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Hepatocyte-specific mitochondrial ribosomal protein CR6-interacting factor 1 (CRIF1) deficiency increases PD-1 expression and creates an adverse environment for T cells, which results in T cell fatigue due to elevated reactive oxygen species and lactate generation [137]

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Although strategies targeting SIRT1 activation (for example, NAD+ boosters) or modulation of p53 acetylation (for example, HDAC inhibitors) have demonstrated potential in protecting ovarian function, a comprehensive evaluation of their specificity and potential off-target effects remains essential (117)