Table 2.
Histone ubiquitination and O-GlcNAcylation during Immunosenescence
| Potential Target | Modification Sites | Enzyme | Model | Mechanism | Effect | References |
|---|---|---|---|---|---|---|
| Ubiquitination | K1642 | CHIP | Mouse model of osteoarthritis (OA) | DPP4 competitively binds to the K1642 site of MYH9, blocking CHIP-mediated ubiquitin-proteasomal degradation, and the accumulation of MYH9 triggers excessive mitochondrial fission and exacerbates oxidative stress | Promotes aging | [13] |
| - | Parkin | IVDD rat model | SPP1 inhibits mitophagy by blocking the PINK1/PARKIN pathway, accelerating nucleus pulposus cell degeneration and inducing calcification | Promotes aging | [198] | |
| – | Diabetic nephropathy (DN) mouse model | Parkin ubiquitinates GATA4, downregulating the GATA4/GAS1 signaling pathway and alleviating inflammation and fibrosis in renal tubular epithelial cells (RTEC) | Delays aging | [14] | ||
| – | FBXL19 | Cardiovascular injury model related to influenza A virus (IAV) infection | Enhances the innate immune response, inhibits inflammation and cell aging | Delays aging and protects the heart | [15] | |
| – | MKRN1 | Endothelial cell (ECs) aging and activation model | High expression of MKRN1 induced by d-flow ubiquitinates and degrades related regulatory molecules, activates the NF - κB pathway and the cell aging program, and exacerbates endothelial cell dysfunction and promotes atherosclerosis | Promotes aging | [199] | |
| K142 | HRD1 | Neuron aging model exposed to cadmium chloride (CdCl₂) | Cadmium chloride exposure activates the SEL1L/ hrd1-mediated ERAD system, leading to ubiquitination of SigmaR1 | Promotes aging | [200] | |
| – | HECTD1 | RAW264.7 cell aging model | KL targets HECTD1, inhibits IRS1 ubiquitin-proteasomal degradation, regulates macrophage aging and function, and alleviates diabetic retinopathy | Promotes aging | [201] | |
| K63 | Pellino-1 | D-gal-induced mouse aging model | Pellino - 1 ubiquitinates p21 via the K63 site and participates in the aging process of lung cells and the development of COPD | Promotes aging | [202] | |
| – | MDM2 | 2-year naturally aging mouse model | MDM2 ubiquitination promotes HDAC1 degradation and promotes kidney aging | Promotes aging | [191] | |
| – | UBE2E3 | Aging Sertoli cell (SCs) model | miR - 143 - 3p targets UBE2E3, restricting SCs proliferation and disrupting the blood-testis barrier | Promotes aging | [202] | |
| – | RAD6B | RAD6B knockout (KO) mouse model | RAD6B deficiency disrupts the PEDF signal, activates DNA damage, aging, and apoptosis pathways, and accelerates retinal degeneration | Delays aging | [204] | |
| K13/K15 | USP14 | D - gal-induced POI mouse model | Abnormally high expression of USP14 disrupts the DDR function of granulosa cells | Promotes ovarian aging | [205] | |
| – | USP11 | Unilateral ureteral obstruction (UUO) mouse model | USP11 deubiquitinates Tgfbr2 to reduce its degradation, activating the downstream aging signaling pathway | Promotes kidney aging and fibrosis | [206] | |
| – | USP13 | USP13 knockout mouse model | USP13 participates in the lung aging signaling pathway by regulating the K63-linked ubiquitination and protein stability of MDM2 | Promotes lung aging | [207] | |
| – | USP18 | Human coronary artery endothelial cells (HCAECs) | USP18 participates in the regulation of inflammation via the ubiquitination pathway | Delays aging | [208] | |
| – | USP30 | D - gal-treated cell aging model | USP30 antagonizes Parkin and negatively regulates mitophagy, accelerating cardiomyocyte aging | Promotes aging | [209] | |
| – | USP3 | Primary articular chondrocyte model | USP3 upregulates SIRT3 and inhibits IL - 1β-induced chondrocyte aging | Delays aging | [210] | |
| O-GlcNAcylation | Ser470/Thr493 | OGT | C. elegans model | OGT-1 can catalyze the O-GlcNAc glycosylation modification of the Ser470 and Thr493 sites of the SKN-1 protein, thereby affecting the accumulation, activity of SKN-1 in the intestinal nucleus, and the lifespan and oxidative stress resistance of nematodes | Delays aging | [16] |
| – | OGT | OGT knockout mouse model | Decreased levels of OGT and O - GlcNAcylation in the brains of aging mice lead to cognitive impairment. Regulating OGT promotes cognitive rejuvenation | Delays aging | [214] | |
| – | OGA | O - GlcNAcylation overexpressing C57BL/6J mouse model | Inhibition of OGA affects AD treatment | Delays aging | [17, 215] | |
| – | OGT, OGA | Transient cerebral ischemia stroke model | The XBP1s/HBP/O - GlcNAc axis regulates neuroprotection in ischemic stroke | Delays aging | [216] | |
| Thr699 | OGT, OGA | – | Modifies β - hydroxybutyrylation (Kbhb), enhances the interaction between STAT1 and IFNAR2, and enhances the antiviral response mediated by ifn - i | Delays aging | [217] |