Patient-Reported Outcomes of Accelerated Aging: A Novel Approach to Investigate Second Cancer Risk in Adolescent and Young Adult (18-39 Years) Cancer Survivors.

BACKGROUND: Adolescent and young adult cancer survivors (AYAs, aged 18-39 years at first diagnosis) have a higher second cancer risk. Accelerated aging is hypothesized as underlying mechanism and has been described clinically by 6 indicators; fatigue, low quality of sleep, low mood, lack of motivation, subjective memory complaints, and poor exercise tolerance. Using patient-reported outcomes, we aimed to identify clusters of accelerated aging among AYA cancer survivors and to investigate their association with second cancer development. PATIENTS AND METHODS: Patient, tumor, and treatment data were obtained from the Netherlands Cancer Registry. Patient-reported clinical indicators and second cancer data were obtained from the SURVivors (5-20 years) of cancer in AYAs (SURVAYA) questionnaire study between 1999 and 2015. Latent class and multivariable logistic regression analyses were performed. RESULTS: In total, n = 3734 AYA survivors with known second cancer status (n = 278 [7.4%] second cancers) were included. Four latent clusters were identified and named based on their clinical indicator features; (1) high accelerated aging (31.3%), (2) intermediate accelerated aging without poor exercise tolerance (15.1%), (3) intermediate accelerated aging without lack of motivation (27.4%), and (4) low accelerated aging (26.2%). AYAs in the high accelerated aging cluster were more likely to have second cancer (odds ratio: 1.6; 95% CI, 1.1-2.3) compared to the low accelerated aging cluster. CONCLUSION: AYAs with a higher burden of accelerated aging were more likely to develop a second cancer. Validation of the clinical indicators and how to best capture them is needed to improve (early) detection of AYAs at high risk of developing second cancer.

Endothelial deficiency of insulin-like growth factor-1 receptor leads to blood-brain barrier disruption and accelerated endothelial senescence in mice, mimicking aspects of the brain aging phenotype.

INTRODUCTION: Age-related blood-brain barrier (BBB) disruption, cerebromicrovascular senescence, and microvascular rarefaction substantially contribute to the pathogenesis of vascular cognitive impairment (VCI) and Alzheimer's disease (AD). Previous studies established a causal link between age-related decline in circulating levels of insulin-like growth factor-1 (IGF-1), cerebromicrovascular dysfunction, and cognitive decline. The aim of our study was to determine the effect of IGF-1 signaling on senescence, BBB permeability, and vascular density in middle-age and old brains. METHODS: Accelerated endothelial senescence was assessed in senescence reporter mice (VE-Cadherin-CreERT2 /Igf1rfl/fl × p16-3MR) using flow cytometry. To determine the functional consequences of impaired IGF-1 input to cerebromicrovascular endothelial cells, BBB integrity and capillary density were studied in mice with endothelium-specific knockout of IGF1R (VE-Cadherin-CreERT2 /Igf1rfl/fl ) using intravital two-photon microscopy. RESULTS: In VE-Cadherin-CreERT2 /Igf1rfl/fl mice: (1) there was an increased presence of senescent endothelial cells; (2) cumulative permeability of the microvessels to fluorescent tracers of different molecular weights (0.3-40 kDa) is significantly increased, as compared to that of control mice, whereas decline in cortical capillary density does not reach statistical significance. CONCLUSIONS: These findings support the notion that IGF-1 signaling plays a crucial role in preserving a youthful cerebromicrovascular endothelial phenotype and maintaining the integrity of the BBB.

Longitudinal study of traumatic-stress related cellular and cognitive aging.

Traumatic stress is associated with both accelerated epigenetic age and increased risk for dementia. Accelerated epigenetic age might link symptoms of traumatic stress to dementia-associated biomarkers, such as amyloid-beta (Aß) proteins, neurofilament light (NFL), and inflammatory molecules. We tested this hypothesis using longitudinal data obtained from 214 trauma-exposed military veterans (85 % male, mean age at baseline: 53 years, 75 % White) who were assessed twice over the course of an average of 5.6 years. Cross-lagged panel mediation models evaluated measures of lifetime posttraumatic stress disorder and internalizing and externalizing comorbidity (assessed at Time 1; T1) in association with T1 epigenetic age (per the GrimAge algorithm) and T1 plasma markers of neuropathology along with bidirectional temporal paths between T1 and T2 epigenetic age and the plasma markers. Results revealed that a measure of externalizing comorbidity was associated with accelerated epigenetic age (ß = 0.30, p <.01), which in turn, was associated with subsequent increases in Aß-40 (ß = 0.20, p <.001), Aß-42 (ß = 0.18, p <.001), and interleukin-6 (ß = 0.18, p <.01). T1 advanced epigenetic age and the T1 neuropathology biomarkers NFL and glial fibrillary acidic protein predicted worse performance on T2 neurocognitive tasks assessing working memory, executive/attentional control, and/or verbal memory (ps = 0.03 to 0.009). Results suggest that advanced GrimAge is predictive of subsequent increases in neuropathology and inflammatory biomarkers as well as worse cognitive function, highlighting the clinical significance of this biomarker with respect to cognitive aging and brain health over time. The finding that advanced GrimAge mediated the association between psychiatric comorbidity and future neuropathology is important for understanding potential pathways to neurodegeneration and early identification of those at greatest risk.

Does BioAge identify accelerated aging in individuals with bipolar disorder? An exploratory study in the FACE-BD cohort.

BACKGROUND: Individuals with bipolar disorders (BD) have an estimated loss of life expectancy around 10-15 years. Several laboratory-measured biomarkers of accelerated aging exist (e.g., telomere length), however with a questionable transferability to bedside. There is a need for easily and inexpensively measurable markers of aging, usable in routine practice, such as BioAge. METHODS: We calculated BioAge that estimates biological age based on routine blood tests and a physical exam, in a sample of 2220 outpatients with BD. We investigated associations between BioAge Acceleration (BioAgeAccel), which is an indicator of accelerated aging, and sociodemographic variables, clinical variables, and current psychotropic medication use. RESULTS: Mean chronological age was 40.2 (±12.9). Mean BioAge was 39.1 (±12.4). Mean BioAgeAccel was 0.08 (±1.8). A minority of individuals (15%) had a BioAgeAccel above 2 years. Multivariable analyses suggested strong associations between a higher BioAgeAccel and younger age, male sex, overweight and sleep disturbances. Regarding current psychotropic medication use, discrepancies between univariate and multivariate analyses were observed. CONCLUSIONS: A minority of individuals with BD had an accelerated aging as measured by BioAge. We identified associations with potentially modifiable factors, such as higher body mass index and sleep disturbances, that are however nonspecific to BD. These results require replications in independent samples of individuals with BD, and comparisons with a control group matched for age and gender. Longitudinal studies are also required to test whether any change in metabolic health, or sleep might decrease BioAgeAccel.

Accelerated aging behavior of degradable and non-degradable microplastics via advanced oxidation and their adsorption characteristics towards tetracycline.

The increasing global utilization of biodegradable plastics due to stringent regulations on traditional plastics has caused a significant rise in microplastic (MPs) pollution in aquatic ecosystems from biodegradable products. However, the environmental behavior of biodegradable MPs remains inadequately elucidated. This study explored the aging processes of polylactic acid (PLA) and polystyrene (PS) under a heat-activated potassium persulfate (K2S2O8) system, as well as their adsorption characteristics towards tetracycline (TCs). In comparison to PS, the surface structure of PLA experienced more pronounced changes over aging, exhibiting evident pits, cracks, and fragmentation. The carbonyl index (CI) and oxygen/carbon ratio (O/C) of PS displayed exponential growth over time, whereas the values for PLA showed linear and exponential increases, respectively. The adsorption capacity of TCs by PS and PLA aged for 6 days increased from 0.312 mg‧g-1 and 0.457 mg‧g-1for original PS and PLA, respectively, to 0.372 mg‧g-1 and 0.649 mg‧g-1. Meanwhile, the adsorption rate (k2 values) for TCs decreased by 42.03 % for PS and 79.64 % for PLA compared to their initial values. The findings indicated that biodegradable PLA-MPs may exhibit higher tetracycline carrying capacities than PS, potentially increasing environmental and organismal risks, particularly in view of aging effects.

Stability Study of Synthetic Diamond Using a Thermally Controlled Biological Environment: Application towards Long-Lasting Neural Prostheses.

This paper demonstrates, for the first time, the stability of synthetic diamond as a passive layer within neural implants. Leveraging the exceptional biocompatibility of intrinsic nanocrystalline diamond, a comprehensive review of material aging analysis in the context of in-vivo implants is provided. This work is based on electric impedance monitoring through the formulation of an analytical model that scrutinizes essential parameters such as the deposited metal resistivity, insulation between conductors, changes in electrode geometry, and leakage currents. The evolution of these parameters takes place over an equivalent period of approximately 10 years. The analytical model, focusing on a fractional capacitor, provides nuanced insights into the surface conductivity variation. A comparative study is performed between a classical polymer material (SU8) and synthetic diamond. Samples subjected to dynamic impedance analysis reveal distinctive patterns over time, characterized by their physical degradation. The results highlight the very high stability of diamond, suggesting promise for the electrode's enduring viability. To support this analysis, microscopic and optical measurements conclude the paper and confirm the high stability of diamond and its strong potential as a material for neural implants with long-life use.

Sex as a Determinant of Age-Related Changes in the Brain.

The notion of notable anatomical, biochemical, and behavioral distinctions within male and female brains has been a contentious topic of interest within the scientific community over several decades. Advancements in neuroimaging and molecular biological techniques have increasingly elucidated common mechanisms characterizing brain aging while also revealing disparities between sexes in these processes. Variations in cognitive functions; susceptibility to and progression of neurodegenerative conditions, notably Alzheimer's and Parkinson's diseases; and notable disparities in life expectancy between sexes, underscore the significance of evaluating aging within the framework of gender differences. This comprehensive review surveys contemporary literature on the restructuring of brain structures and fundamental processes unfolding in the aging brain at cellular and molecular levels, with a focus on gender distinctions. Additionally, the review delves into age-related cognitive alterations, exploring factors influencing the acceleration or deceleration of aging, with particular attention to estrogen's hormonal support of the central nervous system.

Accelerated Aging in Cancer Survivors: Cellular Senescence, Frailty, and Possible Opportunities for Interventions.

The population of cancer survivors has markedly increased due to the rapid improvements in cancer treatment. However, cancer survivors experience accelerated aging, which leads to chronic diseases and other age-related conditions, such as frailty. Those conditions may persist years after cancer diagnosis and treatment. Cellular senescence, a hallmark of aging, is one of the mechanisms that contribute to accelerated aging in cancer survivors. Several aging measures, including measures based on clinical markers and biomarkers, have been proposed to estimate the aging process, and some of them have shown associations with mortality and frailty in cancer survivors. Several anti-aging interventions, including lifestyle changes and anti-aging drugs, have been proposed. Future research, particularly in large-scale studies, is needed to determine the efficiency of these aging measures and anti-aging interventions before considering their application in clinics. This review focuses on the mechanisms of cellular senescence and accelerated aging in cancer survivors, assessment of the aging process using clinical markers and biomarkers, and the high prevalence of frailty in that population, as well as possible opportunities for anti-aging interventions. A deeper understanding of aging measures and anti-aging interventions in cancer survivors will contribute to the development of effective strategies to mitigate accelerated aging in cancer survivors and improve their quality of life.

Chemical Structure and Thermal Properties versus Accelerated Aging of Bio-Based Poly(ether-urethanes) with Modified Hard Segments.

Aging of polymers is a natural process that occurs during their usage and storage. Predicting the lifetime of polymers is a crucial aspect that should be considered at the design stage. In this paper, a series of bio-based thermoplastic poly(ether-urethane) elastomers (bio-TPUs) with modified hard segments were synthesized and investigated to understand the structural and property changes triggered by accelerated aging. The bio-TPUs were synthesized at an equimolar ratio of reagents using the prepolymer method with the use of bio-based poly(trimethylene ether) glycol, bio-based 1,3-propanediol, and hexamethylene diisocyanate or hexamethylene diisocyanate/partially bio-based diisocyanate mixtures. The polymerization reaction was catalyzed by dibutyltin dilaurate (DBTDL). The structural and property changes after accelerated aging under thermal and hydrothermal conditions were determined using Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and dynamic mechanical thermal analysis (DMTA). Among other findings, it was observed that both the reference and aged bio-TPUs decomposed in two main stages and exhibited thermal stability up to approximately 300 °C. Based on the research conducted, it was found that accelerated aging impacts the supramolecular structure of TPUs.

[Demographic and professional risks of depopulation among working population in Russia: 14 years later (analytical review).]

The article presents a comparative analysis of the process of population aging in the context of demographic and professional risks of depopulation among working population in Russia. The values of the main medical and demographic indicators of population aging for Russia and developed countries were given. The results of UN forecasts, probabilistic forecasts of the total number and some characteristics of the age-sex structure for the population of the Russian Federation were analyzed. The state of demographic disadvantage in Russia and in the world was convincingly shown. Particular attention was paid to the consideration of the demographic risks of a reduction in the working-age population and an increase in the burden on the working-age population. The need for further research on the use of geroprotectors and modern gerontotechnologies as means and methods for preventing premature decline in work ability, slowing down the aging process of workers, reducing the mortality rate among working population and increasing professional longevity has been proven.

[Chronic kidney disease and accelerated aging: the role of comprehensive geriatric assessment.]

This review presents data from the literature on the characteristics of the course of chronic kidney disease from the perspective of the geriatric patient. Chronic kidney disease and progression of renal failure is a prototype model of premature and accelerated aging. Many authors have stated that a better mechanistic understanding of the phenomenon of premature aging, early diagnosis of chronic kidney disease, and a geriatric approach to the patient can improve the effectiveness of management and prolongation of life in this category of patients. Comprehensive geriatric assessment is one of the most important tools used by geriatricians and their teams to globally assess elderly patients and plan effective interventions. It is concluded that the use of comprehensive geriatric assessment in patients with chronic kidney disease may improve the clinical status of patients and allow selection of patients who may benefit most from renal replacement therapy compared to a conservative approach. And even in the early stages of chronic kidney disease, a comprehensive geriatric assessment may be useful in formulating a complete intervention plan and optimizing quality of life, autonomy, and prognosis. However, despite recognition of the importance of comprehensive geriatric assessment, the means to implement this tool in nephrology departments have not been developed and require special training programs and appropriate skills. It is concluded that much more needs to be done to realize the continuity of nephrologists and geriatricians in the provision of meaningful skilled care to older patients with chronic kidney disease.

The effect of aging on the translucency of contemporary zirconia generations: in-vitro study.

BACKGROUND: The translucency of different zirconia generations at each time point after thermocycling aging is still lacking. METHODS: Four zirconia materials were used with a total of 60 samples produced from monolithic third generation (5Y) 5 mol% yttria-stabilized zirconia polycrystalline ceramic and fourth generation zirconia (4Y) 4 mol% yttria-stabilized zirconia polycrystalline ceramic, represented by [group1:[CM-5Y] Ceramill Zolid fx (3rd generation zirconia) (Amann Girrbach, Koblach, Austria), group 2:[CM-4Y] Ceramill Zolid HT + (4th generation zirconia) (Amann Girrbach, Koblach, Austria), group 3:[CC-5Y] Cercon XT/ML (Dentsply Sirona, Germany) (3rd generation), and group 4:[CC-4Y] Cercon HT/ML (Dentsply Sirona, Germany) (4th generation)]. The L*a*b* figures were measured by using a spectrophotometer at baseline and after 10,000, 30,000, and 50,000 cycles of thermocycling. At each interval, the translucency of the samples was estimated by using the translucency formula CIEDE2000. The Scheffe post-hoc compared differences among each of the four materials. The Repeated measures ANOVA tested the differences between the materials at each of the different thermocycling intervals (p < .001). Data analyses were evaluated at a significance level of p < .05 (CI 95%). RESULTS: Two-way ANOVA revealed that at baseline the third and fourth generation's zirconia showed statistically significant differences in translucency (P < .001). Translucency values at baseline and after thermocycling exhibited statistically significant changes (p = .003). At each of the time interval; CM-4Y had the highest translucency values followed by CM-5Y, CC-4Y and CC-5Y had the least translucency values. CONCLUSIONS: The third and fourth generations of zirconia displayed different translucencies. Thermocycling affected the translucency of both third and fourth generations of zirconia. At each of the time intervals group 2:[CM-4Y] had the highest TP followed by group1:[CM-5Y], while, group 3:[CC-5Y] and group 4:[CC-4Y] had the least TP.

Color stability of dual-cured and light-cured resin cements: A systematic review and meta-analysis of in vitro studies.

PURPOSE: This systematic review and meta-analysis aimed to evaluate the difference in the color stability of light-cured and dual-cured resin cements. MATERIALS AND METHODS: Two separate reviewers used the PubMed, Scopus, Web of Science, Embase, and Scielo databases to execute the systematic review. For the analysis, studies that evaluated the color stability of dual-cured and light-cured resin cements over time were used. The random effects model was used in the meta-analysis. Analyses of subgroups were carried out based on the aging technique. The methodological quality of each in vitro study was evaluated in accordance with the parameters of a prior systematic review. RESULTS: From all databases, a total of 2223 articles were retrieved. Following the screening of titles and abstracts, 44 studies were selected for full text review, and a total of 27 articles were used for the qualitative analysis. Finally, 23 articles remained for the qualitative analysis. The majority of studies were labeled as having a medium risk of bias. The global analysis showed that the dual-cure resin cements had considerably greater differences in the color change (p = 0.006). A high heterogeneity index (86%) was found in the analysis. CONCLUSIONS: The best available in vitro evidence suggests that dual-polymerizing cement has higher color variation than light-polymerized materials. To reduce the likelihood of color change after the luting of thin ceramic restorations, clinicians should employ light-polymerizable resin cements.

Biocompatibility profile of aged pigmented and non-pigmented silicone elastomer for combined maxillofacial defects.

PURPOSE: To assess the biocompatibility of platinum silicone elastomer A-2000 used in combined maxillofacial defects prosthesis, after being deteriorated by an accelerated aging process resembling both the extra and intraoral environment. This assessment was done indirectly on human-derived dermal and gingival tissues. MATERIALS AND METHODS: One hundred eight samples of room-temperature vulcanized A-2000 platinum silicone were equally divided into extrinsically pigmented and non-pigmented groups to replicate combined maxillofacial defects. Accelerated aging was applied to pigmented samples to mimic extra- and intra-oral conditions, while non-aged counterparts served as controls. After isolating human cell lineages, dermal and gingival fibroblasts were indirectly exposed to silicone sample media. Cytotoxicity to cultured fibroblasts was assessed via MTT assay. Statistical significance was determined by repeated measures of one-way ANOVA (p < 0.01), evaluating cytotoxicity on dermal and gingival fibroblasts. RESULTS: MTT assay showed increased cytotoxicity in pigmented silicon samples subjected to extraoral aging compared to non-aged counterparts (p < 0.01). Non-pigmented silicon, modeling intraoral conditions, exhibited cytotoxicity after 48 h (p < 0.05). Both aged and non-aged silicon extracts equally sensitized gingival fibroblasts at 72 h (p < 0.001). Negative correlations between pigmented and non-pigmented silicon were observed in dermal cell growth (p > 0.05, except at 24 h, r = 0.2), with accelerated aging showing minimal impact on the pigmentation effect (p > 0.05). CONCLUSION: The retrieved diminished cellular metabolic activity of platinum silicone elastomer was in an acceptable clinical range, pointing out the importance of periodic assessments of the maxillofacial prosthesis for replacement depending on aging and cytotoxic harmful cellular responses.

Model of Accelerated Aging in CB6F2 Mice Induced by Ionizing Radiation.

A model for accelerated aging in mice was developed: CB6F2 mice aged 39-45 days were exposed to fractionated 4-fold relatively uniform γ-radiation (137Cs, 0.98 Gy/min) at a total dose of 6.8 Gy. Radiation exposure led to delayed active growth, leukopenia, and lymphopenia for over 1 year during the post-radiation period. The death of irradiated males and females occurred significantly earlier than in control group animals. Median lifespans in the experimental group were 35-38% lower than in the control group (p<0.001). Ionizing radiation exposure led to the early development of hair depigmentation, cachexia, and the development of aging-associated diseases. In irradiated mice, oncological pathology constituted 30-35% in the mortality structure, which is twice as often as in the control group. The developed model can be used to study the pathogenesis of accelerated aging under radiation exposure and the search for means of its prevention and treatment.

Use of Correct and Incorrect Methods of Accounting for Age in Studies of Epigenetic Accelerated Aging: Implications and Recommendations for Best Practices.

Motivated by our conduct of a literature review on social exposures and accelerated aging as measured by a growing number of epigenetic "clocks" (which estimate age via DNA methylation (DNAm) patterns), we report on 3 different approaches in the epidemiologic literature-1 incorrect and 2 correct-on the treatment of age in these and other studies using other common exposures (i.e., body mass index and alcohol consumption). Among the 50 empirical articles reviewed, the majority (n = 29; 58%) used the incorrect method of analyzing accelerated aging detrended for age as the outcome and did not control for age as a covariate. By contrast, only 42% used correct methods, which are either to analyze accelerated aging detrended for age as the outcome and control for age as a covariate (n = 16; 32%) or to analyze raw DNAm age as the outcome and control for age as a covariate (n = 5; 10%). In accord with prior demonstrations of bias introduced by use of the incorrect approach, we provide simulation analyses and additional empirical analyses to illustrate how the incorrect method can lead to bias towards the null, and we discuss implications for extant research and recommendations for best practices.

Analysis on in vitro effect of lithium on telomere length in lymphoblastoid cell lines from bipolar disorder patients with different clinical response to long-term lithium treatment.

BACKGROUND: It has been suggested that bipolar disorder (BD) is associated with clinical and biological features of accelerated aging. In our previous studies, we showed that long-term lithium treatment was correlated with longer leukocyte telomere length (LTL) in BD patients. A recent study explored the role of TL in BD using patients-derived lymphoblastoid cell lines (LCLs), showing that baseline TL was shorter in BD compared to controls and that lithium in vitro increased TL but only in BD. Here, we used the same cell system (LCLs) to explore if a 7-day treatment protocol with lithium chloride (LiCl) 1 mM was able to highlight differences in TL between BD patients clinically responders (Li-R; n = 15) or non-responders (Li-NR; n = 15) to lithium, and if BD differed from non-psychiatric controls (HC; n = 15). RESULTS: There was no difference in TL between BD patients and HC. Moreover, LiCl did not influence TL in the overall sample, and there was no difference between diagnostic or clinical response groups. Likewise, LiCl did not affect TL in neural precursor cells from healthy donors. CONCLUSIONS: Our findings suggest that a 7-day lithium treatment protocol and the use of LCLs might not represent a suitable approach to deepen our understanding on the role of altered telomere dynamics in BD as previously suggested by studies in vivo.

Nasal administration of mesenchymal stem cells prevents accelerated age-related tauopathy after chemotherapy in mice.

BACKGROUND: There is increasing concern that cancer and cancer treatment accelerate aging and the associated cognitive decline. We showed recently that treatment of 9-month-old male mice with cisplatin causes cognitive deficits that are associated with formation of tau deposits in the hippocampus. Here we explored the capacity of mesenchymal stem cells (MSC) given via the nose to prevent age-related brain tau deposits. Moreover, we more closely examined the cellular distribution of this hallmark of accelerated brain aging in response to treatment of 9-month-old female and male mice with cisplatin. RESULTS: We show that cisplatin induces tau deposits in the entorhinal cortex and hippocampus in both sexes. The tau deposits colocalize with syndecan-2. Astrocytes surrounding tau deposits have increased glial fibrillary acidic protein glial fibrillary acidic protein (GFAP) expression. Most of the cisplatin-induced tau deposits were located in microtubule associated protein-2 (MAP-2)+ neurons that were surrounded by aquaporin 4+ (AQP4)+ neuron-facing membrane domains of astrocytes. In addition, some tau deposits were detected in the perinuclear region of GFAP+ astrocytes and in CD31+ endothelial cells. There were no morphological signs of activation of ionized calcium binding adaptor molecule-1+ (Iba-1)+ microglia and no increases in brain cytokine production. Nasal administration of MSC at 48 and 96 hours after cisplatin prevented formation of tau deposits and normalized syndecan-2 and GFAP expression. Behaviorally, cisplatin-induced tau cluster formation was associated with reduced executive functioning and working/spatial memory and nasal administration of MSC at 48 and 96 hours after cisplatin prevented these cognitive deficits. Notably, delayed MSC administration (1 month after cisplatin) also prevented tau cluster formation and cognitive deficits, in both sexes. CONCLUSION: In summary, nasal administration of MSC to older mice at 2 days or 1 month after completion of cisplatin treatment prevents the accelerated development of tau deposits in entorhinal cortex and hippocampus and the associated cognitive deficits. Since MSC are already in clinical use for many other clinical indications, developing nasal MSC administration for treatment of accelerated brain aging and cognitive deficits in cancer survivors should be feasible and would greatly improve their quality of life.

U-shaped association between serum Klotho and accelerated aging among the middle-aged and elderly US population: a cross-sectional study.

BACKGROUND: Phenotypic age acceleration, which reflects the difference between phenotypic age and chronological age, is an assessment to measure accelerated aging. Klotho is a protein related to slower aging, but its association with accelerated aging remains unclear. METHODS: Based on data from the 2007-2010 National Health and Nutrition Examination Survey, phenotypic age was calculated using chronological age and 9 aging-related biomarkers. A total of 4388 participants aged 40 to 79 years with measured serum Klotho and calculated phenotypic age were enrolled. The association between serum Klotho and phenotypic age acceleration was estimated using multivariable linear regression models. The possible nonlinear relationship was examined with smooth curve fitting. We also conducted a segmented regression model to examine the threshold effect. RESULTS: The association between serum Klotho and phenotypic age acceleration followed a U-shaped curve (p for nonlinearity < 0.001), with the inflection point at 870.7 pg/ml. The phenotypic age acceleration significantly decreased with the increment of serum Klotho (per SD increment: ß -1.77; 95% CI, -2.57 ~ -0.98) in participants with serum Klotho < 870.7 pg/ml, and increased with the increment of serum Klotho (per SD increment:ß, 1.03; 95% CI: 0.53 ~ 1.54) in participants with serum Klotho ≥ 870.7 pg/ml. CONCLUSION: There was a U-shaped association between serum Klotho and accelerated aging among the middle-aged and elderly US population.

Long-Acting Real-Time Microscopic Monitoring Inside the Proton Exchange Membrane Water Electrolyzer.

The proton exchange membrane water electrolyzer (PEMWE) requires a high operating voltage for hydrogen production to accelerate the decomposition of hydrogen molecules so that the PEMWE ages or fails. According to the prior findings of this R&D team, temperature and voltage can influence the performance or aging of PEMWE. As the PEMWE ages inside, the nonuniform flow distribution results in large temperature differences, current density drops, and runner plate corrosion. The mechanical stress and thermal stress resulting from pressure distribution nonuniformity will induce the local aging or failure of PEMWE. The authors of this study used gold etchant for etching, and acetone was used for the lift-off part. The wet etching method has the risk of over-etching, and the cost of the etching solution is also higher than that of acetone. Therefore, the authors of this experiment adopted a lift-off process. Using the flexible seven-in-one (voltage, current, temperature, humidity, flow, pressure, oxygen) microsensor developed by our team, after optimized design, fabrication, and reliability testing, it was embedded in PEMWE for 200 h. The results of our accelerated aging test prove that these physical factors affect the aging of PEMWE.