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。 CLOCK slows down human stem cell aging by stabilizing isochromatin and promotes cartilage regeneration in older animals
In a July 31 paper published online in Cell Research, the core rhythmic protein CLOCK has an antagonists' stem cell aging. Gene therapy based on BLOCK over-expression can alleviate bone and joint degeneration in aging mice and promote joint cartilage regeneration, which provides new ideas and potential intervention targets for delaying human aging and preventing aging-related degenerative diseases.the regulatory mechanism of
biological clock is highly conservative in different species, which makes the physiology and behavior of mammals show rhythmic changes consistent with the 24-hour circadian cycle of the outside world, thus maintaining the dynamic balance of the physiological activity of the body's tissues and cells. Studies have shown that aging and depletion of adult stem cells is one of the important signs of individual aging and a key driving force for degenerative diseases such as degenerative joint lesions in humans.
, however, the regulatory role of the core rhythm protein in the aging process of human adult stem cells is not clear, whether it can delay aging by targeting the core rhythm protein is still to be explored.
researchers found that CLOCK showed downward expression in a variety of human-filled stem cell models with replicated aging, physiological aging, and early childhood aging. Using CRISPR/Cas9-mediated gene editing and stem cell-directed differentiation techniques, they found that the absence of THECH PROTEIN led to accelerated aging of human-charged stem cells.
"CLOCK can form complexes with nuclear fiber layer and isochrome protein, jointly maintain the stability of isochrome structure in the region of the genome repeating element, inhibit the transcript expression of the repetitive element, and thus maintain the stability of the osteogenome and resist the aging of human-charged stem cells. Liang Chuxuan, co-first author of the paper and a doctoral student at the Institute of Zoology of the Chinese Academy of Sciences, told china Science Daily.
addition, over-expression of wild-type BLOCK or transcriptional activation function of the missing mutants, can delay cell aging, suggesting that its mechanism of action does not depend on classical transcription activity.
Qu Jing, co-author of this paper and a researcher at the Institute of Zoology of the Chinese Academy of Sciences, said that injection of THEC zovirus expression vector through joint cavity can reduce the proportion of senescing cells, inhibit inflammatory reactions and stimulate cartilage regeneration, relieve age-related bone and joint degeneration, and improve the motor ability of elderly mice.
" study reveals new functions and mechanisms of core rhythm proteins to regulate human stem cell aging. It expands people's understanding of the new biological function of core rhythm protein, deepens people's understanding of the presumptogenetic mechanism of aging, and opens up ideas for the research of translational medicine of aging. Qu Jing said. (Source: Liu Runan, China Science News Agency)
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