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in Keap1 -null MuSCs from female mice, the loss of Keap1 together with estrogen-mediated GSK3 inactivation renders Nrf2 at its highest level, which induces the expression of multiple metabolic genes resulting in metabolic reprogramming, spontaneous activation and gradual depletion of MuSCs

Doubling doses increases side effect risk substantially

Another unifying feature of resistance is signaling pathway redundancy and compensatory network activation

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