Aging-induced Changes Research Articles

Aging and Immunity in COVID-19

The COVID-18 pandemic severely affected people older than 65 years, especially those with age-related comorbidities, causing a disproportionate death burden in this age group. The reasons for this difference from other respiratory virus pandemics have been attributed to the aging-induced changes in the immune system, and their effects on the pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia. In this brief review, I summarize some of the recent findings throwing light on the relationship between aging, immunity, and the severity of COVID-19.

Impact of Exercise and Aging on Mitochondrial Homeostasis in Skeletal Muscle: Roles of ROS and Epigenetics.

Aging causes degenerative changes such as epigenetic changes and mitochondrial dysfunction in skeletal muscle. Exercise can upregulate muscle mitochondrial homeostasis and enhance antioxidant capacity and represents an effective treatment to prevent muscle aging. Epigenetic changes such as DNA methylation, histone posttranslational modifications, and microRNA expression are involved in the regulation of exercise-induced adaptive changes in muscle mitochondria. Reactive oxygen species (ROS) play an important role in signaling molecules in exercise-induced muscle mitochondrial health benefits, and strong evidence emphasizes that exercise-induced ROS can regulate gene expression via epigenetic mechanisms. The majority of mitochondrial proteins are imported into mitochondria from the cytosol, so mitochondrial homeostasis is regulated by nuclear epigenetic mechanisms. Exercise can reverse aging-induced changes in myokine expression by modulating epigenetic mechanisms. In this review, we provide an overview of the role of exercise-generated ROS in the regulation of mitochondrial homeostasis mediated by epigenetic mechanisms. In addition, the potential epigenetic mechanisms involved in exercise-induced myokine expression are reviewed.

Sex differences in vascular aging and impact of GPER deletion.

Aging is a nonmodifiable risk factor for cardiovascular disease associated with arterial stiffening and endothelial dysfunction. We hypothesized that sex differences exist in vascular aging processes and would be attenuated by global deletion of the G protein-coupled estrogen receptor. Blood pressure was measured by tail-cuff plethysmography, pulse wave velocity (PWV) and echocardiography were assessed with high-resolution ultrasound, and small vessel reactivity was measured using wire myography in adult (25 wk) and middle-aged (57 wk) male and female mice. Adult female mice displayed lower blood pressure and PWV, but this sex difference was absent in middle-aged mice. Aging significantly increased PWV but not blood pressure in both sexes. Adult female carotids were more distensible than males, but this sex difference was lost during aging. Acetylcholine-induced relaxation was greater in female than male mice at both ages, and only males showed aging-induced changes in cardiac hypertrophy and function. GPER deletion removed the sex difference in PWV and ex vivo stiffness in adult mice. The sex difference in blood pressure was absent in KO mice and was associated with endothelial dysfunction in females. These findings indicate that the impact of aging on arterial stiffening and endothelial function is not the same in male and female mice. Moreover, nongenomic estrogen signaling through GPER impacted vascular phenotype differently in male and female mice. Delineating sex differences in vascular changes during healthy aging is an important first step in improving early detection and sex-specific treatments in our aging population.NEW & NOTEWORTHY Indices of vascular aging were different in male and female mice. Sex differences in pulse wave velocity, blood pressure, and large artery stiffness were abrogated in middle-aged mice, but the female advantage in resistance artery vasodilator function was maintained. GPER deletion abrogated these sex differences and significantly reduced endothelial function in adult female mice. Additional studies are needed to characterize sex differences in vascular aging to personalize early detection and treatment for vascular diseases.

The Role of Comorbidities on Aging-Induced Changes in Muscle Health and Amino Acid Kinetics

ObjectivesAging and comorbidities are known to influence amino acid metabolism, contributing to reduced muscle and cognitive dysfunction in older adults. Whether these aging-induced manifestations remain after correction for the presence of comorbidities is unclear. MethodsOlder adults were selected from the MEDIT database. The subjects were divided into two age groups: 264 young old (age 50–70 y: n = 149 with at least 1 comorbidity based on Charlson comorbidity index (CCI > 0) and n = 115 with CCI = 0), and 196 middle old (age 70–85 y: n = 119 with CCI > 0 and n = 77 with CCI = 0). Body composition was assessed by DXA, respiratory and skeletal muscle strength by mouth pressures and dynamometry, and cognition and mood by assessments and questionnaires. Postabsorptive kinetics of multiple amino acids were measured by pulse stable isotope administration and subsequent blood sampling. Plasma amino acid concentrations and enrichments were analyzed by LC-MS/MS to measure whole-body protein production (WBP) and conversion rates. Statistics are done with ANCOVA with sex and BMI and age group as independents. Results expressed as means [95% CI]. ResultsThe middle old had lower lean mass on whole body level and in the extremities (p < 0.0001), and lower respiratory (p = 0.05) and handgrip (p = 0.005) strength compared to the young old, independent of muscle health lowering effects of CCI. Although no differences were observed in cognition and mood between the groups, an age x CCI interaction was found for depression, anxiety (p = 0.03), and lean mass extremity (p = 0.04). The middle old had lower values for WBP of tau-methylhistidine (p = 0.01), hydroxyproline (P = 0.008), and taurine (p = 0.004), and plasma glutamine concentration (P = 0.016). In addition, the middle old showed higher glutamine to glutamate conversion (p = 0.02). Age x CCI interaction was observed for plasma concentration of tyrosine (p = 0.04). No differences were observed in plasma concentrations and WBP of phenylalanine and the branched-chain amino acids (leucine, valine, and isoleucine) between the groups. ConclusionsMuscle loss and weakness and specific disturbances in amino acid kinetics due to aging exist even after correction for the presence of comorbidities. Funding SourcesNone

Determination of degradation modes of lithium-ion batteries considering aging-induced changes in the half-cell open-circuit potential curve of silicon–graphite

The shape of the open-circuit potential (OCP) curve of silicon–graphite blend electrodes changes during cycle aging due to the faster degradation of the silicon in comparison to the graphite. In this study, the impact of these changes on the open-circuit voltage (OCV) curve of full-cells is investigated. Reconstructing the OCV curve of aged cells by shifting and linearly scaling pristine half-cell OCP curves is an established diagnostic method of determining the degradation modes occurring in lithium-ion cells. We reconstruct the full-cell OCV curves of cycle-aged commercial cells with silicon–graphite anodes using both pristine and aged silicon–graphite OCP curves. Lower estimates are obtained for the loss of anode active material and higher estimates for the loss of both cathode active material and lithium inventory, when aging-induced changes in the shape of the silicon–graphite OCP are considered. Aging-induced changes in the shape of silicon–graphite OCP curves are integrated in the diagnostic method by using a blend electrode OCP model. This not only improves the validity of the determined degradation modes, but also enables the non-destructive estimation of the anode capacity fraction provided by silicon, based on full-cell OCV measurements.

Microbiota-microglia connections in age-related cognition decline.

Aging is an inevitable process that all individuals experience, of which the extent differs among individuals. It has been recognized as the risk factor of neurodegenerative diseases by affecting gut microbiota compositions, microglia, and cognition abilities. Aging‐induced changes in gut microbiota compositions have a critical role in orchestrating the morphology and functions of microglia through the gut‐brain axis. Gut microbiota communicates with microglia by its secreted metabolites and neurotransmitters. This is highly associated with age‐related cognitive declines. Here, we review the main composition of microbiota in the aged individuals, outline the changes of the brain in age‐related cognitive decline from a neuroinflammation perspective, especially the changes of morphology and functions of microglia, discuss the crosstalk between microbiota and microglia in the aged brain and further highlight the role of microbiota‐microglia connections in neurodegenerative diseases (Alzheimer's disease and Parkinson's disease).

Pentacyclic triterpene oleanolic acid protects against cardiac aging through regulation of mitophagy and mitochondrial integrity

Advanced aging exhibits altered cardiac geometry and function involving mitochondrial anomaly. Natural compounds display promises in the regulation of cardiac homeostasis via governance of mitochondrial integrity in aging. This study examined the effect of oleanolic acid (OA), a natural pentacyclic triterpenoid with free radical scavenging and P450 cyclooxygenase-regulating properties, on cardiac aging and mechanisms involved with a focus on mitophagy. Young (4–5 month-old) and old (22–24 month-old) mice were treated with OA for 6 weeks prior to assessment of cardiac function, morphology, ultrastructure, mitochondrial integrity, cell death and autophagy. Our data revealed that OA treatment alleviated aging-induced changes in myocardial remodeling (increased heart weight, chamber size, cardiomyocyte area and interstitial fibrosis), contractile function and intracellular Ca2+ handling, apoptosis, necroptosis, inflammation, autophagy and mitophagy (LC3B, p62, TOM20 and FUNDC1 but not BNIP3 and Parkin). OA treatment rescued aging-induced anomalies in mitochondrial ultrastructure (loss of myofilament alignment, swollen mitochondria, increased circularity), mitochondrial biogenesis and O2− production without any notable effect at young age. Interestingly, OA-offered benefit against cardiomyocyte aging was nullified by deletion of the mitophagy receptor FUNDC1 using FUNDC1 knockout mice, denoting an obligatory role for FUNDC1 in OA-elicited preservation of mitophagy. OA reconciled aging-induced changes in E3 ligase MARCH5 but not FBXL2, and failed to affect aging-induced rises in IP3R3. Taken together, our data indicated a beneficial role for OA in attenuating cardiac remodeling and contractile dysfunction in aging through a FUNDC1-mediated mechanism.

Effect of aging on shear strength of compacted GMZ bentonite

The shear strength characteristics of compacted bentonite preferred as feasible buffer/backfill component is essential to the mechanical stability of the multi-barrier system in the context of nuclear waste disposal. This paper presents an investigation on the potential aging-induced changes in shear strength and microstructure of compacted GMZ bentonite at a dry density of 1.68 Mg/m3 and various water contents. For this purpose, direct shear and Mercury Intrusion Porosimetry (MIP) tests were correspondingly performed, as well as the soil-water retention tests. Statically compacted bentonite specimens were kept at constant volume and water content conditions for different periods of aging time up to 90 days, prior to experimental investigations. Results showed that the shear strength decreased with aging time, with a more noticeable trend during the first 30 days. Aging effect on shear strength was less pronounced for specimens at water content of 24%. Significant changes in microstructure after aging were observed, characterized by an increase in tiny pores (< 6 nm) and a decrease in inter-aggregate pores. The former phenomenon is related to the interlayer hydration as water redistribution is expected to occur, while the latter one is attributed to the exfoliation of clay particles that fill and reduce the inter-aggregate pores, which accounts for the dry density effect on soil-water retention curves (SWRC). Aging-induced changes in microstructure are governed by the water uptake from the non-interlayer space acting as reservoir into the interlayer pores, thereby promoting a further clay layer hydration and an arrangement of clay fabric. As such, both the effective degree of saturation (mainly considering the capillary water) and total suction decreased with aging, as well as the Bishop-type effective stress, thereby resulting in a decrease in the shear strength of compacted GMZ bentonite.

Co-sorption/co-desorption mechanism of the mixed chlorobenzenes by fresh bulk and aged residual biochar

Since little is known about the sorption/desorption behaviors of the mixed chlorobenzenes (CBs) on fresh and aged biochar, this study evaluated the co-sorption/co-desorption mechanism of the mixed monochlorobenzene (MCB), 1,2-dichlorobenzene (1,2-DCB) and 1,2,4-tirchlorobenzene (1,2,4-TCB) on the fresh bulk biochar derived from pinewood sawdust and corn straw under the heat treatment temperature (HTT) of 300 and 500 °C, and elucidated the aging-induced changes in the sorption/desorption of mixed CBs by biochar. The distinct sorption capacities of MCB< 1,2-DCB< 1,2,4-TCB were observed on all the tested biochar with the differences being further enhanced following the rise of HTT, as the main sorption mechanism was converted from phase partitioning to π-π interaction between graphitized biochar moieties and more hydrophobic aromatic chemicals. In comparison to the fresh biochar, the sorption suppression of the mixed CBs on the aged biochar was likely attributable to the reduction in accessibility to the aromatic carbon in biochar by introducing O-containing polar moieties on the biochar surfaces. Intriguingly, the kinetics of desorption was decreased with the aging of biochar may be caused by the increase in surface steric hindrance. These findings can provide new insights on understanding the co-sorption/co-desorption mechanism of the mixed CBs and help assess and manage the application of biochar on the treatment of contaminated soil and groundwater under field conditions.

Aging-induced changes in mRNA expression of dopaminergic neuron-related genes in C57BL/6 mouse brain

Aging-induced changes in mRNA expression of dopaminergic neuron-related genes in C57BL/6 mouse brain

Determination of Degradation Modes of Lithium-Ion Batteries Considering Aging-Induced Changes in the Half-Cell Open-Circuit Potential Curve of Silicon-Graphite

Determination of Degradation Modes of Lithium-Ion Batteries Considering Aging-Induced Changes in the Half-Cell Open-Circuit Potential Curve of Silicon-Graphite

Assessment of physical function, quality of life, and medication adherence in elderly patients with rheumatic diseases

BackgroundThe proportion of older people in the total population has increased in Turkey as well as worldwide. As life expectancy rises, the increasing prevalence of rheumatic diseases poses major problems in the elderly. Comorbid diseases and the aging-induced changes in the endogenous immune response and the pharmacokinetic properties of therapeutic agents may complicate the decision to use a particular drug and result in a different clinical picture and treatment response. We, therefore, aimed to investigate the characteristics of chronic inflammatory diseases, their impact on physical function and quality of life, the prevalence of comorbid diseases that may complicate treatment planning, and treatment adherence in patients aged 65 years or older.ResultsOne hundred seventy-four patients were included and divided into two age groups: 18–64 years (group 1, n = 85) and 65 years or older (group 2, n = 89). The mean age of all recruited patients was 57.55 ± 16.98 years. Of 174, 99 (56.9%) were female and 75 (43.1%) were male. The mean duration of rheumatic disease was 7 ± 4.8 years and age at onset was 51.46 ± 14.78 years. Gender distribution differed significantly by age group (P = 0.024). The percentage of females in group 1 was 48.2% and 65.2% in group 2. The occupational status also differed significantly by age group (P < 0.001). 48.2% of group 1 were employed and 57.3% of group 2 were housewives. Marital status varied significantly by age (P < 0.001). The percentage of married was 74.1% in group 1 and the percentage of separated/divorced/widowed in group 2 was 28.1%. There was no difference between groups 1 and 2 in terms of place of residence (P = 0.459). The prevalence of comorbid diseases and the rate of use of medications for comorbid diseases (non-rheumatic treatments) were higher in elderly patients. The rate of use of disease-modifying anti-rheumatic drugs (DMARDs) was 30.3% and biological agents 61.8% in the elderly group (≥ 65 years) (group 2) (P < 0.001). There were positive correlations between, Health Assessment Questionnaire (HAQ), Bath Ankylosing Spondylitis Functional Index (BASFI) and Nottingham Health Profile (NHP) domains in both groups. There was also a significant negative correlation between Medication Adherence Rating Scale (MARS) and all dimensions.ConclusionsElderly and younger patients with rheumatic diseases have different demographic and clinical characteristics. Physical function and quality of life are more affected by rheumatic diseases and treatment adherence is poorer in the elderly. Our study found a positive correlation between physical function and quality of life in both age groups. The treatment adherence rating scale showed a negative correlation with physical function and quality of life scores, with individuals with poor treatment adherence having worse physical function and quality of life.

Abstract 9051: Gender Differences and Aging on Beta-Adrenergic Receptor Subtypes Expression and Function in Murine Left Ventricular Myocytes

Background: Sex-specific modulation of β-adrenergic receptor (AR) stimulation plays a pivotal role in cardiac function and in the manifestation of heart disease, including aging. However, the sex and age influences on 3 cardiac β-AR subtypes have not been systematically evaluated. Their effects on β 1 -AR have yielded mixed results. Virtually no previous studies have examined sex and age-related changes on the functional cardiac β 3 -AR. We hypothesized that sex differences exist in aging-induced changes in myocyte β 1 - and β 3 -AR. Aged males may exhibit a greater selective β 1 -AR downregulation with a more pronounced decline of β-AR reserve. Methods: LV myocytes were obtained from young (Y) (6 mo) and aged (A) (24 mo) (6/group) male (M) and female (F) wild-type mice. We simultaneously compared LV myocyte protein levels of β 1 -, β 2 -, and β 3 -AR, and the responses of cell contractile function (dL/dt max ) to β-AR subtype stimulation by random exposure of myocytes to isoproterenol (ISO) (10 -8 M) or a selective β 1 -, β 2 -, or β 3 -agonist, Norepinephrine (NE, 10 -7 M), Zinterol (ZIN,10 -5 M) and BRL-37,344 (BRL,10 -8 M), respectively. Results: In Y mice, no sex differences were found in myocyte protein levels of β 1 - (YM: 0.73 vs YF: 0.74), β 2 - (0.28 vs 0.29) and β 3 -AR (0.19 vs 0.17). Consistently, there were similarly significant increases in dL/dt max in responses to ISO (YM: 73%, 209.5 vs121.1; YF: 72%, 210.7 vs122.5 μm/s), NE (48% vs 45%), ZIN (18% vs 20%) and decrease after BRL (8.1% vs 7.9%). Compared with sex-matched Y, in both AM and AF, aging caused a ~58% significant increase in β 3 (AM: 0.30 vs AF: 0.27) and slightly reduced β 2 (11% vs 6%) (P=NS). Aging caused ~30% decline in basal cell contractility. No sex differences in dL/dt max of aging myocyte response to ZIN (increased AM: 17% vs AF: 20%), and BRL (decreased 19% vs 21%). However, in AM, β 1 decreased 33% (0.48) which was significantly greater than that in AF (26%, 0.55). Versus AF, in AM, ISO caused significantly less increase in dL/dt max (34% vs 48%) accompanied by attenuated NE-mediated increase in dL/dt max (17% vs 26%). Conclusions: Aging is associated with LV myocyte β 1 -AR downregulation and β 3 -AR upregulation. Sex affects age-related β 1 -AR downregulation, with males exhibiting a more profound decrease with increasing age.

Ageing reduces skin wetness sensitivity across the body.

What is the central question of this study? Ageing impairs the skin's thermal and tactile sensitivity: does ageing also induce loss of skin wetness sensitivity? What is the main finding and its importance? Older adults show an average 15% loss of skin wetness sensitivity, with this sensory deficit being mediated by a combination of reductions in skin's tactile sensing and hydration status. These findings increase knowledge of wetness sensing mechanisms across the lifespan. Humans use sensory integration mechanisms to sense skin wetness based on thermal and mechanical cues. Ageing impairs the skin's thermal and tactile sensitivity, yet we lack evidence on whether wetness sensing also changes with ageing. We mapped local skin wetness and temperature sensitivity in response to cold-, neutral- and warm-wet stimuli applied to the forehead, neck, lower back, dorsal foot, index finger and thumb, in 10 Younger (22.4±1.1years) and 10 Older (58.2±5.1years) males. We measured local skin temperature and conductance (i.e., a marker of hydration status) at the tested sites, to establish the role of skin's thermal and mechanical parameters in ageing-induced changes in wetness sensing. Irrespective of body site, Older reported overall lower wetness perceptions than Younger across all wet-stimulus temperatures (mean difference: -14.6mm; 95% CI: -4.3, -24.9; P=0.008; ∼15% difference). When considering regional wetness sensitivity, the effect of ageing was more pronounced in response to the cold-wet stimulus over the lover back (mean difference Older vs. Younger: -36.8mm; 95% CI: -68.4, -5.2; P=0.014; ∼37% difference) and dorsal foot (mean difference: -37.1mm; 95% CI: -68.7, -5.5; P=0.013; ∼37% difference). We found no differences between age groups on overall thermal sensations (P=0.744) nor local skin temperature (P=0.372); however, we found that Older presented overall lower skin conductance than Younger (mean difference: -1.56μS; 95% CI: -0.49, -2.62; P=0.005), which corresponded to an ∼78% reduction in skin hydration. We conclude that skin wetness sensing decreases with ageing primarily due to age-induced changes in skin mechanics and tactile sensitivity.

Aging weakens Th17 cell pathogenicity and ameliorates experimental autoimmune uveitis in mice

Aging-induced changes in the immune system are associated with a higher incidence of infection and vaccination failure. Lymph nodes, which filter the lymph to identify and fight infections, play a central role in this process. However, careful characterization of the impact of aging on lymph nodes and associated autoimmune diseases is lacking. We combined single-cell RNA sequencing (scRNA-seq) with flow cytometry to delineate the immune cell atlas of cervical draining lymph nodes (CDLNs) of both young and old mice with or without experimental autoimmune uveitis (EAU). We found extensive and complicated changes in the cellular constituents of CDLNs during aging. When confronted with autoimmune challenges, old mice developed milder EAU compared to young mice. Within this EAU process, we highlighted that the pathogenicity of T helper 17 cells (Th17) was dampened, as shown by reduced GM-CSF secretion in old mice. The mitigated secretion of GM-CSF contributed to alleviation of IL-23 secretion by antigen-presenting cells (APCs) and may, in turn, weaken APCs’ effects on facilitating the pathogenicity of Th17 cells. Meanwhile, our study further unveiled that aging downregulated GM-CSF secretion through reducing both the transcript and protein levels of IL-23R in Th17 cells from CDLNs. Overall, aging altered immune cell responses, especially through toning down Th17 cells, counteracting EAU challenge in old mice.

Hippocampal microglia are vulnerable to aging-induced pro-inflammatory morphological changes that are partly alleviated by M. vaccae immunization

Hippocampal microglia are vulnerable to aging-induced pro-inflammatory morphological changes that are partly alleviated by M. vaccae immunization

Sirtuin 3 (SIRT3) Pathways in Age-Related Cardiovascular and Neurodegenerative Diseases.

Age-associated cardiovascular and neurodegenerative diseases lead to high morbidity and mortality around the world. Sirtuins are vital enzymes for metabolic adaptation and provide protective effects against a wide spectrum of pathologies. Among sirtuins, mitochondrial sirtuin 3 (SIRT3) is an essential player in preserving the habitual metabolic profile. SIRT3 activity declines as a result of aging-induced changes in cellular metabolism, leading to increased susceptibility to endothelial dysfunction, hypertension, heart failure and neurodegenerative diseases. Stimulating SIRT3 activity via lifestyle, pharmacological or genetic interventions could protect against a plethora of pathologies and could improve health and lifespan. Thus, understanding how SIRT3 operates and how its protective effects could be amplified, will aid in treating age-associated diseases and ultimately, in enhancing the quality of life in elders.

Non-Destructive Degradation Diagnostics of Lithium-Ion Cells Considering Aging-Related Changes in the Shape of the Half-Cell Open Circuit Potential Curve of Silicon-Graphite

Analyzing changes in the quasi-stationary open circuit potential (OCP) curve during aging is a well-established method for the non-destructive diagnosis of degradation occurring in lithium-ion cells during calendar and cycle aging. It allows detecting and quantifying different degradation modes, especially loss of lithium inventory and loss of active material at a specific electrode, without the need of opening up the cells and performing post-mortem analysis. In order to obtain information on the degradation, the quasi-stationary OCP curve measured from an aged cell is reconstructed based on the half-cell OCP curves of the electrode materials. For this purpose, both half-cell OCP curves are linearly scaled and relatively shifted against each other until the difference between cathode and anode OCP fits the measured full-cell OCP. The parameters for the scaling and shifting of the half-cell OCP curves obtained during this optimization procedure are quantitative indicators of the degradation modes that have occurred in the full-cell. Usually, half-cell OCP curves obtained from pristine electrode material are used in this process and the shape of the half-cell OCP curves is assumed invariant during aging.While this assumption is probably justified for graphite and most established cathode materials, there are a number of recent publications describing a change in the shape of the OCP curve of blended silicon-graphite electrodes during cycle aging. This change is probably mainly caused by a decrease in the relative contribution of the silicon to the overall electrode capacity because of its faster degradation in comparison with the graphite. In this study, we investigate the influence of aging-induced changes in the shape of the OCP of silicon-graphite on the applicability of the method for non-destructive degradation analysis described above for cells containing silicon-graphite as anode material. We also present possible extensions of this method to consider changes on the half-cell level.In the scope of this study, we cycle commercial lithium-ion cells containing nickel-rich nickel manganese cobalt oxide (NMC-811) as cathode material and silicon-graphite as anode material until different degradation stages are reached. We then measure the quasi-stationary OCP of the full-cell and subsequently open the cells to extract samples from both electrodes. Afterwards, we measure the quasi-stationary OCP curve of the electrode samples by building coin-cells containing an electrode sample as cathode and lithium metal as anode.We reconstruct the full-cell OCP curves at different degradation stages by linear scaling and shifting of half-cell OCP curves both obtained from pristine electrodes and from the electrodes extracted from aged cells as shown in figure 1. This allows us to analyze whether the accuracy of the full-cell OCP reconstruction can be improved by using half-cell OCP curves of aged electrodes. We also present the changes in the quantitative results concerning the occurrence of different aging modes depending on whether pristine or aged half-cell OCP curves are used to reconstruct the full-cell OCP.In addition to this, we present an extended method for non-destructive degradation diagnostics that contains silicon-specific active material degradation as an additional aging mode. We analyze to which degree this method is capable of determining the loss of silicon-related capacity in the anode from full-cell OCP measurements.These results are relevant for both science and application as lithium-ion cells containing blended silicon-graphite as anode material are increasingly used due to their high specific capacity. Adapting the methods for aging diagnosis to this anode material is necessary to obtain valid results from experiments investigating the degradation of full-cells containing silicon-graphite anodes. Furthermore, expanding the existing models describing the aging-related change in full-cell OCP curves by considering changes in the shape of the half-cell OCP curves is a first step for the development of reliable algorithms for electrode-specific state of health estimation for cells containing silicon-graphite. Such algorithms could then be used on-board as part of the functionality of battery management systems.Figure 1: Reconstruction of the open circuit potential curve of a cycle aged full-cell based on both half-cell open circuit potential curves obtained from pristine and cycle aged electrodes Figure 1

Young Plasma Induces Antidepressant-Like Effects in Aged Rats Subjected to Chronic Mild Stress by Suppressing Indoleamine 2,3-Dioxygenase Enzyme and Kynurenine Pathway in the Prefrontal Cortex.

Pathophysiology of depression in elderlies is linked to aging-associated increase in indoleamine 2,3-dioxygenase (IDO) levels and activity and kynurenine (Kyn) metabolites. Moreover, these aging-induced changes may alter the brain's responses to stress. Growing evidence suggested that young plasma can positively affect brain dysfunctions in old age. The present study aimed to investigate whether the antidepressant effects of young plasma administration in aged rats subjected to chronic unpredictable mild stress (CUMS) and underlying mechanisms, focusing on the prefrontal cortex (PFC). Young (3months old) and aged (22months old) male rats were divided into five groups; young control, aged control, aged rats subjected to CUMS (A + CUMS), aged rats subjected to CUMS and treated with young plasma (A + CUMS + YP), and aged rats subjected to CUMS and treated with old plasma (A + CUMS + OP). Plasma was injected (1ml, intravenously) three times per week for four weeks. Young plasma significantly improved CUMS-induced depressive-like behaviors, evidenced by the increased sucrose consumption ratio in the sucrose preference test and the reduced immobility time in the forced swimming test. Furthermore, young plasma markedly reduced the levels of interferon-gamma (IFN-γ), IDO, Kyn, and Kyn to tryptophan (Kyn/Trp) ratio in PFC tissue. Expression levels of the serotonin transporter and growth-associated protein (GAP)-43 were also significantly increased after chronic administration of young plasma. These findings provide evidence for the antidepressant effect of young plasma in old age; however, whether it improves depressive behaviors or faster recovery from stress-induced deficits is required to be elucidated.

Endothelium-specific deletion of amyloid-β precursor protein exacerbates endothelial dysfunction induced by aging.

The physiological function of amyloid precursor protein (APP) in the control of endothelial function during aging is unclear. Aortas of young (4-6 months old) and aged (23-26 months old) wild-type (WT) and endothelium-specific APP-deficient (eAPP−/−) mice were used to study aging-induced changes in vascular phenotype. Unexpectedly, aging significantly increased protein expression of APP in aortas of WT mice but not in aortas of eAPP−/− mice thereby demonstrating selective upregulation APP expression in vascular endothelium of aged aortas. Most notably, endothelial dysfunction (impairment of endothelium-dependent relaxations) induced by aging was significantly exacerbated in aged eAPP−/− mice aortas as compared to age-matched WT mice. Consistent with this observations, endothelial nitric oxide synthase (eNOS) protein expression was significantly decreased in aged eAPP−/− mice as compared to age matched WT mice. In addition, protein expression of cyclooxygenase 2 and release of prostaglandins were significantly increased in both aged WT and eAPP−/− mice. Notably, treatment with cyclooxygenase inhibitor, indomethacin, normalized endothelium-dependent relaxations in aged WT mice, but not in aged eAPP−/− mice. In aggregate, our findings support the concept that aging-induced upregulation of APP in vascular endothelium is an adaptive response designed to protect and preserve expression and function of eNOS.