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Klotho defect leads to the increased cellular senescence and secretion of SASPs ( 4.2.5 Sirtuins deficiency Sirtuins (SIRTs) are a group of NAD + -dependent deacetylases (Morigi et al., 2018), which has a deep impact on a variety of cytokines and signaling pathways related to cellular senescence, such as FOXO, p53 (Li et al., 2019), NF-B, NRF2/ARE pathway (Zhuang et al., 2021), PTEN-induced putative kinase 1 (PINK1)/parkin axis (Liu et al., 2020), signal transducer and activator of transcription 3 (STAT3) (Sun et al., 2021), and hypoxia inducible factor (HIF)-2 (Li et al., 2021)