Metabolic dysfunction-associated steatotic liver disease (MASLD) is a complex metabolic disorder that encompasses a spectrum of conditions, from simple hepatic steatosis to metabolic-associated steatohepatitis (MASH). MASH is characterized by inflammation and accelerated fibrosis progression, which can ultimately lead to cirrhosis and hepatocellular carcinoma. Given its steadily increasing prevalence, MASLD has emerged as a global health epidemic. Significantly, MASLD represents a stage where liver function can still be partially restored through dietary interventions and physical exercise. However, the long-term sustainability of these lifestyle changes poses a significant challenge. Furthermore, the complex and heterogeneous nature of MASH complicates the development of pharmacotherapeutic strategies and the identification of reliable biomarkers for effective treatment. Therefore, it is essential to gain a comprehensive understanding of the molecular mechanisms driving MASLD and to develop targeted therapeutic interventions. Recent studies have underscored the critical role of post-translational modifications (PTMs) of proteins in regulating MASLD. PTMs, such as ubiquitination, SUMOylation, Neddylation, and UFMylation, are known to modulate protein function and diverse cellular processes. Among these, ubiquitination is particularly noteworthy for its dual role in mediating protein degradation through the ubiquitin-proteasome system and in regulating cellular signaling pathways in a non-proteolytic manner, depending on the specific linkages formed at the seven distinct lysine residues (K6, K11, K27, K29, K33, K48, and K63) and the Met1-linked (M1) linear ubiquitin chain. Despite significant progress in this area, studies focusing on linkage-specific ubiquitination events that regulate MASLD remain relatively limited. Thus, this review aims to provide a comprehensive summary of the role of linkage-specific ubiquitination in regulating MASLD, as well as exploring other ubiquitin-like modifications that may contribute to its pathophysiology.

RNA modifications are key epigenetic alterations that play regulatory functions in RNA biology, including RNA stability and translation. Emerging evidence indicates that RNA modification is crucial for various physiological and pathological processes, including aging. This review describes functions of key RNA modifications, including N⁶-methyladenosine (m⁶A), 5-methylcytosine (m⁵C), N⁷-methylguanosine (m⁷G), 2'-O-methylation (Nm), N¹-methyladenosine (m¹A), adenosine-to-inosine (A-to-I) RNA editing, pseudouridylation (Ψ), and N4-acetylcytidine (ac4C), highlighting their roles in aging and age-associated diseases. We also discuss dynamics of RNA modifications and associated protein factors during aging. This review provides important information on molecular mechanisms underlying aging regulation, focusing on effects of RNA modifications, which can help us understand healthy longevity in humans.

Repeat sequences account for approximately 45% of the human genome, and can produce noncanonical DNA secondary structures that include G-quadruplexes (G4s). Among these, G4s are unique, in that their formation and stability are largely influenced by metal cations, such as Na⁺, K⁺, Ca²⁺, and Mg²⁺. These cations stabilize G4 structures, while also influencing their folding and biological activities. Interactions between G4s and metal ions affect key cellular processes that include transcription, replication, and genome stability. This review highlights the structural diversity and functional roles of G4s, and further explores how their ion-dependent properties have been harnessed for applications in biosensing and therapeutic development. Future research directions to advance G4-targeted technologies for both diagnostic and clinical use are also discussed.

Endothelial cells (ECs) undergo endothelial-to-mesenchymal transition (EndMT) during the pathophysiology of cardiovascular diseases, a complex cellular transdifferentiation process closely associated with increased oxidative stress under adverse conditions such as myocardial infarction (MI). Decursin, a major constituent of Angelica gigas Nakai, displays diverse pharmacological properties. This study aimed to examine the antioxidant impact of decursin on EndMT regulation in both in vitro and in vivo models as a potential therapeutic strategy for MI. In vitro the inhibitory effects of decursin treatment were analyzed by measuring the expression of EndMT-associated genes, assessing endothelial function, intracellular ROS levels, and mitochondrial membrane potential. Furthermore, the study elucidated antioxidation-related signaling mechanisms within EndMT-induced ECs. In vivo, the therapeutic potential of decursin was investigated using a mouse model of MI. Decursin administration attenuated the EndMT process by upregulating CD31 and VE-Cadherin while decreasing fibronectin and α-SMA expression in EndMT-induced ECs. It also lowered ROS levels, preserved mitochondrial membrane potential, and modulated functional properties, resulting in enhanced LDL uptake and diminished endothelial permeability. Endothelial integrity was sustained via regulation of the PI3K/AKT/NF-κB and Smad-dependent signaling pathways, both responsive to oxidative stress during EndMT. In the MI mouse model, decursin reversed EndMT, lessened myocardial fibrosis and apoptosis, and promoted recovery of infarcted regions. The treated hearts demonstrated improved cardiovascular performance. Decursin represents a novel therapeutic strategy targeting intracellular oxidative stress induced by EndMT. By exerting antioxidant activity through the PI3K/AKT/NF-κB and Smad-dependent pathways, decursin maintains endothelial function, suppresses myocardial fibrosis, and supports cardiac recovery following MI therapy.

Lipid metabolism plays an important role in aging and longevity, and lipophagy-a specialized form of autophagy that targets lipid vesicles-regulates lipid homeostasis and alleviates metabolic diseases such as metabolic dysfunctionassociated steatotic liver disease (MASLD). Ilimaquinone (IQ), a sesquiterpene extracted from the sea, is well-known for its various biological effects; however, its effects on lipid metabolism and longevity have not yet been elucidated. In this study, IQ acted in a dose-dependent manner, extending the lifespan of Caenorhabditis elegans (C. elegans) by up to 50%, causing transcriptional changes in 1,878 genes related to fatty acid degradation and longevity pathways. Additionally, IQ reduced lipid accumulation in C. elegans and mouse AML12 cells, as confirmed by Oil Red O staining. RNA sequencing and quantitative reverse transcription polymerase chain reaction validation showed that the expression of key lipid metabolism genes, such as lipl-4 in worms and Lipa in mammalian cells, increased with IQ treatment. Lipophagy has been identified as the key mechanism underlying the lipid-lowering effects of IQ. The inhibition of autophagy by Bafilomycin A1 reversed the reduction in lipid accumulation in both C. elegans and AML12 cells, indicating the involvement of autophagic flux. Western blot analysis demonstrated that IQ activates AMPK, a key regulator of autophagy and lipid metabolism, and inhibits mTOR. IQ increased the turnover of LC3-II and decreased p62 levels, confirming autophagosome formations and increased lysosomal degradation. These findings suggest that IQ promotes autophagy, alleviates lipid accumulation, and has a therapeutic potential for metabolic diseases. In addition, AMPK activation and mTOR inhibition pathways may have contributed to the extension of C. elegans lifespan. Future studies should investigate the potential of IQ in lipid metabolism regulation and lifespan extension.