continuous intervention.

This work has great value, but non-human primates provide a combination of easy-to-handle models that are very close to human anatomy. Ideally, age-related diseases and conditions will be modeled in the elderly. In order to replicate the aggravating environment that exists in human conditions. With development, the practicability of the marmoset aging model will be improved, and the value of the genetically modified marmoset will be fully realized.

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