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Gene | Relation to aging | Type of UV radiation | Relation to autophagy | References |
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mTOR (mTORC1 and mTORC2) | mTORC1 suppresses RAS-induced senescence, and mTORC2 induces skin aging through activation of NF-κB cascade | UVB activates the mTORC2/Akt/IKKα pathway | mTOR negatively regulates autophagy via Atg13, ULK1, and ULK2 | [73–77] |
Sirtuins | Sirtuins modulate lifespan, while SIRT-1 inhibits senescence | UV exposure deceases SIRT-1 in skin keratinocytes | SIRT-1 induces autophagy through deacetylation and activation of autophagy-related genes ATG5, ATG7, and ATG8/LC3. | [40, 78–83] |
FoxOs | FoxOs are regulated by IGF-1, while IGF-1 induces aging | FoxO3 induces autophagy by glutamine metabolism; FoxO1 overexpression induces autophagic flux formation | UVA and UVB radiation decreases FoxO1 expression in fibroblasts | [84–89] |
PPARδ | PPARδ prevents photoaging by the inhibition of MMP-1 | UVB attenuates PPARδ through the induction of MMP-1 secretion | PPARδ activation induces autophagy marker Beclin-1 and LC3 expression | [90, 91] |
Hsp70 | eHsp70 treatment prolongs lifespan of mice | UVB chronic exposure induces ROS-mediated apoptosis and decreases macrophagy | HSPA8/HSC70 plays an important role in chaperone-mediated autophagy. Hsp70 links to the proteasome shuttle factor UBQLN2 to degrade misfolded proteins | [92–96] |
Nrf2 | Nrf2 deficiency in mice following UVB irradiation promotes mouse photoaging; repression of the Nrf2-mediated antioxidative response contributes to premature aging | UVA exposure increases Nrf2 expression in fibroblasts. UVB induces mouse photoaging by Nrf2 depletion | Nrf2 knockout reduces expression of autophagic genes in embryo fibroblasts | [97, 98] |
HO-1 | Disturbances in HO-1 level are associated with age-dependent disorder pathogenesis | Both UVA and UVB induce detoxifying enzyme HO-1 expression | HO-1 and autophagy are upregulated by LPS in primary mouse hepatocytes; pharmacological knockdown or inhibition of HO-1 prevents autophagy | [99–108] |
NF-κB | NF-κB pathway is involved in progression of aging, and NF-κB inhibition attenuates oxidative stress, DNA damage, and delayed cellular senescence | UV activates NF-κB to form two phases Curcumin combined with UVA induces apoptosis by inhibition of NF-κB activity, and UVA exposure activates NF-κB | Inhibition of NF-κB promotes autophagy, while autophagy suppression restores NF-κB activity | [109–125] |
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