DNA Complexes Research Articles

Probe type optical fiber DNA hybridization biosensor based on polyethylenimine and Poly-L-Lysine surface functionalization method

Nucleotide hybridization technology is an effective method for achieving optical-based selective recognition of nucleotides. Unfortunately, the optimal work performance is always restricted by the lack of the coupling method used to bind sensors with nucleotide sequences. In this work, a series of nucleotide hybridization detection experiments based on optical fiber surface plasmon resonance (SPR) are conducted, aimed at comparing the ability to bind nucleotide of Polyethylenimine (PEI) and Poly-L-Lysine (PLL), which are common coupling agents in optical-based nucleotide hybridization study. In our work, qualitative nucleotide measurements using PEI and PLL are carried out in positive order, negative order, and temperature fluctuation, and confirm PEI has a higher work performance in nucleotide-binding and nucleotide-detection. Quantitative determination in the concentration range of 0–100 nmol/L demonstrates the DNA sensitivity reaches 0.13 nm/(nmol/L) and the detection limit (DL) lies in 4.9 nmol/L, which is outstanding compared with similar optical sensors. In this paper, two kinds of nucleotide molecule detection methods based on optical fiber SPR sensing technology with PEI and PLL are proposed and experimentally verified, and the nucleotide-binding capability of PLL and PEI is contrast analyzed according to experimental results for the first time. This study is of great significance for improving the measurement scheme of DNA sensors and the selection of gene carriers for manufacturing DNA complexes.

Deciphering the binding mechanism of an anti-cancer phytochemical plumbagin with calf thymus DNA using biophysical and in silico techniques.

Plumbagin (PLM), a plant derivative, is well known for a wide range of therapeutic effects in humans including anti-cancer, anti-inflammatory, anti-oxidant, and anti-microbial. Cytotoxic and genotoxic potential of this phytochemical has been studied which demands further insight. DNA being a major target for several drugs was taken to study against PLM to understand its effects on the cellular system. UV-Vis spectroscopy has indicated the binding of PLM to ctDNA and dye displacement assays have confirmed the formation of PLM-ctDNA complex. The insignificant changes in circular dichroism spectra suggested that PLM is not affecting the structural makeup of the ctDNA, hence the binding could be peripheral and not intercalating. Further, the relative viscosity and minimal change in melting temperature upon the complex formation supported this finding and confirmed the groove binding of PLM. Molecular docking analysis and simulation studies also show PLM as a minor groove binder to DNA and provide details on the interaction dynamics of PLM-DNA complex. Docking followed by a 100ns simulation reveals the negative Gibbs free energy change (∆G = -6.6kcalmol-1), and the formation of a stable complex. The PLM- DNA complex with stable dynamics was further supported by different parameters including RMSD, RMSF, SASA, Rg, and the energy profile of interaction. This study provides an insight into the cytotoxic and genotoxic mechanism of PLM which can be a crucial step forward to exploit its therapeutic potential against several diseases including cancer.

SOSSB1 and SOSSB2 mutually regulate protein stability through competitive binding of SOSSA

Human single-stranded DNA-binding protein homologs hSSB1 (SOSSB1) and hSSB2 (SOSSB2) make a vital impact on maintaining genome stability as the B subunits of the sensor of single-stranded DNA complex (SOSS). However, whether and how SOSSB1 and SOSSB2 modulate mutual expression is unclear. This study, demonstrated that the depletion of SOSSB1 in cells enhances the stability of the SOSSB2 protein, and conversely, SOSSB2 depletion enhances the stability of the SOSSB1 protein. The levels of SOSSB1 and SOSSB2 proteins are mutually regulated through their competitive binding with SOSSA which associates with the highly conservative OB-fold domain in SOSSB1 and SOSSB2. The destabilized SOSSB1 and SOSSB2 proteins can be degraded via the proteasome pathway. Additionally, the simultaneous loss of SOSSB1 and SOSSB2 aggravates homologous recombination (HR)-mediated DNA repair defects, enhances cellular radiosensitivity and promotes cell apoptosis. In conclusion, in this study, we showed that SOSSB1 and SOSSB2 positively regulate HR repair and the interaction between SOSSA and SOSSB1 or SOSSB2 prevents the degradation of SOSSB1 and SOSSB2 proteins via the proteasome pathway.

Structural analysis of polysaccharide/antisense DNA complexes during cytoplasmic target mRNA hybridization

We previously demonstrated antisense oligonucleotides (AS-ODNs) delivery system based on the complex formed with poly (dA) and schizophyllan, a type of β-1,3-glucan. This complex enables efficient intracellular delivery of AS-ODNs. In this communication, we investigated the cytoplasmic translocation of the complex itself and its mechanism of action on mRNA. As a result, we found that the complex moved into the cytoplasm while keeping its structure, and AS-ODN hybridized with the target mRNA. This result encourages pharmaceutical applications of the complex.

Laser induced graphene electrochemical aptasensor based on tetrahedral DNA for ultrasensitive on-site detection of microcystin-LR

The development of accurate and reliable sensor for on-site detection of microcystin-LR (MC-LR), one of hazardous environmental pollutants, is highly required. Herein, a laser induced graphene (LIG)-based electrochemical aptasensor for sensitive on-site detection of MC-LR was reported. LIG electrode, the substrate of aptasensor, was prepared via thermal transfer with ethylene-vinyl acetate copolymer, and LIG acted as quasi-reference electrode to replace conventional Ag/AgCl electrode for better operability and robustness. LIG electrode provided large surface area to assemble tetrahedral DNA to absorb methylene blue (MB) for the signal amplification. For detection, the specific recognition of MC-LR with aptamer led to the stripping of tetrahedral DNA complex and further the decreased redox current of MB (IMB). Consequently, the fabricated aptasensor offered high analytical performance for MC-LR detection with a linear range of 1 × 10-2-1 × 105 pM and a detection limit of 3 × 10-3 pM, which was successfully used for water sample analysis with comparable reliability and accuracy of standard method. Furthermore, a portable detection platform by coupling of LIG-based electrochemical aptasensor with electrochemical workstation was constructed for on-site detection of MC-LR. This work offers a novel method for the on-site monitoring of MC-LR, which promotes the investigation of LIG-based electrochemical biosensing in the field of environmental analysis.

DNA and histones impair the mechanical stability and lytic susceptibility of fibrin formed by staphylocoagulase.

Staphylocoagulase (SCG) is a virulence factor of Staphylococcus aureus, one of the most lethal pathogens of our times. The complex of SCG with prothrombin (SCG/ProT) can clot fibrinogen, and SCG/ProT-induced fibrin and plasma clots have been described to show decreased mechanical and lytic resistance, which may contribute to septic emboli from infected cardiac vegetations. At infection sites, neutrophils can release DNA and histones, as parts of neutrophil extracellular traps (NETs), which in turn favor thrombosis, inhibit fibrinolysis and strengthen clot structure. To characterize the combined effects of major NET-components (DNA, histone H1 and H3) on SCG/ProT-induced clot structure, mechanical and lytic stability. Recombinant SCG was used to clot purified fibrinogen and plasma. The kinetics of formation and lysis of fibrin and plasma clots containing H1 or core histones+/-DNA were followed by turbidimetry. Fibrin structure and mechanical stability were characterized with scanning electron microscopy, pressure-driven permeation, and oscillation rheometry. Histones and DNA favored the formation of thicker fibrin fibers and a more heterogeneous clot structure including high porosity with H1 histone, whereas low porosity with core histones and DNA. As opposed to previous observations with thrombin-induced clots, SCG/ProT-induced fibrin was not mechanically stabilized by histones. Similarly to thrombin-induced clots, the DNA-histone complexes prolonged fibrinolysis with tissue-type plasminogen activator (up to 2-fold). The anti-fibrinolytic effect of the DNA and DNA-H3 complex was observed in plasma clots too. Heparin (low molecular weight) accelerated the lysis of SCG/ProT-clots from plasma, even if DNA and histones were also present. In the interplay of NETs and fibrin formed by SCG, DNA and histones promote structural heterogeneity in the clots, and fail to stabilize them against mechanical stress. The DNA-histone complexes render the SCG-fibrin more resistant to lysis and thereby less prone to embolization.

Adineta vaga under fire: simulating the impact of radiation

AbstractPrevious studies have demonstrated the remarkable resistance of bdelloid rotifers to ionizing radiation, making them an interesting model system for studying radiation effects on living organisms. In this study, we use simulations, instead of direct experimental exposures, to examine whether all bdelloids are affected equally by radiation exposure and to explore the relationship between biological data and energy deposition patterns induced by low and high linear energy transfer (LET) radiation. To this end, tool for particle simulation (TOPAS) a simulation tool, widely used in the field of medical physics and radiation therapy, was utilized. Using simulations for proton, iron ions, and X-ray exposure, our findings showed that all individuals, cells, and nuclei were effectively hit by the administered doses of 4 MeV protons, 0.5 GeV/n 56Fe, and X-ray radiation. The results support that the impact on survival and fertility rate measured in Adineta vaga is caused by radiation-induced damage rather than the absence of hits in certain individuals or germinal cells. Notably, simulations revealed significant differences between low- and high-LET radiation concerning irradiated individuals' nuclei. Specifically, for an equivalent dose, high-LET radiation requires fewer incident particles compared to low-LET radiation, resulting in a sparser distribution of radiation hits on the nucleus surface. In conclusion, the study supports the idea that reduced fertility described in high-LET exposed samples is associated with complex DNA damage caused by the condensed energy deposition pattern of high-LET radiation compared to low-LET.

Engineered DNA molecular machine for ultrasensitive detection of environmental lead pollution

Dynamic monitoring of environmental Pb2+ is of utmost importance for food safety and personal well-being. Herein, we report a novel, rapid, and practical fluorescence detection platform for Pb2+. The platform comprises two essential components: an engineered DNAzyme probe (EDP) and a responsive functionalized probe (RFP). The EDP demonstrates specific recognition of Pb2+ and the subsequent release of free DNA fragments. The released DNA fragments are then captured using the RFP to form DNA complexes, which undergo multiple cascade amplification reactions involving polymerases and nickases, resulting in the generation of a large number of fluorescence signals. These signals can detect Pb2+ at concentrations as low as 0.114 nmol/L, with a dynamic range spanning from 0.1 nmol/L to 50 nmol/L. Moreover, the platform exhibits excellent sensitivity and selectivity for Pb2+ detection. To further validate its effectiveness, we successfully quantitatively detected lead contamination in water from Chaohu Lake, and the results aligned closely with those obtained using inductively coupled plasma-mass spectrometry (ICP-MS). Moreover, this platform is suitable for detecting Pb2+ in seawater, soil, and fish samples. These findings confirm the suitability of the current detection platform for the dynamic assessment of Pb contamination in ecological environments, thereby contributing to environmental and food safety.

Exploring Parametric and Mechanistic Differences between Expi293FTM and ExpiCHO-STM Cells for Transient Antibody Production Optimization.

Rapidly producing drug-like antibody therapeutics for lead molecule discovery and candidate optimization is typically accomplished by large-scale transient gene expression technologies (TGE) with cultivated mammalian cells. The TGE methodologies have been extensively developed over the past three decades, yet produce significantly lower yields than the stable cell line approach, facing the technical challenge of achieving universal high expression titers for a broad range of antibodies and therapeutics modalities. In this study, we explored various parameters for antibody production in the TGE cell host Expi293FTM and ExpiCHO-STM with the transfection reagents ExpiFectamineTM and polyethylenimine. We discovered that there are significant differences between Expi293FTM and ExpiCHO-STM cells with regards to DNA complex formation time and ratio, complex formation buffers, DNA complex uptake trafficking routes, responses to dimethyl sulfoxide and cell cycle inhibitors, as well as light-chain isotype expression preferences. This investigation mechanistically dissected the TGE processes and provided a new direction for future transient antibody production optimization.

Mechanistic insights from high resolution DNA damage analysis to understand mixed radiation exposure

Cells exposed to densely ionising high and scattered low linear energy transfer (LET) radiation (50 % dose of each) react more strongly than to the same dose of each separately. The relationship between DNA double strand break location inside the nucleus and chromatin structure was evaluated, using high-resolution transmission electron microscopy (TEM) in breast cancer MDA-MB-231 cells at 30 min post 5 Gy. Additionally, response to high and/or low LET radiation was assessed using single (1 ×1.5 Gy) versus fractionated dose delivery (5 ×0.3 Gy). By TEM analysis, the highest total number of γH2AX nanobeads were found in cells irradiated with alpha radiation just prior to gamma radiation (called mixed beam), followed by alpha, then gamma radiation. γH2AX foci induced by mixed beam radiation tended to be surrounded by open chromatin (lighter TEM regions), yet foci containing the highest number of beads, i.e. larger foci representing complex damage, remained in the heterochromatic areas. The γH2AX large focus area was also greater in mixed beam-treated cells when analysed by immunofluorescence. Fractionated mixed beams given daily induced the strongest reduction in cell viability and colony formation in MDA-MB-231 and osteosarcoma U2OS cells compared to the other radiation qualities, as well as versus acute exposure. This may partially be explained by recurring low LET oxidative DNA damage by every fraction together with a delay in recompaction of chromatin after high LET, demonstrated by low levels of heterochromatin marker H3K9me3 at 2 h after the last mixed beam fraction in MDA-MB-231. In conclusion, early differences in response to complex DNA damage may lead to a stronger cell kill induced by fractionated exposure, which suggest a therapeutic potential of combined high and low LET irradiation.

Implementation of a deep convolution neural network model for identifying and classifying Pleuropulmonary Blastoma on DNA sequences

Pleuro Pulmonary Blastoma is a lung cancer affecting children's lung tissues. The development of the DICER1 gene in the patients leads to PPB. This disease causes trouble breathing along with lung infections. It can only be found by analyzing the DNA sequence of the PPB tissues. The DNA sequence of the tissues affected by cancer is extracted from the infections. The DNA sequences reveal the hereditary cause of the PPB, which can help in detecting the abnormalities of their family members. DNA sequences are complex, and it is impossible to rely on manual clinical methods to give faster and more accurate predictions. Several research works have suggested machine learning models which process the DNA sequences to detect PPB. However, machine learning algorithms cannot understand the complex DNA patterns of cancer tissues. This paper designs and implements a deep learning algorithm, a novel Deep Convolution Neural Network, to overcome such difficulties. The whole DNA sequence can be processed by more layers involved in the DCNN. The proposed DCNN learns the DNA sequence data part by part and compares it with the ground truth values, identifying odd data and abnormal sequence patterns to predict the presence of PPB. The DCNN is implemented in Python software with the DICER1 gene dataset for predicting the PPB. From the result of the experiment, the efficacy of the proposed DCNN model is verified and compared with other traditional models to evaluate the performance. The proposed CNN obtained 98.67% of accuracy for CT image classification and 96% of accuracy for DICER1-DNA data analysis.

Electrospun composite nanofibers of deoxyribonucleic acid and polylactic acid for skincare applications.

The development of useful biomaterials has resulted in significant advances in various fields of science and technology. The demand for new biomaterial designs and manufacturing techniques continues to grow, with the goal of building a sustainable society. In this study, two types of DNA-cationic surfactant complexes were synthesized using commercially available deoxyribonucleic acid from herring sperm DNA (hsDNA, <50 bp) and deoxyribonucleic acid from salmon testes DNA (stDNA, ~2000 bp). The DNA-surfactant complexes were blended with a polylactic acid (PLA) biopolymer and electrospun to obtain nanofibers, and then copper nanoparticles were synthesized on nanofibrous webs. Scanning electron microscopic images showed that all nanofibers possessed uniform morphology. Interestingly, different diameters were observed depending on the base pairs in the DNA complex. Transmission electron microscopy showed uniform growth of copper nanoparticles on the nanofibers. Fourier-transform infrared spectroscopy spectra confirmed the uniform blending of both types of DNA complexes in PLA. Both stDNA- and hsDNA-derived nanofibers showed greater biocompatibility than native PLA nanofibers. Furthermore, they exerted significant antibacterial activity in the presence of copper nanoparticles. This study demonstrates that DNA is a potentially useful material to generate electrospun nanofibrous webs for use in biomedical sciences and technologies.

Studying the interaction between the new neodymium (Nd) complex with the ligand of 1,10-phenanthroline with FS-DNA and BSA.

To learn more about the chemotherapeutic and pharmacokinetic properties of a neodymium complex containing 1,10-phenanthroline (dafone), In vitro binding was investigated with bovine serum albumin and fish-salmon DNA, using a variety of molecular modeling research and biophysical approaches. A variety of spectroscopic techniques including fluorescence and absorption were used to investigate the interplay between DNA/BSA and the neodymium complex. The findings revealed that the Nd complex had a high affinity for BSA and DNA interplays through van der Waals powers. In addition, the binding of the Nd complex to FS-DNA mainly in the groove binding mode clearly reflects with iodide quenching studies, ethidium bromide (EtBr) exclusion assay, ionic strength effect, and viscosity studies. It was observed that the Nd complex binds to FS-DNA through a minor groove with 3.81 × 105(M-1). Also, Kb for BSA at 298K was 5.19×105(M-1), indicating a relatively high affinity of the Nd complex for DNA and BSA. In addition, a competitive study of a docking investigation revealed that the neodymium complex interacts at BSA site III. The results obtained from the binding calculations are well consistent with the experimental findings. Also, cytotoxicity studies of Nd complex were performed in MCF-7 and A-549 cell lines and the results show that this new complex has a selective inhibitory effect on the growth of various cancer cells.

Peroxidase-Mimicking Activity of Nanoceria for Label-Free Colorimetric Assay for Exonuclease III Activity.

We present a novel label-free colorimetric method for detecting exonuclease III (Exo III) activity using the peroxidase-mimicking activity of cerium oxide nanoparticles (nanoceria). Exo III, an enzyme that specifically catalyzes the stepwise removal of mononucleotides from the 3'-OH termini of double-stranded DNA, plays a significant role in various cellular and physiological processes, including DNA proofreading and repair. Malfunctions of Exo III have been associated with increased cancer risks. To assay the activity of Exo III, we applied the previous reports in that the peroxidase-mimicking activity of nanoceria is inhibited due to the aggregation induced by the electrostatic attraction between DNA and nanoceria. In the presence of Exo III, the substrate DNA (subDNA), which inhibits nanoceria's activity, is degraded, thereby restoring the peroxidase-mimicking activity of nanoceria. Consequently, the 3,3',5,5'-tetramethylbenzidine (TMB) substrate is oxidized, leading to a color change from colorless to blue, along with an increase in the absorbance intensity. This approach enabled us to reliably detect Exo III at a limit of detection (LOD) of 0.263 units/mL across a broad dynamic range from 3.1 to 400 units/mL, respectively, with an outstanding specificity. Since this approach does not require radiolabels, complex DNA design, or sophisticated experimental techniques, it provides a simpler and more feasible alternative to standard methods.

Comprehensive Biological, Photodegradation, Density Functional Theory, and Docking Exploration of Zn(II) and Mn(II) complexes of Piroxicam

AbstractThe biological evaluation of coordination complexes is an active research area ascribed to structural modification and synergistic action due to metal ions. The mononuclear complexes of Zn(II) and Mn(II) piroxicam were evaluated for their encyclopedic biological activities, DFT, and docking exploration. Different antioxidant methods were used to assess their antioxidant potential. DNA cleavage and protein binding properties of the complexes were monitored through gel electrophoresis and UV‐visible spectrophotometry. The low IC50 value of both complexes implies more potency than the piroxicam. The percent cleavage and binding constant values indicated that the complexes bind with DNA and BSA more efficiently than the piroxicam. In SD rats, complexes were screened for analgesic, anti‐anxiety, anti‐inflammatory, and anti‐hyperglycemic effects. The complexes demonstrated statistically significant results for in‐vivo analysis. Photodegradation results of the metal complexes under UV lamp exhibited abrupt degradation than the piroxicam. Docking results also validate a better propensity of both complexes to bind with DNA and BSA. Hydrogen bonding and Van der Waals forces play a key role in stabilizing complexes in DNA and BSA binding pockets. These metal complexes have evident therapeutic potential more than piroxicam and could be promising drugs for relieving pain, anxiety, inflammation, and associated comorbidities with good pharmacodynamic properties.

A Novel Neutrophil Extracellular Traps Signature for Overall Survival Prediction and Tumor Microenvironment Identification in Gastric Cancer.

Neutrophil extracellular traps (NETs) released by neutrophils are crucial for cancer development, metastasis, and can indicate gastric cancer (GC) patients' prognosis. This study reveals the relevance of NETs-related genes to GC through transcriptome analysis. We obtained transcriptome sequencing data of GC from UCSC Xena and screened prognostic NETs-related genes by GEPIA2 database. The signature for NETs was subsequently created using the LASSO-Cox regression. The clinical value of model was further explored using the nomogram and was externally validated by the GEO database. After that, we employed GO, KEGG, and GSEA enrichment analyses to evaluate the bio-functional enrichment and related pathways. Additionally, ESTIMATE, MCP counter, and ssGSEA scores were used to investigate the immunological microenvironment of GC patients. Finally, in the external cohort, neutrophil elastase (NE)-DNA complexes were measured by ELISA, and the prognostic value of NE-DNA in GC was investigated using Cox analysis. Seven NETs-associated genes (PDE4B, CD93, CTSG, IL6, ELANE, KCNJ15, and CRISPLD2) were filtered to establish the signature and participated in building the nomogram. In comparison to the high-risk group, the overall survival (OS) was much longer in the low-risk group (P=0.005). The validation cohort demonstrated the acceptable predictive ability of the nomogram. The signature was enriched in biological features such as extracellular matrix organization, epithelial-mesenchymal transition and inflammatory response. Moreover, there were substantial differences in immune cell infiltration across the different risk groups (p<0.001), especially the high-risk group having more immune cells that are engaged in the antigen presentation process and associated functions. Finally, in the external cohort, NE-DNA levels were shown to be an independent factor affecting OS prognosis (p=0.006). Overall, this research identified a novel signature based on seven NETs-associated genes to predict prognosis and identify tumor microenvironment of GC. And high NE-DNA level may be a critical factor in the poor OS associated with NETs.

High specific microRNA detection based on G-quadruplex sensitive fluorescence under isothermal amplification

MicroRNAs (miRNAs) are crucial for various basic cellular processes and have been regarded as an important indicator for pathogenesis and development of cancer. While miRNAs are characterized by short sequence length, large single cell copy number variation, low abundance in vivo, and high homologous sequence similarity. The development of miRNA detection methods with high sensitivity, good selectivity and low cost is the key to study the function of miRNA. In this article, a method combining isothermal chain replacement amplification and G-quadruplex (G4) specific detection is developed for highly specific and sensitive detection of miRNA. By designing proper DNA sequences, a three-stranded DNA complex was formed and produced a lot of G4 structure sequences, which can be stained by specific fluorescence dye and quantified. In the experiment, the fluorescence dye shows extremely high specificity, which brings excellent signal discrimination, so that the target miRNAs can be accurately detected. Experiments under high background noise also verified this method is highly selective for target miRNAs. This method holds great imagination in expanding the detection methods to more platforms, such as nanopore sensors, because it alters the secondary structure of DNA sequences.

Vibrational spectrum and randomness of water at the interface of a protein–DNA complex

Vibrational spectrum and randomness of water at the interface of a protein–DNA complex

Molecular modeling of [VO(L1–4)(R)] complexes (R = bipyridine, phenanthroline): DFT study of antioxidant activity, DNA binding and evaluation of electron-donating and -withdrawing substituent groups

A DFT (density functional theory) study was conducted with eight oxovanadium complexes (C1 – C8) of general formula [VO(L1–4)(R)] (R = bipyridine, phenanthroline; L1–4 = group of ligands derived from dithiocarbamate). The obtained geometries showed a good correlation with the experimental structures. Molecular orbital analysis revealed that the contribution of the L-ligand in the SOMO (single-occupied molecular orbital) of the complexes correlated with the experimental antioxidant activity (IC50), while the contribution of the R-ligand to the LUMO (lowest unoccupied molecular orbital) of the complexes correlated with the experimental complex-DNA interaction (Kb). It has been identified that the presence of an electron-donating substituent group (such as –NH2) in the C5 – C6 structures should enhance these complexes' antioxidant and DNA interaction activities.

The lipidomic correlates of epigenetic aging across the adult lifespan: A population-based study.

Lipid signaling is involved in longevity regulation, but which specific lipid molecular species affect human biological aging remains largely unknown. We investigated the relation between complex lipids and DNA methylation-based metrics of biological aging among 4181 participants (mean age 55.1 years (range 30.0-95.0)) from the Rhineland Study, an ongoing population-based cohort study in Bonn, Germany. The absolute concentration of 14 lipid classes, covering 964 molecular species and 267 fatty acid composites, was measured by Metabolon Complex Lipid Panel. DNA methylation-based metrics of biological aging (AgeAccelPheno and AgeAccelGrim) were calculated based on published algorithms. Epigenome-wide association analyses (EWAS) of biological aging-associated lipids and pathway analysis were performed to gain biological insights into the mechanisms underlying the effects of lipidomics on biological aging. We found that higher levels of molecular species belonging to neutral lipids, phosphatidylethanolamines, phosphatidylinositols, and dihydroceramides were associated with faster biological aging, whereas higher levels of lysophosphatidylcholine, hexosylceramide, and lactosylceramide species were associated with slower biological aging. Ceramide, phosphatidylcholine, and lysophosphatidylethanolamine species with odd-numbered fatty acid tail lengths were associated with slower biological aging, whereas those with even-numbered chain lengths were associated with faster biological aging. EWAS combined with functional pathway analysis revealed several complex lipids associated with biological aging as important regulators of known longevity and aging-related pathways.