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To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.cell.2005.02.030 Byline: Meng C. Wang (1), Dirk Bohmann (1), Heinrich Jasper (1) Abstract: Aging of a eukaryotic organism is affected by its nutrition state and by its ability to prevent or repair oxidative damage. Consequently, signal transduction systems that control metabolism and oxidative stress responses influence life span. When nutrients are abundant, the insulin/IGF signaling (IIS) pathway promotes growth and energy storage but shortens life span. The transcription factor Foxo, which is inhibited by IIS, extends life span in conditions of low IIS activity. Life span can also be increased by activating the stress-responsive Jun-N-terminal kinase (JNK) pathway. Here we show that JNK requires Foxo to extend life span in Drosophila. JNK antagonizes IIS, causing nuclear localization of Foxo and inducing its targets, including growth control and stress defense genes. JNK and Foxo also restrict IIS activity systemically by repressing IIS ligand expression in neuroendocrine cells. The convergence of JNK signaling and IIS on Foxo provides a model to explain the effects of stress and nutrition on longevity. Author Affiliation: (1) Department of Biomedical Genetics, The Aab Institute of Biomedical Sciences, University of Rochester Medical Center, 601 Elmwood Avenue, Box 633, Rochester, New York 14642 Article History: Received 8 November 2004; Revised 20 January 2005; Accepted 28 February 2005 Article Note: (miscellaneous) Published online: March 24, 2005

The tensile behavior at elevated temperature of heavily plastically deformed Al-Mg alloys with an Mg content of 1 to 5% was investigated. Large plastic deformation was imposed by confined channel die pressing at room temperature up to 18 passes. During heating to test temperature the specimens were observed to undergo recovery and partly recrystallization. The strain rate sensitivity was found to increase with increasing test temperature, and the previously reported asymmetry of the stress differential upon instantaneous up and down strain rate changes disappeared at elevated temperatures. The transition temperature from the low temperature to the high temperature behavior depended on the amount of pre-deformation. The observed phenomena were attributed to a change in deformation mechanism which occurred the earlier, i.e. at lower temperature, the higher the dislocation density introduced by pre-deformation. Image, graphical abstract [ABSTRACT FROM AUTHOR]

High hepatitis B virus (HBV) DNA level is strongly associated with hepatocellular carcinoma (HCC) development in chronic HBV infection. The aim of this study was to investigate the association between intrahepatic HBV DNA titer and post-liver transplantation (LT) prognosis for HBV-related HCC (HBV-HCC) patients. A total of 60 patients with HBV-HCC who underwent LT were retrospectively studied. Using quantitative TaqMan fluorescent real-time polymerase chain reaction assay, HBV total DNA (tDNA) and covalently closed circular DNA (cccDNA) were both quantified in tumor tissue (TT) and adjacent non-tumor tissue (ANTT) from the explanted liver. The loads of tDNA and cccDNA in ANTT were associated with serum HBV DNA levels. Multivariate analysis showed that the presence of vascular invasion and cccDNA in TT were independent risk factors for tumor recurrence. The group of patients with cccDNA titers ≥31og l0 copies/μg in TT had significantly higher cumulative recurrence rates than those with <31og l0 copies/μg group. The cccDNA titers predicted the tumor recurrence with an area under the receiver operating characteristic curve of 0.664. Our findings would assist the clinical implementation of a more personalized therapy for tumor recurrence control and improve the prognosis of HBV-HCC patients. • cccDNA titer (≥31og l0 copies/μg) in the tumor tissue may predispose patients to HCC recurrence after liver transplantation in HBV-HCC patients. [ABSTRACT FROM AUTHOR]

Background Hyperparathyroidism is a common complication in chronic kidney disease and might persist in up to 25% of patients after transplantation. In this setting, vitamin D analogues further aggravate persistent hypercalcemia and cinacalcet has not been approved for these patients, some of whom will require parathyroidectomy to correct post-transplantation hyperparathyroidism. Objectives In this single-center, retrospective study we aimed to analyze the long-term effect of parathyroidectomy on calcium, phosphorus, and parathyroid hormone (PTH) levels and its effect on allograft function in kidney transplantation patients submitted to parathyroidectomy. Patients and Methods Fifteen patients underwent parathyroidectomy between January 2005 and January 2015; median age 54 years old; 8 (53.3%) were receiving cinacalcet at the time of surgery. Pre-parathyroidectomy median values of intact PTH, calcium, and phosphorus were, respectively, 262 pg/mL, 10.8 mg/dL, and 2.4 mg/dL. Surgery consisted of uniglandular parathyroidectomy in 5 (33.3%) patients, biglandular in 4 (26.7%), and subtotal in 6 (40%). There was no surgery-related mortality. Results Compared with baseline, there was a decrease of PTH (262 pg/mL vs. 106 pg/mL, P = .001), calcium, and phosphorus levels (10.8 mg/dL vs. 10.4 mg/dL, P = .3; 2.4 vs. 2.9 mg/dL, P = .05) 1 year after surgery; with normalization of serum calcium at the end of follow-up (10.8 mg/dL vs. 9.4 mg/dL, P = .04). A decrease in estimated glomerular filtration rate occurred 1 month post-surgery (62.7 mL/m vs. 49.7 mL/m, P = .006) but returned to baseline 1 year after surgery (62.7 mL/m vs. 60.8 mL/m, P = .73). Conclusion Parathyroidectomy appears to be a safe procedure and should be considered in kidney transplantation patients with persistent post-transplantation hyperparathyroidism. Although there was an acute estimated glomerular filtration rate decrease, we observed no long-term deterioration in allograft function. [ABSTRACT FROM AUTHOR]

Purpose: To determine whether localized hyperosmotic spikes on the pre-lens tear film (PrLTF) due to tear break up results in hyperosmotic spikes on the ocular surface during soft-contact-lens (SCL) wear and whether wear of SCLs can protect the cornea against PrLTF osmotic spikes.Methods: Two-dimensional transient diffusion of salt was incorporated into a computationally designed SCL, post-lens tear film (PoLTF), and ocular surface and solved numerically. Time-dependent localized hyperosmolarity spikes were introduced at the anterior surface of the SCL corresponding to those generated in the PrLTF. Salt spikes were followed in time until spikes penetrate through the lens into the PoLTF. Lens-salt diffusivities (Ds) were varied to assess their importance on salt migration from the PrLTF to the ocular surface. SCL and PoLTF initial conditions and the lens anterior-surface boundary condition were varied depending on the value of Ds and on dry-eye symptomatology. Determined corneal surface osmolarities were translated into clinical pain scores.Results: For Ds above about 10-7cm2/s, it takes around 5-10 s for the PrLTF hyperosmotic break-up spikes to diffuse across the SCL and reach the corneal surface. Even if localized hyperosmotic spikes penetrate to the ocular surface, salt concentrations there are much lower than those in the progenitor PrLTF spikes. For Ds less than 10-7cm2/s, the SCL protects the cornea from hyperosmotic spikes for both normal and dry eyes. When localized corneal hyperosmolarity is converted into transient pain scores, pain thresholds are significantly lower than those for no-lens wear.Conclusions: A cornea can be protected from localized PrLTF hyperosmolarity spikes with SCL wear. With regular blinking (e.g., less than 10 s), SCL wear shields the cornea from significant hyperosmotic pain. Decreasing Ds increases that protection. Low-Ds soft contact lenses can protect against hyperosmotic spikes and discomfort even during infrequent blinking (e.g., > 10 s). [ABSTRACT FROM AUTHOR]

Interleukin-6 (IL-6) has been shown to promote post-stroke angiogenesis and long-term functional recovery; however, whether IL-6 could promote post-stroke neurogenesis remains unclear. This study aims to investigate the effects of IL-6 on neurogenesis after ischemic stroke. We also investigated whether pair housing (PH) could improve the experimental stroke outcome through IL-6. Transient middle cerebral artery occlusion (tMCAO) was induced in mice treated with recombinant IL-6 (rIL-6) or anti-IL-6 neutralizing antibodies (anti-IL-6 mAbs). Another set of mice were pair-housed (PH; male and ovariectomized female) for 2 weeks, subjected to tMCAO and then assigned to a housing condition (isolated or PH). Pair-housed mice were treated with anti-IL-6 mAbs. Behavioral assessments were made 3 days before tMCAO and after 28 days of reperfusion. Neural progenitor cells (NPCs) isolated from ipsilateral subventricular zone (SVZ) at 14 days post-ischemia were treated with rIL-6 plus soluble IL-6 receptor (sIL-6R). The effects of IL-6 on the proliferation and differentiation of NPCs were examined in vivo and in vitro . The role and mechanism of IL-6 in PH-mediated enhancement of NPC proliferation and functional recovery were investigated in vivo . We found that anti-IL-6 mAbs significantly reduced the proliferation and neuronal differentiation of NPCs in the ipsilateral SVZ, as well as functional recovery; whereas rIL-6 conferred the opposite effects. PH significantly promoted NPC proliferation and functional recovery compared with socially isolated cohorts; blockade of IL-6 with anti-IL-6 mAbs prevented this promoting effect. In conclusion, our results suggest that IL-6 is an important mediator of social interaction on neurogenesis and long-term functional recovery after ischemic stroke. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the influence of lens care solutions (LCS) on interfacial dynamics and rheological properties of human tear-lipid films. Methods: Tear lipids were extracted from Schirmer strips collected from 6 healthy subjects. Sessile bubble tensiometry was used to study interfacial properties at 22 °C. Lipids were deposited on an air bubble immersed into electrolytes solution to form 90 ± 20 nm films. Lipid films were subjected to expansion-compression cycles for dynamic interfacial properties and to step-strain relaxations for assessments of rheological properties. LCS (BioTrue [BT], PureMoist [PM], Revitalens [RL], ClearCare [CC]) were injected into optical chamber and equilibrated for 2 h without or with lipid films. Dynamic interfacial properties of films were measured. Then electrolyte solution was pumped through chamber and properties of films were re-evaluated. Results: Equilibrium surface tension (EST), elasticity modulus (E), and relaxation times (τ) of tear lipids were 22 ± 2.1 mN/m, 10.7-14.8 mN/m, and 80-150 s, respectively. EST for LCS was 45.3 ± 0.8 for CC, 40.3 ± 0.8 for BT, 33.4 ± 1.0 for PM, and 30.1 ± 0.8 mN/m for RL. E for LCS varied within 0.5-6.7 mN/m, and τ varied from 49 to 68 ± 5 s. For mixed lipids + LCS films, EST remained unchanged whereas E and τ were reduced for all LCS types. Exposure to PM and RL noticeably altered the shape of lipid-film iso-cycles. These changes persisted after LCS washout. Conclusions: Some components of LCS bind irreversibly to lipid films and make them less viscous and less elastic. These findings suggest the possibility of tear-film destabilization upon LCS exposure. [ABSTRACT FROM AUTHOR]

Purpose: With active investigation underway for embedded-circuit contact lenses, safe oxygen supply of these novel lenses remains a question. Central-to-peripheral corneal edema for healthy eyes during wear of soft contact (SCL) and scleral lenses (SL) with embedding components is assessed.Methods: Various 2-dimensional (2D) designs of SL and SCL with embedded components are constructed on Comsol Multiphysics 5.5. Local corneal swelling associated with the designed lenses is determined by a recently developed 2D metabolic-swelling model. Settled central post-lens tear-film thicknesses (PoLTFs) are set at 400 μm and 3 μm for SL and SCL designs, respectively. Each lens design has an axisymmetric central and an axisymmetric peripheral embedment. Oxygen permeability (Dk) of the lens and the embedments ranges from 0 to 200 Barrer. Dimensions and location of the embedments are varied to assess optimal-design configurations to minimize central-to-peripheral corneal edema.Results: By adjusting oxygen Dk of the central embedment, the peripheral embedment, or the lens matrix polymer, corneal swelling is reduced by up to 2.5 %, 1.5 %, or 1.4 % of the baseline corneal thickness, respectively, while keeping all other parameters constant. A decrease in PoLTF thickness from 400 μm to 3 μm decreases corneal edema by up to 1.8 % of the baseline corneal thickness. Shifting the peripheral embedment farther out towards the periphery and towards the anterior lens surface reduces peak edema by up to 1.3 % and 0.6 % of the baseline corneal thickness, respectively.Conclusions: To minimize central-to-peripheral corneal edema, embedments should be placed anteriorly and far into the periphery to allow maximal limbal metabolic support and oxygen transport in the polar direction (i.e., the θ-direction in spherical coordinates). High-oxygen transmissibility for all components and thinner PoLTF thickness are recommended to minimize corneal edema. Depending on design specifications, less than 1 % swelling over the entire cornea is achievable even with oxygen-impermeable embedments. [ABSTRACT FROM AUTHOR]

Abstract: Background and aims: The brachial-ankle pulse wave velocity (baPWV) is a marker for early atherosclerotic changes. Serum total bilirubin (TB) is an effective antioxidant and has been associated with carotid intima-media thickness, cardiovascular disease, stroke and peripheral arterial disease, all of which may be caused by arteriosclerosis. This study aimed to investigate the association of TB with arterial stiffness. Methods and results: In this cross-sectional study, we investigated the relationship between TB and baPWV in 2207 participants (1331 men, 876 women) in a general health examination. Different metabolic parameters were compared across TB quartiles. Age-adjusted mean values of baPWV gradually decreased with TB quartiles in men (Q1 = 1348, Q2 = 1266, Q3 = 1215, and Q4 = 1154 cm/s). However, the age-adjusted means of baPWV had no significance in women according to TB quartiles. Univariate analysis showed that age, smoking status, BMI, SBP, DBP, AST, ALT, GGT, TB, TG, and HDL-C were significantly associated with baPWV in men, whereas only age, BMI, SBP, DBP, TG and FPG were significantly associated with baPWV in women. In addition, BMI, SBP, TB, age, TG, and AST were significant factors in the multivariate model with baPWV in men; only BMI and FPG were significant factors with baPWV in women. Conclusion: The findings show that serum total bilirubin concentration is negatively correlated to arterial stiffness in Chinese men. Early detection of abnormal bilirubin levels could potentially serve as an early biomarker for arterial stiffness. [Copyright &y& Elsevier]

Abstract: Intense muon beams have very important applications by using μSR techniques and other methods. An experimental muon source (EMuS) as a parasitic facility at China Spallation Neutron Source (CSNS) is proposed. EMuS makes use of a small portion of the high power proton beam from the CSNS accelerator complex. It will provide an excellent platform for muon beam based multidisciplinary research, and will also serve as the development base for a future full-scale muon source at CSNS. The available proton beam power of 4kW at 1.6GeV can produce intense muon flux with a thick production target. The muon yields with different target materials and shapes, and the muon collection efficiency have been simulated by using the FLUKA code. It is found that the graphite target of about 10–12cm in thickness and rectangular in cross-section is a good choice, and that the collection at 90° from the beam direction is the best for surface muons. It is found that 4-D emittance volume instead of two independent 2-D emittances should be used to define the relation between the optimal muon intensity and the muon channel acceptance, due to the asymmetry between the distributions in the two transverse phase planes. The collected muon intensities for both surface muons and cloud muons with different emittances have also been studied, which are important for designing the muon beam transport line. The intensities of positive and negative muons are in the orders of 105 μ+/s and 104 μ−/s, respectively. [Copyright &y& Elsevier]

Abstract: JNK signaling functions to induce defense mechanisms that protect organisms against acute oxidative and xenobiotic insults. Using Drosophila as a model system, we investigated the role of autophagy as such a JNK-regulated protective mechanism. We show that oxidative stress can induce autophagy in the intestinal epithelium by a mechanism that requires JNK signaling. Consistently, artificial activation of JNK in the gut gives rise to an autophagy phenotype. JNK signaling can induce the expression of several autophagy-related (ATG) genes, and the integrity of these genes is required for the stress protective function of the JNK pathway. In contrast to autophagy induced by oxidative stress, non-stress related autophagy, as it occurs for example in starving adipose or intestinal tissue, or during metamorphosis, proceeds independently of JNK signaling. Autophagy thus emerges as a multifunctional process that organisms employ in a variety of different situations using separate regulatory mechanisms. [Copyright &y& Elsevier]

Changes in the genetic makeup of an organism can extend lifespan significantly if they promote tolerance to environmental insults and thus prevent the general deterioration of cellular function that is associated with aging. Here, we introduce the Jun N-terminal kinase (JNK) signaling pathway as a genetic determinant of aging in Drosophila melanogaster. Based on expression profiling experiments, we demonstrate that JNK functions at the center of a signal transduction network that coordinates the induction of protective genes in response to oxidative challenge. JNK signaling activity thus alleviates the toxic effects of reactive oxygen species (ROS). In addition, we show that flies with mutations that augment JNK signaling accumulate less oxidative damage and live dramatically longer than wild-type flies. Our work thus identifies the evolutionarily conserved JNK signaling pathway as a major genetic factor in the control of longevity. [Copyright &y& Elsevier]

Contact lens extended wear increases the permeability of epithelium to sodium fluorescein (Pdc). The exact mechanism is not known. However, changes in Pdc likely result from either corneal hypoxia or mechanical trauma, or both. We explored the effects of one-night continuous wear with either high- or low-Dk/t soft lenses on Pdc. The results show that corneal epithelial barrier function decreases significantly with both lens groups. We also observed that Asian eyes had higher Pdc after overnight wear compared to non-Asian and that for both Asian and non-Asian eyes, the elimination of corneal hypoxia did not prevent changes in epithelial permeability. [Copyright &y& Elsevier]

Initial results from the Active Plasma EXperiment North Star experiment are presented. The North Star active experiment included two separate plasma jet injections, both perpendicular to the Earth''s magnetic field. The objective of the experiment is to investigate the interaction of high-speed (7–40 km/s) plasma jets with the ionospheric plasma and the coupling to the magnetosphere and lower ionosphere. The plasma jets were produced using an Explosive Type Generator device. This device is a shaped-charge device that vaporizes porous aluminum inside the generator and forces the vaporized products out of a nozzle, resulting in the production of a high-speed, partially ionized aluminum plasma jet. Instrumentation on three different payloads was used to obtain multi-point observations of the plasma jet properties, optical radiation from the jets, and ionospheric perturbations. Imagery, high-speed photometry, and spectrographic imagery using ground- and space-based sensors were used to monitor the dynamics and spectral content of the plasma jet. This paper describes the experiment and summarizes the initial results from the North Star experiment. [Copyright &y& Elsevier]

Dear Editor, We read with interest the recent manuscript by Fisher et al. [1] entitled "Fluid reservoir thickness and corneal oedema during closed eye scleral lens wear", that reports closed-eye central corneal edema after 90-min wear of scleral lenses (SL). The metabolic-edema theory of Kim et al. [2] assesses open-eye and overnight SL-wear swelling for settled PoLTF thicknesses between 50 and 400 m and for lens-oxygen transmissibilities from 0 to 100 hBarrer/cm. References 1 D. Fisher, M.J. Collins, S.J. Vincent, Fluid reservoir thickness and corneal oedema during closed eye scleral lens wear. [Extracted from the article]

This study aimed to investigate the association between depressive symptoms and diet- and lifestyle-related behaviors among adolescents. Cross-sectional study. Our study used stratified random cluster sampling method to recruit 6,251 adolescents aged 11–19 years as samples for research and analysis. The Center for Epidemiological Studies Depression Scale was used to assess depressive symptoms. Chi-squared test, t test, and logistic regression were used to explore the diet and lifestyle factors of depressive symptoms. Backpropagation (BP) neural network model was used to investigate the ranking of diet and lifestyle behaviors factors of depressive symptoms. The prevalence of depressive symptoms among adolescents was 32.1%. Multivariable logistic regression was used to determine 10 important variables of depressive symptoms. After ranking the importance by BP neural network, the top three important variables were found, which were sleep duration (100%), screen time (49.1%), and breakfast (23.6%). Sleep duration, screen time, and breakfast were associated factors with the most significant impacts on depressive symptoms. [ABSTRACT FROM AUTHOR]

• A new methodology for long-term evaporation evaluation is developed. • A slow water-evaporation through human and model lipid films in vitro is verified. • Evaporation in vitro reduces as lipid nanofilms mature to form specific structures. • Saturated phospholipids enhance evaporation reductions by mixed lipid films. • The similarity between model lipids and human tear-lipids interfacial rheology is achieved. A novel methodology for assessing evaporation (up to 48 h) through lipid-nanofilms in vitro was developed. The influence of lipid-mixture compositions on evaporation rates was studied. The evaporative fluxes and rheology of lipid-nanofilms were compared with those of human tear-lipid nanofilms in vitro.A sessile-drop technique with precise drop-volume control was adapted to measure evaporation rates at constant temperature of 36 °C and humidity of 75 %. Model lipid solutions were deposited on the surface of aqueous drops to create nanofilms of 10–100 nm. The measurements of dynamic surface pressure vs. nanofilm-thickness were performed under the same conditions. The lipid-mixtures compositions were chosen to mimic that of human tear lipids. Evaporation through lipid nanofilms decreased with film thickness and aging. Evaporation through 70-nm films was 2.5–3 time slower than through 10-nm-thick films. Nonpolar-lipid mixtures reduced evaporation by approximately 35 %. The optimized model-lipid mixtures containing polar phospholipids reduced evaporation by 70–75 %, matching the evaporation-reduction by human-lipid nanofilms in vitro. These model mixtures exhibited interfacial rheology similar to human tear lipids in vitro.This methodology substantiated that aged lipid-nanofilms significantly reduced evaporation in vitro. These findings contradict to the previous reports suggesting that model lipid and meibum films do not retard evaporation in vitro. Polar phospholipids enhance evaporative resistance close to the level observed for human tear-lipid films in vivo. We hypothesize that unique rheological properties of tear-lipid nanofilms are germane to the specific mono- and bi-layered structures formed by phospholipids at the lipid-air and lipid-aqueous interfaces. [ABSTRACT FROM AUTHOR]

Lipids play crucial roles in regulating aging and longevity. In the past few decades, a series of genetic pathways have been discovered to regulate lifespan in model organisms. Interestingly, many of these regulatory pathways are linked to lipid metabolism and lipid signaling. Lipid metabolic enzymes undergo significant changes during aging and are regulated by different longevity pathways. Lipids also actively modulate lifespan and health span as signaling molecules. In this review, we summarize recent insights into the roles of lipid metabolism and lipid signaling in aging and discuss lipid-related interventions in promoting longevity. Lipid metabolic enzymes undergo significant changes during aging and are regulated by different longevity pathways. Mutlu et al. present a review about the role lipids play in regulating aging and longevity, including the regulatory pathways linked to lipid metabolism and lipid signaling and how lipids modulate lifespan as signaling molecules. [ABSTRACT FROM AUTHOR]

Lysosomes transcend the role of degradation stations, acting as key nodes for interorganelle crosstalk and signal transduction. Lysosomes communicate with the nucleus through physical proximity and functional interaction. In response to external and internal stimuli, lysosomes actively adjust their distribution between peripheral and perinuclear regions and modulate lysosome–nucleus signaling pathways; in turn, the nucleus fine-tunes lysosomal biogenesis and functions through transcriptional controls. Changes in coordination between these two essential organelles are associated with metabolic disorders, neurodegenerative diseases, and aging. In this review, we address recent advances in lysosome–nucleus communication by multi-tiered regulatory mechanisms and discuss how these regulations couple metabolic inputs with organellar motility, cellular signaling, and transcriptional network. Lysosomal–nuclear communication coordinates lysosomal positioning, metabolism, and signaling with nuclear transcription to support fundamental cellular activities. Lysosomal positioning between peripheral and perinuclear regions is subject to cooperative regulation in response to metabolic stimuli and contributes to lysosomal functions and signaling. Retrograde transport of chaperone proteins and transcription factors from the lysosome to the nucleus is actively regulated by metabolic signaling. Nuclear transcriptional networks comprise a variety of different transcription factors that act independently or coordinately to fine tune lysosomal-autophagic gene expression. [ABSTRACT FROM AUTHOR]

Lysosomes are sites of active metabolism in a cell. They contain various hydrolases that degrade extracellular and intracellular materials during endocytosis and autophagy, respectively. In addition to their long-recognized roles in degradation and recycling, emerging studies have revealed that lysosomes are organizing centers for signal transduction. Lysosome-derived signaling plays crucial roles in regulating nutrient sensing, metabolic adaptation, organelle crosstalk, and aging. In particular, how the degradative role of the lysosome cooperates with its signaling functions to actively modulate lifespan is beginning to be unraveled. This review describes recent advances in the role of the lysosome as a 'signaling hub' that uses three different lysosome-derived signaling pathways to integrate metabolic inputs, organelle interactions, and the control of longevity. The lysosome serves as a signaling center to integrate extracellular and intracellular inputs, and accordingly regulates cellular homeostasis and organism fitness. mTORC1 at the lysosomal surface responds to amino acid and cholesterol signals from the lysosomal lumen, and coordinates downstream pathways involved in aging control. AMPK is recruited to the lysosomal surface for activation in response to glycolytic signals, and promotes longevity via specific downstream effectors. Specific lipid messengers and chaperones mediate lysosome-to-nucleus retrograde signaling communication to improve interorganelle crosstalk, redox homeostasis, and longevity. [ABSTRACT FROM AUTHOR]