Translational control in cell ageing: an update

Cellular ageing is one of the main drivers of organismal ageing and holds keys towards improving the longevity and quality of the extended life. Elucidating mechanisms underlying the emergence of the aged cells as well as their altered responses to the environment will help understanding the evolutionarily defined longevity preferences across species with different strategies of survival. Much is understood about the role of alterations in the DNA, including many epigenetic modifications such as methylation, in relation to the aged cell phenotype. While transcriptomes of the aged cells are beginning to be better-characterised, their translational responses remain under active investigation. Many of the translationally controlled homeostatic pathways are centred around mitigation of DNA damage, cell stress response and regulation of the proliferative potential of the cells, and thus are critical for the aged cell function. Translation profiling-type studies have boosted the opportunities in discovering the function of protein biosynthesis control and are starting to be applied to the aged cells. Here, we provide a summary of the current knowledge about translational mechanisms considered to be commonly altered in the aged cells, including the integrated stress response-, mechanistic target of Rapamycin- and elongation factor 2 kinase-mediated pathways. We enlist and discuss findings of the recent works that use broad profiling-type approaches to investigate the age-related translational pathways. We outline the limitations of the methods and the remaining unknowns in the established ageing-associated translation mechanisms, and flag translational mechanisms with high prospective importance in ageing, for future studies.

Study of the Extraction Efficiency of Cathode Material and Its Structural Stability after Extraction

Extraction of the cathode material from disassembled Samsung 18650 cell with LiCoO2 (LCO) chemistry was performed. The effect of dissolving with industrially used organic solvents is compared with the effect of selected ecological options. In successfully separated powders were studied structural changes as a function of aging and storage time. Ex-situ X-ray diffraction analysis was used for observation of differences between materials separated from cell in a fresh state and aged cell. Phase transition happening in the LiCoO2 material during cycling of the battery but also when in contact with air are discussed. Shift of the main peak (0 0 3) and (1 0 4) for the aged cathode material are displayed and discussed.

Aging Behavior of Lithium Titanate Battery under High-Rate Discharging Cycle

The high-rate discharging performance of a lithium titanate battery is one of its main properties. In conditions that require ultra-high-rate discharging, a lithium titanate battery can be discharged continuously at a current of 50 C (50 times of its maximum capacity) or higher. In this paper, we take cylindrical steel shell lithium titanate cells as the research object and perform aging cycles at 66 C on these cells. The ultra-high-rate discharging cycles cause a rapid high-power capacity fading while the available capacity at normal current rate is not affected. The capacity at 66 C decreases to 80% of initial value in 10 cycles. This paper also analyzes the aging process of a lithium titanate battery at high-rate discharging with incremental capacity (IC) analysis, and presents the aging behavior of lithium titanate battery qualitatively, which is inconsistent with existing research. We attribute the aging mechanism of ultra-high-rate discharging cycles to the decrease of ionic mobility and increase of polarization resistance. Mechanical damage is observed in the CT scan of an aged cell, which we presume to be the result of rapid strain of cathode material.

Transmigration of Neutrophils From Patients With Familial Mediterranean Fever Causes Increased Cell Activation

Familial Mediterranean fever (FMF) is caused by pyrin-encoding MEFV gene mutations and characterized by the self-limiting periods of intense inflammation, which are mainly mediated by a massive influx of polymorphonuclear neutrophils (PMNs) into the inflamed sites. Perturbation of actin polymerization by different pathogens was shown to activate the pyrin inflammasome. Our aim was to test whether cytoskeletal dynamics in the absence of pathogens may cause abnormal activation of PMNs from FMF patients. We also aimed to characterize immunophenotypes of circulating neutrophils and their functional activity. Circulating PMNs displayed heterogeneity in terms of cell size, granularity and immunophenotypes. Particularly, PMNs from the patients in acute flares (FMF-A) exhibited a characteristic of aged/activated cells (small cell size and granularity, up-regulated CXCR4), while PMNs form the patients in remission period (FMF-R) displayed mixed fresh/aged cell characteristics (normal cell size and granularity, up-regulated CD11b, CD49d, CXCR4, and CD62L). The findings may suggest that sterile tissue-infiltrated PMNs undergo reverse migration back to bone marrow and may explain why these PMNs do not cause immune-mediated tissue damage. A multidirectional expression of FcγRs on neutrophils during acute flares was also noteworthy: up-regulation of FcγRI and down-regulation of FcγRII/FcγRIII. We also observed spontaneous and fMPL-induced activation of PMNs from the patients after transmigration through inserts as seen by the increased expression of CD11b and intracellular expression of IL-1β. Our study suggests heightened sensitivity of mutated pyrin inflammasome towards cytoskeletal modifications in the absence of pathogens.

Identifying the Degradation Mechanism in Commercial Lithium Rechargeable Batteries via High-Energy X-ray Compton Scattering Imaging

Synchrotron-based high-energy X-ray Compton scattering imaging is a promising technique for non-destructively and quantitatively investigating commercialized lithium rechargeable batteries. We apply the Compton scattering imaging technique to commercial coin-type lithium rechargeable cells (VL2020) to non-destructively identify the degradation mechanism of the cell. The correlations between the Compton scattering intensity and line-shape of the Compton scattering X-ray energy spectrum (S-parameter) obtained from this technique produce unique distributions that characterize the aged cell. These distributions in the aged cell indicate that the stable phase of the anode formed through the overvoltage charge–discharge cycle. This stable phase prevents lithium reactions, producing microbubbles with the decomposition of the electrolyte.

Proteasome Activation to Combat Proteotoxicity

Loss of proteome fidelity leads to the accumulation of non-native protein aggregates and oxidatively damaged species: hallmarks of an aged cell. These misfolded and aggregated species are often found, and suggested to be the culpable party, in numerous neurodegenerative diseases including Huntington’s, Parkinson’s, Amyotrophic Lateral Sclerosis (ALS), and Alzheimer’s Diseases (AD). Many strategies for therapeutic intervention in proteotoxic pathologies have been put forth; one of the most promising is bolstering the efficacy of the proteasome to restore normal proteostasis. This strategy is ideal as monomeric precursors and oxidatively damaged proteins, so called “intrinsically disordered proteins” (IDPs), are targeted by the proteasome. This review will provide an overview of disorders in proteins, both intrinsic and acquired, with a focus on susceptibility to proteasomal degradation. We will then examine the proteasome with emphasis on newly published structural data and summarize current known small molecule proteasome activators.

Mitochondria-Targeting Antioxidant Provides Cardioprotection through Regulation of Cytosolic and Mitochondrial Zn2+ Levels with Re-Distribution of Zn2+-Transporters in Aged Rat Cardiomyocytes

Aging is an important risk factor for cardiac dysfunction. Heart during aging exhibits a depressed mechanical activity, at least, through mitochondria-originated increases in ROS. Previously, we also have shown a close relationship between increased ROS and cellular intracellular free Zn2+ ([Zn2+]i) in cardiomyocytes under pathological conditions as well as the contribution of some re-expressed levels of Zn2+-transporters for redistribution of [Zn2+]i among suborganelles. Therefore, we first examined the cellular (total) [Zn2+] and then determined the protein expression levels of Zn2+-transporters in freshly isolated ventricular cardiomyocytes from 24-month rat heart compared to those of 6-month rats. The [Zn2+]i in the aged-cardiomyocytes was increased, at most, due to increased ZIP7 and ZnT8 with decreased levels of ZIP8 and ZnT7. To examine redistribution of the cellular [Zn2+]i among suborganelles, such as Sarco/endoplasmic reticulum, S(E)R, and mitochondria ([Zn2+]SER and [Zn2+]Mit), a cell model (with galactose) to mimic the aged-cell in rat ventricular cell line H9c2 was used and demonstrated that there were significant increases in [Zn2+]Mit with decreases in [Zn2+]SER. In addition, the re-distribution of these Zn2+-transporters were markedly changed in mitochondria (increases in ZnT7 and ZnT8 with no changes in ZIP7 and ZIP8) and S(E)R (increase in ZIP7 and decrease in ZnT7 with no changes in both ZIP8 and ZnT8) both of them isolated from freshly isolated ventricular cardiomyocytes from aged-rats. Furthermore, we demonstrated that cellular levels of ROS, both total and mitochondrial lysine acetylation (K-Acetylation), and protein-thiol oxidation were significantly high in aged-cardiomyocytes from 24-month old rats. Using a mitochondrial-targeting antioxidant, MitoTEMPO (1 µM, 5-h incubation), we provided an important data associated with the role of mitochondrial-ROS production in the [Zn2+]i-dyshomeostasis of the ventricular cardiomyocytes from 24-month old rats. Overall, our present data, for the first time, demonstrated that a direct mitochondria-targeting antioxidant treatment can be a new therapeutic strategy during aging in the heart through a well-controlled [Zn2+] distribution among cytosol and suborganelles with altered expression levels of the Zn2+-transporters.

The transient cortical zone in the adrenal gland: the mystery of the adrenal X-zone

The X-zone is a transient cortical region enriched in eosinophilic cells located in the cortical–medullary boundary of the mouse adrenal gland. Similar to the X-zone, the fetal zone in human adrenals is also a transient cortical compartment, comprising the majority of the human fetal adrenal gland. During adrenal development, fetal cortical cells are gradually replaced by newly formed adult cortical cells that develop into outer definitive zones. In mice, the regression of this fetal cell population is sexually dimorphic. Many mouse models with mutations associated with endocrine factors have been reported with X-zone phenotypes. Increasing findings indicate that the cell fate of this aged cell population of the adrenal cortex can be manipulated by many hormonal and nonhormonal factors. This review summarizes the current knowledge of this transient adrenocortical zone with an emphasis on genes and signaling pathways that affect X-zone cells.