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. 2023 Nov 11;63:207–218. doi: 10.1016/j.jare.2023.11.006

Table 1.

BRD4 implicated in aging.

Mechanisms Functions Molecular target Ref
Cell cycle BRD4 inhibition blocks G0/G1 phase Inhibits G1 gene expression (Ccnd1, Ccnd2, Mcm2, Ranbp1, Nid1, Orc2, Pop1, et al.) [29], [30], [31]
G2/M phase Unknown [26]
BRD4 ectopic expression inhibits G0/G1 phase Inhibits RFC-dependent DNA elongation [32]
Apoptosis BRD4 inhibition triggers apoptosis Downregulates c-Myc [45]
Inhibits BRD4-NUT oncogene [46], [47]
Accumulates RNA-DNA hybrids [48]
BRD4 inhibition alleviates apoptosis Inhibits FOXO4-dependent ROS generation through PI3K/AKT pathway [49]
Induces autophagy through MAPK/mTOR/ULK1 pathway [51]
Cell senescence BRD4 inhibition induces cell senescence Blocks telomere elongation [55]
Upregulates p21 expression [57], [58], [59]
BRD4 inhibition alleviates cell senescence Downregulates SASP-related genes [67], [68], [64], [65]
Induces autophagy via AMPK/mTOR/ULK1 pathway [51]
SASP BRD4 inhibition alleviates SASP Inhibits SASP via SE remodeling [64]
Senolysis ARV-825 and JQ1 provoke senolysis Attenuates NHEJ and upregulates autophagic gene expression [70]
Autophagy BRD4 inhibition inhibits autophagy Unknown [92]
BRD4 inhibition promotes autophagy Promotes autophagy and lysosomal biosynthesis through methyltransferase G9a [82]
BRD4 inhibition promotes mitophagy Activates PINK1/Parkin pathway [89]
Mitochondria dysfunction BRD4 inhibition promotes mitochondria dysfunction Increases the levels and activity of OXPHOS protein complexes [94]
BRD4 inhibits mitochondria biogenesis Downregulates PGC-1α gene expression [97]
BRD4 inhibition blocks mitochondria fission Inhibits MFF expression [100]
BRD4 inhibition increases mitochondria fission Inhibits c‐Myc and alters mitochondrial dynamics [39]

RFC: replication factor C; ROS: reactive oxygen species; SASP: senescence-associated secretory phenotype; NHEJ: non-homologous end joining; OXPHOS: oxidative phosphorylation; MFF: mitochondrial fission factor.