BACKGROUND: N6-Methyladenosine (m6A) methylation, a common form of RNA modification, play an important role in the pathogenesis of various diseases and in the ontogeny of organisms. Nevertheless, the precise function of m6A methylation in photoaging remains unknown.
OBJECTIVE: This study aims to investigate the biological role and underlying mechanism of m6A methylation in photoaging.
METHODS: m6A dot blot, Real-time quantitative PCR (RT-qPCR), western blot and immunohistochemical (IHC) assays were employed to detect the m6A level and specific m6A methylase in ultraviolet ray (UVR)-induced photoaging tissue. The profile of m6A-tagged mRNA was identified by methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA-seq analysis. Finally, we investigated the regulatory mechanism of KIAA1429 by MeRIP-qPCR, RNA knockdown and immunofluorescence assay.
RESULTS: m6A levels were increased in photoaging and were closely associated with the upregulation of KIAA1429 expression. 1331 differentially m6A methylated genes were identified in the UVR group compared with the control group, of which 1192 (90%) were hypermethylated. Gene ontology analysis showed that genes with m6A hypermethylation and mRNA downregulation were mainly involved in extracellular matrix metabolism and collagen metabolism-related processes. Furthermore, KIAA1429 knockdown abolished the downregulation of TGF-bRII and upregulation of MMP1 in UVR-irradiated human dermal fibroblasts (HDFs). Mechanically, we identified MFAP4 as a target of KIAA1429-mediated m6A modification and KIAA1429 might suppress collagen synthesis through an m6A-MFAP4-mediated process.
CONCLUSIONS: The increased expression of KIAA1429 hinders collagen synthesis during UVR-induced photoaging, suggesting that KIAA1429 represents a potential candidate for targeted therapy to mitigate UVR-driven photoaging.

UNASSIGNED: The mechanism underlying skin photoaging remains elusive because of the intricate cellular and molecular changes that contribute to this phenomenon, which have yet to be elucidated. In photoaging, the roles of keratinocytes and fibroblasts are vital for maintaining skin structure and elasticity. But these cells can get photo-induced damage during photoaging, causing skin morphological changes. Recently, the function of natural active ingredients in treating and preventing photoaging has drawn more attention, with researches often focusing on keratinocytes and fibroblasts.
UNASSIGNED: We searched for studies published from 2007 to January 2024 in the Web of Science, PubMed, and ScienceDirect databases through the following keywords: natural plant, natural plant products or phytochemicals, traditional Chinese Medicine or Chinese herbal, plant extracts, solar skin aging, skin photoaging, and skin wrinkling. This review conducted the accordance of Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines.
UNASSIGNED: In total, 87 researches were included in this review (Figure 1). In keratinocytes, natural compounds may primarily regulate signal pathways such as the NF-κB, MAPK, PI3K/AKT, and Nrf2/ARE pathways, reducing inflammation and cellular damage, thus slowing skin photoaging. Additionally, in fibroblasts, natural active ingredients primarily promote the TGF-β pathway, inhibit MMPs activity, and enhance collagen synthesis while potentially modulating the mTOR pathway, thereby protecting the dermal collagen network and reducing wrinkle formation. Several trials showed that natural compounds that regulate keratinocytes and fibroblasts responses have significant and safe therapeutic effects.
UNASSIGNED: The demand for natural product-based ingredients in sunscreen formulations is rising. Natural compounds show promising anti-photoaging effects by targeting cellular pathways in keratinocytes and fibroblasts, providing potential therapeutic strategies. However, comprehensive clinical studies are needed to verify their efficacy and safety in mitigating photoaging, which should use advanced pharmacological methods to uncover the complex anti-photoaging mechanisms of natural compounds.

The use of plastic bowls (PB) has garnered increasing scrutiny due to the inevitable generation of microplastics (MPs) throughout their lifecycle. Despite this concern, there exists a limited understanding of the behaviors, toxicological effects, and mechanisms associated with aged PB (A-PB). This research investigated the photoaging properties of A-PB following ultraviolet irradiation and evaluated the neurotoxic impact of exposure to A-PB at environmentally relevant concentrations (0.001-1 mg/L) on Caenorhabditis elegans. Significant alterations in the crystallinity, elemental composition, and functional groups of A-PB were observed compared to virgin PB (V-PB), along with the emergence of environmentally persistent free radicals and reactive oxygen species. Toxicity assessments revealed that exposure to 0.1-1 mg/L A-PB induced greater neurotoxicity on locomotion behaviors compared to V-PB, as evidenced by marked reductions in head thrashes, body bends, wavelength, and mean amplitude. Exposure to A-PB also altered the fluorescence intensities and neurodegeneration percentage of dopaminergic, serotonergic, and GABAergic neurons, suggesting neuronal damage in the nematodes. Correspondingly, decreases in the levels of dopamine, serotonin, and GABA were noted together with significant drops in the expression of neurotransmitter-related genes (e.g., dat-1, tph-1, and unc-47). Correlation analyses established a significant positive relationship between these genes and locomotion behaviors. Further exploration showed the absence of locomotion behaviors in dat-1 (ok157), tph-1 (mg280), and unc-47 (e307) mutants, underscoring the pivotal roles of the dat-1, tph-1, and unc-47 genes in mediating neurotoxicity in C. elegans. This study sheds light on the photoaging characteristics and heightened toxicity of A-PB, elucidating the mechanisms driving A-PB-induced neurotoxicity.

Aging is associated with significant changes to skin structure and function. As the United States population ages, dermatologists are increasingly presented with the clinical consequences of these changes. Understanding the biology of aging skin allows dermatologists to best guide patients towards proactive treatment of age-related skin disease. The first article of this 2-part continuing medical education series reviews the structural, molecular and functional changes associated with skin aging.

Excessive UV exposure can lead to skin roughness, wrinkles, pigmentation, and reduced elasticity, with severe cases potentially causing skin cancer. Nowadays, various anti-photoaging strategies have been developed to maintain skin health. Among them, dietary supplements with anti-photoaging properties are gaining increasing attention. Yak whey protein (YWP) possesses multiple benefits, including anti-inflammatory, antioxidant, and immune-boosting properties, effectively protecting the skin. This study used a mixed UVA and UVB light source to irradiate a nude mouse model, exploring the advantages of YWP in anti-photoaging and regulating gut microbiota. The results indicated that YWP alleviated UV-induced skin damage, wrinkles, dryness, and reduced elasticity by inhibiting oxidative stress, inflammatory factors (IL-1α, IL-6, and TNF-α), and matrix metalloproteinases (MMP-1, MMP-3, and MMP-12), thereby increasing the levels of elastin, type I collagen, and type III collagen in the extracellular matrix (ECM). Additionally, YWP significantly improved the abundance of Firmicutes and Bacteroidota in the gut microbiota of mice, promoting the growth of beneficial bacteria such as Lachnospiraceae_NK4A136_group, Ruminococcus_torques_group, and Clostridia_UCG_014, mitigating the dysbiosis caused by photoaging. These findings underscore the potential of YWP in anti-photoaging and gut microbiota improvement, highlighting it as a promising functional food for enhancing skin and gut health.

The epidermal barrier is vital for protecting the skin from environmental stressors and ultraviolet (UV) radiation. Filaggrin-2 (FLG2), a critical protein in the stratum corneum, plays a significant role in maintaining skin barrier homeostasis. However, the precise role of FLG2 in mitigating the adverse effects of UV-induced barrier disruption and photoaging remains poorly understood. In this study, we revealed that UVB exposure resulted in a decreased expression of FLG2 in HaCaT keratinocytes, which correlated with a compromised barrier function. The administration of recombinant filaggrin-2 (rFLG2) enhanced keratinocyte differentiation, bolstered barrier integrity, and offered protection against apoptosis and oxidative stress induced by UVB irradiation. Furthermore, in a UV-induced photodamage murine model, the dermal injection of rFLG2 facilitated the enhanced restoration of the epidermal barrier, decreased oxidative stress and inflammation, and mitigated the collagen degradation that is typical of photoaging. Collectively, our findings suggested that targeting FLG2 could be a strategic approach to prevent and treat skin barrier dysfunction and combat the aging effects associated with photoaging. rFLG2 emerges as a potentially viable therapy for maintaining skin health and preventing skin aging processes amplified by photodamage.

Microplastics (MPs) in coastal wetlands have been of great concern, but information on the aging behavior of MPs in the sediment-water interface is still lacking. In this study, the contribution of a typical abiotic (photoaging) and biotic (biodegradation) process and the underlying aging pathway of MPs with different degradabilities (including polypropylene, polyethylene terephthalate, and polylactic acid) were studied. With a quantified relative importance of photoaging (>55%) vs biodegradation, the crucial contribution of photoaging on MP aging was highlighted. This was likely attributed to more generation of reactive oxygen species (ROS) under sunlight irradiation conditions, containing O2•- and H2O2. By raising higher the level of malondialdehyde (0.5-3.5 times as high as that in the dark condition), these photochemically formed ROS caused oxidative stress and inhibited the selective attachment of plastic-degrading microbes on the MP surface, thereby weakening the effect of biodegradation. On this basis, the aging characteristics and potential pathway of different MPs were revealed. The functional group of nondegradable polypropylene tends to be broken by ROS first, while biodegradation (Arthrobacter oryzae and Bacillus sp.) played a relatively dominant role in biodegradable polylactic acid. This study provides a new sight for the understanding on the aging behaviors of MPs in the sediment-water interface.

Skin aging is a complex biological process affected by a plethora of intrinsic and extrinsic factors that alter cutaneous functions through the modulations of signaling pathways and responses. Expressed in various cell types and skin tissue layers, G protein-coupled receptors (GPCRs) play a vital role in regulating skin aging. We have cataloged 156 GPCRs expressed in the skin and reviewed their roles in skin aging, such as pigmentation, loss of elasticity, wrinkles, rough texture, and aging-associated skin disorders. By exploring the GPCRs found in the skin, it may be possible to develop new treatment regimens for aging-associated skin conditions using GPCR ligands.

Cathelicidins, a category of critical host defense molecules in vertebrates, have been extensively studied for their bactericidal functions, but little is known about their non-bactericidal properties. Herein, a novel cathelicidin peptide (Atonp2) was identified from the plateau frog Nanorana ventripunctata. It did not exhibit bactericidal activity but showed significant therapeutic effects in chronic UVB radiation-induced mouse skin photoaging through inhibiting thickening, pyroptosis and inflammation in the epidermis, while inhibiting cellular senescence, collagen fibre breakage and type Ⅰ collagen reduction in the dermis. Further studies indicated that Atonp2 effectively scavenged UVB-induced intracellular ROS via tyrosines at positions 9 and 10, while activating the Keap1/Nrf2 pathway to protect epidermal keratinocytes against UVB radiation, which in turn indirectly reversed the senescence and collagen degradation of dermal fibroblasts, thereby ameliorating UVB-induced skin photoaging. As such, this study identified a non-bactericidal cathelicidin peptide with potent antioxidant functions, highlighting its potential to treat and prevent skin photoaging.

Ultraviolet (UV) exposure causes damage to human skin and mucous membranes, resulting in oxidative stress, and can also lead to inflammation of human skin, skin aging, and even diseases such as squamous cell carcinoma and melanoma of the skin. The main means of protection against UV radiation is physical shielding and the use of sunscreen products. Carbon dots as a novel nanomaterial provide a new option for UV protection. In this article, we introduced sulfhydryl groups to synthesize l-cysteine-derived carbon dots (GLCDs) with UV resistance. GLCDs exhibit high-efficiency and excellent UV absorption, achieving 200-400 nm UV absorption (99% UVC, 97% UVB, and 86% UVA) at a low concentration of 0.5 mg/mL. Meanwhile, GLCDs can reduce apoptosis and UVB-induced oxidative damage, increase collagen type I gene expression, and inhibit skin aging in zebrafish. It also inhibits senescence caused by the senescence inducer 2,2\'-azobis(2-methylpropionamidine) dihydrochloride and reduces oxidative damage. The above studies show that GLCDs possess efficient broad-spectrum UV absorption, antiphotoaging, and antiaging capabilities, which will have a broad application prospect in UV protection.