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Alpha-ketoglutarate ameliorates age-related osteoporosis via regulating histone methylations
Alpha-ketoglutarate ameliorates age-related osteoporosis via regulating histone methylations
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Alpha-ketoglutarate ameliorates age-related osteoporosis via regulating histone methylations
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Alpha-ketoglutarate ameliorates age-related osteoporosis via regulating histone methylations
Alpha-ketoglutarate ameliorates age-related osteoporosis via regulating histone methylations
Journal Article

Alpha-ketoglutarate ameliorates age-related osteoporosis via regulating histone methylations

2020
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Overview
Age-related osteoporosis is characterized by the deterioration in bone volume and strength, partly due to the dysfunction of bone marrow mesenchymal stromal/stem cells (MSCs) during aging. Alpha-ketoglutarate (αKG) is an essential intermediate in the tricarboxylic acid (TCA) cycle. Studies have revealed that αKG extends the lifespan of worms and maintains the pluripotency of embryonic stem cells (ESCs). Here, we show that the administration of αKG increases the bone mass of aged mice, attenuates age-related bone loss, and accelerates bone regeneration of aged rodents. αKG ameliorates the senescence-associated (SA) phenotypes of bone marrow MSCs derived from aged mice, as well as promoting their proliferation, colony formation, migration, and osteogenic potential. Mechanistically, αKG decreases the accumulations of H3K9me3 and H3K27me3, and subsequently upregulates BMP signaling and Nanog expression. Collectively, our findings illuminate the role of αKG in rejuvenating MSCs and ameliorating age-related osteoporosis, with a promising therapeutic potential in age-related diseases. α-ketoglutarate is an intermediate of the Krebs Cycle that was recently reported to extend lifespan in C.Elegans. Here, the authors show that administration of α-ketoglutarate to mice reduces age-related bone loss, by ameliorating senescence of bone-marrow derived mesenchymal stem cells.