Autophagy: Multiple Mechanisms to Protect Skin from Ultraviolet Radiation-Driven Photoaging

Table 1

Activation of UVR-responsive genes and their association with autophagy.

Gene	Relation to aging	Type of UV radiation	Relation to autophagy	References
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]