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Rejuvenation new ideas: activate stem cells

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2018/09/28 14:20
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Longevity has not only been a human dream, but anti-aging has also been a hot spot in biological research. Nowadays, among the anti-aging methods, it is recognized that the most likely effects are calorie restriction, resveratrol, metformin, and rapamycin. Among them, metformin should be widely used by humans because it is the most A wide range of diabetes drugs, with good results and small side effects, personally believe that metformin is the anti-aging drug most likely to be routinely used. Other means such as caloric restriction and rapamycin are unlikely to be long-term clinical studies due to side effects and difficulty in adhering. Resveratrol, although with little side effects, has not become a clinical drug. The latest animal experiment is to use the idea of ​​suppressing TGF-β receptor activity from the stem cell perspective to increase muscle and neural stem cells and achieve the goal of restoring youth. However, the decline in stem cell activity is on the one hand the natural manifestation of aging, on the other hand, perhaps the inevitable maintenance of the homeostasis of the environment, rashly regulating this multifunctional important receptor, the many unknown effects that need to be taken care of, and let the stem cells start The effect is similar to the effect of initiating cancer.
 
Scientists at the University of California, Berkeley, have recently discovered that a small molecule drug can rejuvenate aging cells in the brain and muscles of mice. This drug may rejuvenate the body tissues of human aging. The study was published in the journal Oncotarget.
 
Transforming growth factor-β (TGF-β) is a multifunctional protein that affects the growth, differentiation, apoptosis and immune regulation of a variety of cells. TGF-β belongs to the transforming growth factor-β superfamily protein, including three subtypes of β1, β2 and β3. TGF-β can bind to activating cell surface TGF-β receptors. The transforming growth factor-beta receptor is a serine/threonine kinase receptor. Its signal transmission can be through the SMAD signal path [2] and / or DAXX signal path.
 
As we age, some of the biochemicals in the tissue microenvironment will gradually become unbalanced, leading to a gradual decline in stem cell function. The researchers found that aging increases the expression of transforming growth factor (TGF-β) in the hippocampus of the brain, and the downstream signal molecule pSmad3 of TGF-β is also increased. The same changes are also observed in skeletal muscle. TGF-β is produced by microglia and endothelial cells. A small molecule compound of a TGF-β receptor I kinase inhibitor can successfully act on the brain and muscle cells of aged mice, renew the function of stem cells, and make the brain become smarter and stronger. Β2 microglobulin is detected in both mouse brain and muscle, and β2 microglobulin is one of the components of MHC class I molecules. It suggests that TGF-β can promote the occurrence of inflammation in old tissues and does not exercise its traditional immune suppression function. Therefore, inhibition of the TGF-β signaling pathway and normalization of β2 microglobulin can restore the mice to a young state.
 
This study enhances our understanding of old tissue stem cells and uses small molecule compounds that inhibit the TGF-β signaling pathway to alleviate the aging process in the hippocampus of muscles and brain. These findings provide a theoretical basis for the development of new clinical therapeutic drugs that promote the regeneration of muscle and nerves in older animals.