Improved resilience and proteostasis mediate longevity upon DAF-2 degradation in old age.

Little is known about the possibility of reversing age-related biological changes when they have already occurred. To explore this, we have characterized the effects of reducing insulin/IGF-1 signaling (IIS) during old age. Reduction of IIS throughout life slows age-related decline in diverse species, most strikingly in the nematode Caenorhabditis elegans. Here we show that even at advanced ages, auxin-induced degradation of DAF-2 in single tissues, including neurons and the intestine, is still able to markedly increase C. elegans lifespan. We describe how reversibility varies among senescent changes. While senescent pathologies that develop in mid-life were not reversed, there was a rejuvenation of the proteostasis network, manifesting as a restoration of the capacity to eliminate otherwise intractable protein aggregates that accumulate with age. Moreover, resistance to several stressors was restored. These results support several new conclusions. (1) Loss of resilience is not solely a consequence of pathologies that develop in earlier life. (2) Restoration of proteostasis and resilience by inhibiting IIS is a plausible cause of the increase in lifespan. And (3), most interestingly, some aspects of the age-related transition from resilience to frailty can be reversed to a certain extent. This raises the possibility that the effect of IIS and related pathways on resilience and frailty during aging in higher animals might possess some degree of reversibility.

Potassium Iodide Doping for Vacancy Substitution and Dangling Bond Repair in InP Core-Shell Quantum Dots.

This work highlights the novel approach of incorporating potassium iodide (KI) doping during the synthesis of In0.53P0.47 core quantum dots (QDs) to significantly reduce the concentration of vacancies (i.e., In vacancies; VIn-) within the bulk of the core QD and inhibit the formation of InPOx at the core QD-Zn0.6Se0.4 shell interfaces. The photoluminescence quantum yield (PLQY) of ~97% and full width at half maximum (FWHM) of ~40 nm were achieved for In0.53P0.47/Zn0.6Se0.4/Zn0.6Se0.1S0.3/Zn0.5S0.5 core/multi-shell QDs emitting red light, which is essential for a quantum-dot organic light-emitting diode (QD-OLED) without red, green, and blue crosstalk. KI doping eliminated VIn- in the core QD bulk by forming K+-VIn- substitutes and effectively inhibited the formation of InPO4(H2O)2 at the core QD-Zn0.6Se0.4 shell interface through the passivation of phosphorus (P)-dangling bonds by P-I bonds. The elimination of vacancies in the core QD bulk was evidenced by the decreased relative intensity of non-radiative unpaired electrons, measured by electron spin resonance (ESR). Additionally, the inhibition of InPO4(H2O)2 formation at the core QD and shell interface was confirmed by the absence of the {210} X-ray diffraction (XRD) peak intensity for the core/multi-shell QDs. By finely tuning the doping concentration, the optimal level was achieved, ensuring maximum K-VIn- substitution, minimal K+ and I- interstitials, and maximum P-dangling bond passivation. This resulted in the smallest core QD diameter distribution and maximized optical properties. Consequently, the maximum PLQY (~97%) and minimum FWHM (~40 nm) were observed at 3% KI doping. Furthermore, the color gamut of a QD-OLED display using R-, G-, and B-QD functional color filters (i.e., ~131.1%@NTSC and ~98.2@Rec.2020) provided a nearly perfect color representation, where red-light-emitting KI-doped QDs were applied.

Intravascular Imaging and Angiography Guidance in Complex Percutaneous Coronary Intervention Among Patients With Diabetes: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Data are limited regarding the effects of intravascular imaging guidance during complex percutaneous coronary intervention (PCI) in patients with diabetes. Objective: To compare the clinical outcomes of intravascular imaging-guided vs angiography-guided complex PCI in patients with or without diabetes. Design, Setting, and Participants: This prespecified secondary analysis of a subgroup of patients in RENOVATE-COMPLEX-PCI (Randomized Controlled Trial of Intravascular Imaging Guidance Versus Angiography-Guidance on Clinical Outcomes After Complex Percutaneous Coronary Intervention), an investigator-initiated, open-label multicenter trial, analyzed enrolled patients who underwent complex PCI at 20 sites in Korea from May 2018 through May 2021. Eligible patients were randomly assigned in a 2:1 ratio to undergo either the intravascular imaging-guided PCI or angiography-guided PCI. Data analyses were performed from June 2023 to April 2024. Interventions: Percutaneous coronary intervention was performed either under the guidance of intravascular imaging or angiography alone. Main Outcomes and Measures: The primary end point was target vessel failure (TVF), defined as a composite of cardiac death, target vessel-related myocardial infarction, or target vessel revascularization. Results: Among the 1639 patients included in the analysis (mean [SD] age, 65.6 [10.2] years; 1300 males [79.3%]), 617 (37.6%) had diabetes. The incidence of TVF was significantly higher in patients with diabetes than patients without diabetes (hazard ratio [HR], 1.86; 95% CI, 1.33-2.60; P < .001). Among patients without diabetes, the intravascular imaging-guided PCI group had a significantly lower incidence of TVF compared with the angiography-guided PCI group (4.7% vs 12.2%; HR, 0.41 [95% CI, 0.25-0.67]; P < .001). Conversely, in patients with diabetes, the risk of TVF was not significantly different between the 2 groups (12.9% vs 12.3%; HR, 0.97 [95% CI, 0.60-1.57]; P = .90). There was a significant interaction between the use of intravascular imaging and diabetes for the risk of TVF (P for interaction = .02). Among patients with diabetes, only those with good glycemic control (hemoglobin A1c level ≤7.5%) and who achieved stent optimization by intravascular imaging showed a lower risk of future ischemic events (HR, 0.31; 95% CI, 0.12-0.82; P = .02). Conclusions and Relevance: In this secondary analysis of a subgroup of patients in the RENOVATE-COMPLEX-PCI trial, intravascular imaging guidance reduced the risk of TVF compared with angiography guidance in patients without diabetes (but not in patients with diabetes) during complex PCI. In patients with diabetes undergoing complex PCI, attention should be paid to stent optimization using intravascular imaging and glycemic control to improve outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT03381872.

Increased risk of epilepsy after transient global amnesia: A population-based study in South Korea.

PURPOSE: This study aimed to investigate the risk of epilepsy after transient global amnesia (TGA). METHODS: Study population was recruited using the International Classification of Diseases codes from the Korean National Health Insurance Service database between 2002 and 2020. The incidence of epilepsy was compared between the TGA (n=12,390) and non-TGA (n=33,868) groups, determined using 1:3 propensity score matching. Using Cox proportional hazard regression model, we obtained adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for incident epilepsy in the TGA compared with non-TGA group. Logistic regression was performed to examine the independent variables determining incident epilepsy in the TGA group, and adjusted odds ratios (aORs) and 95% CIs were calculated. RESULTS: The TGA group had a significantly higher cumulative incidence of epilepsy than controls (p <0.001, log-rank test). TGA was significantly associated with incident epilepsy in the Cox model (adjusted HR 1.46, 95% CI 1.36-1.56). The adjusted logistic regression showed that age (per 1 year, aOR 1.02, 95% CI 1.01-1.02), female sex (aOR 0.68, 95% CI 0.60-0.77), hypertension (aOR 1.14, 95% CI 1.00-1.30), diabetes (aOR 1.26, 95% CI 1.10-1.44), stroke (aOR 1.22, 95% CI 1.06-1.40), depression (aOR 1.44, 95% CI 1.22-1.69), anxiety (aOR 1.31, 95% CI 1.14-1.51), alcohol-related disease (aOR 1.96, 95% CI 1.38-2.78), low income (aOR 1.18, 95% CI 1.02-1.36) and rural residence (aOR 1.20, 95% CI 1.02-1.42) were associated with incident epilepsy. CONCLUSIONS: Our results suggest a longitudinal association of TGA with incident epilepsy.

Brightening deep-blue perovskite light-emitting diodes: A path to Rec. 2020.

Deep-blue perovskite light-emitting diodes (PeLEDs) of high purity are highly sought after for next-generation displays complying with the Rec. 2020 standard. However, mixed-halide perovskite materials designed for deep-blue emitters are prone to halide vacancies, which readily occur because of the low formation energy of chloride vacancies. This degrades bandgap instability and performance. Here, we propose a chloride vacancy-targeting passivation strategy using sulfonate ligands with different chain lengths. The sulfonate groups have a strong affinity for lead(II) ions, effectively neutralizing vacancies. Our strategy successfully suppressed phase segregation, yielding color-stable deep-blue PeLEDs with an emission peak at 461 nanometers and a maximum luminance (Lmax) of 2707 candela per square meter with external quantum efficiency (EQE) of 3.05%, one of the highest for Rec. 2020 standard-compliant deep-blue PeLEDs. We also observed a notable increase in EQE up to 5.68% at Lmax of 1978 candela per square meter with an emission peak at 461 nanometers by changing the carbon chain length.

Three new nonenes from culture broth of marine-derived fungus Albifimbria verrucaria and their cytotoxic and anti-viral activities.

Three new nonenes, verrucanonenes A‒C (1‒3), were isolated from culture broth of marine-derived fungus Albifimbria verrucaria. These compounds were isolated using silica gel column chromatography, reversed-phase medium pressure liquid chromatography, Sephadex LH-20 column chromatography, and preparative HPLC. Their structures were determined using a spectroscopic method. Cytotoxicities of these isolated compounds to A549, DU145, HCT116, and HT1080 cancer cell lines were assessed. Compounds 1‒3 exhibited cytotoxicities to DU145 cancer cell line, with IC50 values of 23.4, 28.6, and 20.1 µM, respectively. Compound 2 decreased H1N1-induced cytopathic effects on MDCK cells in a dose-dependent manner.

Locating carbon neutral mobility hubs using artificial intelligence techniques.

This research proposes a novel, three-tier AI-based scheme for the allocation of carbon-neutral mobility hubs. Initially, it identified optimal sites using a genetic algorithm, which optimized travel times and achieved a high fitness value of 77,000,000. Second, it involved an Ensemble-based suitability analysis of the pinpointed locations, using factors such as land use mix, densities of population and employment, and proximities of parking, biking, and transit. Each factor is weighted by its carbon emissions contribution, then incorporated into a suitability analysis model, generating scores that guide the final selection of the most suitable mobility hub sites. The final step employs a traffic assignment model to evaluate these sites' environmental and economic impacts. This includes measuring reductions in vehicle kilometers traveled and calculating other cost savings. Focusing on addressing sustainable development goals 11 and 9, this study leverages advanced techniques to enhance transportation planning policies. The Ensemble model demonstrated strong predictive accuracy, achieving an R-squared of 95% in training and 53% in testing. The identified hubs' sites reduced daily vehicle travel by 771,074 km, leading to annual savings of 225.5 million USD. This comprehensive approach integrates carbon-focused analyses and post-assessment evaluations, thereby offering a comprehensive framework for sustainable mobility hub planning.

Impact of Intravascular Imaging-Guided Stent Optimization According to Clinical Presentation in Patients Undergoing Complex PCI.

BACKGROUND: It is unclear whether the beneficial effects of intravascular imaging-guided stent optimization vary by clinical presentation during complex percutaneous coronary intervention (PCI). OBJECTIVES: In this prespecified, stratified subgroup analysis from RENOVATE-COMPLEX-PCI (Randomized Controlled Trial of Intravascular Imaging Guidance versus Angiography-Guidance on Clinical Outcomes After Complex PCI), we sought to compare the outcomes between intravascular imaging vs angiography guidance according to clinical presentation. METHODS: Patients with complex coronary artery lesions were randomly assigned to undergo either intravascular imaging-guided PCI or angiography-guided PCI in a 2:1 ratio. The primary endpoint was target vessel failure (TVF), which is a composite of cardiac death, target vessel-related myocardial infarction, or clinically driven target vessel revascularization. RESULTS: Of 1,639 patients, 832 (50.8%) presented with acute coronary syndrome (ACS) and 807 (49.2%) with chronic coronary syndrome. During a median follow-up of 2.1 years (Q1-Q3: 1.4-3.0 years), there was no significant interaction between the treatment effect of intravascular imaging and clinical presentation (P for interaction = 0.19). Among patients with ACS, the incidences of TVF were 10.4% in the intravascular imaging group and 14.6% in the angiography group (HR: 0.74; 95% CI: 0.48-1.15; P = 0.18). Among patients with CCS, the incidences of TVF were 5.0% in the intravascular imaging group and 10.4% in the angiography group (HR: 0.46; 95% CI: 0.27-0.80; P = 0.006). Achieving stent optimization by intravascular imaging resulted in a reduced risk of TVF among patients with ACS who were randomly assigned to intravascular imaging-guided PCI for complex coronary lesions (optimized vs unoptimized, 6.5% vs 14.1%; HR: 0.49; 95% CI: 0.27-0.87; P = 0.02) but not those with CCS (5.4% vs 4.7%, HR: 1.18; 95% CI: 0.53-2.59; P = 0.69). CONCLUSIONS: No significant interaction was observed between the benefits of intravascular imaging and clinical presentation in the risk of TVF. Stent optimization by intravascular imaging was particularly important for ACS patients. (Intravascular Imaging- Versus Angiography-Guided Percutaneous Coronary Intervention For Complex Coronary Artery Disease [RENOVATE]; NCT03381872).

Complexified synchrony.

The Kuramoto model and its generalizations have been broadly employed to characterize and mechanistically understand various collective dynamical phenomena, especially the emergence of synchrony among coupled oscillators. Despite almost five decades of research, many questions remain open, in particular, for finite-size systems. Here, we generalize recent work [Thümler et al., Phys. Rev. Lett. 130, 187201 (2023)] on the finite-size Kuramoto model with its state variables analytically continued to the complex domain and also complexify its system parameters. Intriguingly, systems of two units with purely imaginary coupling do not actively synchronize even for arbitrarily large magnitudes of the coupling strengths, |K|→∞, but exhibit conservative dynamics with asynchronous rotations or librations for all |K|. For generic complex coupling, both traditional phase-locked states and asynchronous states generalize to complex locked states, fixed points off the real subspace that exist even for arbitrarily weak coupling. We analyze a new collective mode of rotations exhibiting finite, yet arbitrarily large rotation numbers. Numerical simulations for large networks indicate a novel form of discontinuous phase transition. We close by pointing to a range of exciting questions for future research.

Intravascular Imaging-Guided Optimization of Complex Percutaneous Coronary Intervention by Sex: A Subgroup Analysis of the RENOVATE-COMPLEX-PCI Trial.

Importance: There have been heterogeneous results related to sex differences in prognosis after percutaneous coronary artery intervention (PCI) for complex coronary artery lesions. Objective: To evaluate potential differences in outcomes with intravascular imaging-guided PCI of complex coronary artery lesions between women and men. Design, Setting, and Participants: This prespecified substudy evaluates the interaction of sex in the investigator-initiated, open-label, multicenter RENOVATE-COMPLEX-PCI randomized clinical trial, which demonstrated the superiority of intravascular imaging-guided PCI compared with angiography-guided PCI in patients with complex coronary artery lesions. The trial was conducted at 20 sites in Korea. Patients with complex coronary artery lesions undergoing PCI were enrolled between May 2018 and May 2021, and the median (IQR) follow-up period was 2.1 (1.4-3.0) years. Data were analyzed from December 2022 to December 2023. Interventions: After diagnostic coronary angiography, eligible patients were randomly assigned in a 2:1 ratio to receive intravascular imaging-guided PCI or angiography-guided PCI. The choice and timing of the intravascular imaging device were left to the operators' discretion. Main Outcomes and Measures: The primary end point was target vessel failure, defined as a composite of cardiac death, target vessel-related myocardial infarction, or clinically driven target vessel revascularization. Secondary end points included individual components of the primary end point. Results: Of 1639 included patients, 339 (20.7%) were women, and the mean (SD) age was 65.6 (10.2) years. There was no difference in the risk of the primary end point between women and men (9.4% vs 8.3%; adjusted hazard ratio [HR], 1.39; 95% CI, 0.89-2.18; P = .15). Intravascular imaging-guided PCI tended to have lower incidence of the primary end point than angiography-guided PCI in both women (5.2% vs 14.5%; adjusted HR, 0.34; 95% CI, 0.15-0.78; P = .01) and men (8.3% vs 11.7%; adjusted HR, 0.72; 95% CI, 0.49-1.05; P = .09) without significant interaction (P for interaction = .86). Conclusions and Relevance: In patients undergoing complex PCI, compared with angiographic guidance, intravascular imaging guidance was associated with similar reduction in the risk of target vessel failure among women and men. The treatment benefit of intravascular imaging-guided PCI showed no significant interaction between treatment strategy and sex. Trial Registration: ClinicalTrials.gov Identifier: NCT03381872.

Brief guide to RNA sequencing analysis for nonexperts in bioinformatics.

Transcriptome analysis is widely used for current biological research but remains challenging for many experimental scientists. Here, we present a brief but broad guideline for transcriptome analysis, focusing on RNA sequencing, by providing the list of publicly available datasets, tools, and R packages for practical transcriptome analysis. This work will be useful for biologists to perform key transcriptomic analysis with minimum expertise in bioinformatics.

Ferulic Acid Derivatives Ameliorate Intestine Barrier Destruction by Alleviating Inflammatory Responses in Dextran Sulfate Sodium-Induced Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD), a chronic disorder affecting the colon and rectum, involves the overproduction of pro-inflammatory cytokines causing damage to tight junctions (TJ) in the intestinal epithelial cells and chronic inflammation. The current mainstay of treatment, sulfasalazine, often causes adverse effects, thereby necessitating the exploration of alternative herbal medicines with fewer side effects. Portulaca oleracea L. (P. oleracea), a traditional medicinal herb, contains feruloyl amide compounds. We synthesized new compounds by conjugating ferulic acid (FA) with (±)-octopamine. Our study focused on novel FA derivatives that demonstrate protective effects against the intestinal epithelial barrier and inflammatory responses. In lipopolysaccharide-induced cells, C1 and C1a inhibited the production of inflammatory mediators. In Caco-2 cells, these compounds maintained the TJ protein expression, thereby demonstrating their protective effects on the epithelial barrier. In a mouse model of dextran sulfate sodium-induced IBD, a treatment with these compounds ameliorated features including a body weight reduction, colon shortening, an increased disease activity index, and histopathological changes. Furthermore, C1a demonstrated greater efficacy than C1 at the same concentration. These findings suggest that the novel FA derivative (C1a) effectively alleviates clinical signs and inflammatory mediators in IBD, making these compounds potential candidates as natural medicines for the treatment of IBD.

Oleanolic Acid Acetate Alleviates Cisplatin-Induced Nephrotoxicity via Inhibition of Apoptosis and Necroptosis In Vitro and In Vivo.

Cisplatin is a widely used anti-cancer drug for treating solid tumors, but it is associated with severe side effects, including nephrotoxicity. Various studies have suggested that the nephrotoxicity of cisplatin could be overcome; nonetheless, an effective adjuvant drug has not yet been established. Oleanolic acid acetate (OAA), a triterpenoid isolated from Vigna angularis, is commonly used to treat inflammatory and allergic diseases. This study aimed to investigate the protective effects of OAA against cisplatin-induced apoptosis and necroptosis using TCMK-1 cells and a mouse model. In cisplatin-treated TCMK-1 cells, OAA treatment significantly reduced Bax and cleaved-caspase3 expression, whereas it increased Bcl-2 expression. Moreover, in a cisplatin-induced kidney injury mouse model, OAA treatment alleviated weight loss in the body and major organs and also relieved cisplatin-induced nephrotoxicity symptoms. RNA sequencing analysis of kidney tissues identified lipocalin-2 as the most upregulated gene by cisplatin. Additionally, necroptosis-related genes such as receptor-interacting protein kinase (RIPK) and mixed lineage kinase domain-like (MLKL) were identified. In an in vitro study, the phosphorylation of RIPKs and MLKL was reduced by OAA pretreatment in both cisplatin-treated cells and cells boosted via co-treatment with z-VAD-FMK. In conclusion, OAA could protect the kidney from cisplatin-induced nephrotoxicity and may serve as an anti-cancer adjuvant.

Three new phthalide derivatives from culture broth of Dentipellis fragilis and their cytotoxic activities.

Three new phthalide derivatives (1‒3) together with two known compounds, erinaceolactone B (4) and hericerin III (5), were isolated from the culture broth of Dentipellis fragilis. The chemical structures of 1‒5 were determined by analyses of their 1D-, 2D-NMR, and MS. The absolute configuration of 1 was determined by CD analysis. The isolated compounds were assessed for their cytotoxic activities against A549, DU145, HCT116, and HT1080 cancer cell lines. Compounds 1‒5 showed strong cytotoxic activities against DU145, with IC50 values ranging from 14.3 to 16.1 µM. Additionally, all compounds showed moderate or weak cytotoxic activities against all cell lines except for compounds 4 and 1 which showed no cytotoxic activities against A549 and HCT116 cancer cell lines, respectively. Against HT1080 cancer cell line, only compound 2 displayed moderate cytotoxic activity.

Bakuchicin alleviates ovalbumin-induced allergic asthma by regulating M2 macrophage polarization.

OBJECTIVE: Asthma is an airway inflammatory disease caused by activation of numerous immune cells including macrophages. Bakuchicin (BKC) is known to exhibit anti-inflammatory effects and type 2 T helper (Th2) regulation, but has not been investigated for airway inflammation. This study aimed to evaluate the effects of BKC on airway inflammation and demonstrate the mechanisms of macrophage polarization. METHODS: The anti-inflammatory effects were determined using lipopolysaccharide (LPS)-stimulated macrophages. The ovalbumin (OVA)-induced asthma mouse model was used to evaluate the effects of BKC on airway inflammation and Th2 responses. Moreover, the effect of BKC on macrophage polarization was confirmed in bone marrow-derived macrophages (BMDMs) differentiation. RESULTS: BKC suppressed nitric oxide production and expression of pro-inflammatory cytokines by inhibiting signaling pathway in LPS-stimulated macrophages. In an OVA-induced asthma model, BKC treatment alleviated histological changes and mast cell infiltration and reduced the levels of eosinophil peroxidase, ß-hexosaminidase, and immunoglobulin levels. In addition, BKC alleviated Th2 responses and M2 macrophage populations in bronchoalveolar fluid. In BMDMs, BKC suppressed IL-4-induced M2 macrophage polarization and the expression of M2 markers such as arginase-1 and Fizz-1 through inhibiting sirtuin 2 levels. CONCLUSION: BKC could be a drug candidate for the treatment of allergic asthma.

Multitemporal analysis of land subsidence induced by open-pit mining activity using improved combined scatterer interferometry with deep learning algorithm optimization.

Mine operational safety is an important aspect of maintaining the operational continuity of a mining area. In this study, we used the InSAR time series to analyze land surface changes using the ICOPS (improved combined scatterers with optimized point scatters) method. This ICOPS method combines persistent scatterers (PS) with distributed scatterers (DS) to increase surface deformation analysis's spatial coverage and quality. One of the improvements of this study is the use of machine learning in postprocessing, based on convolutional neural networks, to increase the reliability of results. This study used data from the Sentinel-1 SAR C-band satellite during the 2016-2022 observation period at the Musan mine, North Korea. In the InSAR surface deformation time analysis, the maximum average rate of land subsidence was approximately > 15.00 cm per year, with total surface deformation of 170 cm and 70 cm for the eastern dumping area and the western dumping area, respectively. Analyzing the mechanism of land surface changes also involved evaluating the geological conditions in the Musan mining area. Our research findings show that combining machine learning and statistical methods has great potential to enhance the understanding of mine surface deformation.

Combinatorial transcriptomic and genetic dissection of insulin/IGF-1 signaling-regulated longevity in Caenorhabditis elegans.

Classical genetic analysis is invaluable for understanding the genetic interactions underlying specific phenotypes, but requires laborious and subjective experiments to characterize polygenic and quantitative traits. Contrarily, transcriptomic analysis enables the simultaneous and objective identification of multiple genes whose expression changes are associated with specific phenotypes. Here, we conducted transcriptomic analysis of genes crucial for longevity using datasets with daf-2/insulin/IGF-1 receptor mutant Caenorhabditis elegans. Our analysis unraveled multiple epistatic relationships at the transcriptomic level, in addition to verifying genetically established interactions. Our combinatorial analysis also revealed transcriptomic changes associated with longevity conferred by daf-2 mutations. In particular, we demonstrated that the extent of lifespan changes caused by various mutant alleles of the longevity transcription factor daf-16/FOXO matched their effects on transcriptomic changes in daf-2 mutants. We identified specific aging-regulating signaling pathways and subsets of structural and functional RNA elements altered by different genes in daf-2 mutants. Lastly, we elucidated the functional cooperation between several longevity regulators, based on the combination of transcriptomic and molecular genetic analysis. These data suggest that different biological processes coordinately exert their effects on longevity in biological networks. Together our work demonstrates the utility of transcriptomic dissection analysis for identifying important genetic interactions for physiological processes, including aging and longevity.