Role of autophagy in skin photoaging: A narrative review

Abstract

As the largest organ of the human body, the skin serves as the primary barrier against external damage. The continuous increase in human activities and environmental pollution has resulted in the ongoing depletion of the ozone layer. Excessive exposure to ultraviolet (UV) radiation enhances the impact of external factors on the skin, leading to photoaging. Photoaging causes physical and psychological damage to the human body. The prevention and management of photoaging have attracted increased attention in recent years. Despite significant progress in understanding and mitigating UV-induced photoaging, the precise mechanisms through which autophagy contributes to the prevention of photoaging remain unclear. Given the important role of autophagy in repairing UV-induced DNA damage and scavenging oxidized lipids, autophagy is considered a novel strategy for preventing the occurrence of photoaging and other UV light-induced skin diseases. This review aims to elucidate the biochemical and clinical features of photoaging, the relationship of skin photoaging and chronological aging, the mechanisms underlying skin photoaging and autophagy, and the role of autophagy in skin photoaging.

Figure 1.

Mechanisms underlying skin photoaging (drawn using Figdraw). Arrows indicate activating effects. Ultraviolet (UV) radiation directly and indirectly disturbs the in vivo homeostasis of the skin, induces oxidative and mitochondrial stress, and exacerbates skin photoaging. The panel in the image depicts the aberrant function of multiple signaling pathways and factors that maintain cellular health. AMPK = 5´AMP-activated protein kinase, AKT = AKT serine/threonine protein kinase, AP-1 = activator protein 1, Bcl-2 = B-cell lymphoma-2, ERK = extracellular signal regulated protein kinase, IL-1 = interleukin-1, MMPs = matrix metalloproteinases, MAPK = mitogen-activated protein kinase, NF-κB = nuclear factor kappa light-chain enhancer of activated B cells, PI3K = phosphatidyl inositol 3 kinase, ROS = reactive oxygen species, Ras = Rat sarcoma protein, Raf = mitogen-activated protein kinase, SASP = senescence-associated secretory phenotype, TNF-α=tumor necrosis factor alpha, UVA = ultraviolet A, UVB = ultraviolet B, UVC = ultraviolet C.

Figure 2.

Process of autophagy (drawn using Figdraw). Arrows indicate activating effects and flat heads indicate inhibiting effects. Mitochondrial autophagy occurs through ubiquitin-dependent or ubiquitin-independent pathways.ULK complex (ULK1, ATG13, and FIP200) which is inhibited by mTOR is formed in the presence of cargo encompassing damaged mitochondria. The class III PI3K complex (Atg14, Vps34, and Beclin1) plays a crucial role in autophagosome formation by generating PI3K, which in turn recruits downstream ubiquitin-like conjugation systems (Atg5, Atg12, and Atg16L) and facilitates the conversion of LC3-I to LC3-PE. Then the fusion of lysosomes with autophagosomes forms autolysosomes. Finally, the degraded cargos are digested and the productions are recycled back to cytoplasm by lysosomal hydrolase. Ambra1 = autophagy and Beclin 1 regulator 1, Atg = autophagy-related protein, AMPK = adenosine 5´-monophosphate (AMP)-activated protein kinase, ALFY = autophagy-linked FYVE protein, BNIP3 = Bcl2 interacting protein 3, FIP 200 = FAK family kinase-interacting protein of 200 kDa, LC3 = microtubule-associated light-chain protein 3 1A/1B, mTOR = mammalian target of rapamycin, NBR1 = neighbor of BRCA1 gene 1, PINK1 = PTEN-induced kinase 1,Parkin = E3-ubiquitin (Ub) ligase, PI3K = phosphatidyl inositol 3 kinase, PE = phosphatidylethanolamines, PARL = presenilin associated rhomboid like, SQSTM1/ p62 = adaptor protein sequestosome 1,ULK1 = Unc-51-like autophagy-inhibiting kinase 1.

Figure 3.

Role of autophagy in skin photoaging (drawn using Figdraw). Arrows indicate activating effects. The unique physical attributes of solar radiation facilitate its penetration into the skin and its interaction with cells at different depths, resulting in distinct and interconnected biological responses. ROS = reactive oxygen species, UVA = ultraviolet A, UVB = ultraviolet B.