Isotope Evidence for Rice Accumulation of Newly Deposited and Soil Legacy Cadmium: A Three-Year Field Study.

Biogeochemical processes of atmospherically deposited cadmium (Cd) in soils and accumulation in rice were investigated through a three-year fully factorial atmospheric exposure experiment using Cd stable isotopes and diffusive gradients in thin films (DGT). Our results showed that approximately 37-79% of Cd in rice grains was contributed by atmospheric deposition through root and foliar uptake during the rice growing season, while the deposited Cd accounted for a small proportion of the soil pools. The highly bioavailable metals in atmospheric deposition significantly increased the soil DGT-measured bioavailable fraction; yet, this fraction rapidly aged following a first-order exponential decay model, leading to similar percentages of the bioavailable fraction in soils exposed for 1-3 years. The enrichment of light Cd isotopes in the atmospheric deposition resulted in a significant shift toward lighter Cd isotopes in rice plants. Using a modified isotopic mass balance model, foliar and root uptake of deposited Cd accounted for 47-51% and 28-36% in leaves, 41-45% and 22-30% in stems, and 45-49% and 26-30% in grains, respectively. The implications of this study are that new atmospheric deposition disproportionately contributes to the uptake of Cd in rice, and managing emissions thus becomes very important versus remediation of impacted soils.

Predicting the evolution of clinical skin aging in a multi-ethnic population: Developing causal Bayesian networks using dermatological expertise.

INTRODUCTION: Software to predict the impact of aging on physical appearance is increasingly popular. But it does not consider the complex interplay of factors that contribute to skin aging. OBJECTIVES: To predict the +15-year progression of clinical signs of skin aging by developing Causal Bayesian Belief Networks (CBBNs) using expert knowledge from dermatologists. MATERIAL AND METHODS: Structures and conditional probability distributions were elicited worldwide from dermatologists with experience of at least 15 years in aesthetics. CBBN models were built for all phototypes and for ages ranging from 18 to 65 years, focusing on wrinkles, pigmentary heterogeneity and facial ptosis. Models were also evaluated by a group of independent dermatologists ensuring the quality of prediction of the cumulative effects of extrinsic and intrinsic skin aging factors, especially the distribution of scores for clinical signs 15 years after the initial assessment. RESULTS: For easiness, only models on African skins are presented in this paper. The forehead wrinkle evolution model has been detailed. Specific atlas and extrinsic factors of facial aging were used for this skin type. But the prediction method has been validated for all phototypes, and for all clinical signs of facial aging. CONCLUSION: This method proposes a skin aging model that predicts the aging process for each clinical sign, considering endogenous and exogenous factors. It simulates aging curves according to lifestyle. It can be used as a preventive tool and could be coupled with a generative AI algorithm to visualize aging and, potentially, other skin conditions, using appropriate images.

Effects of Melatonin on Liver of D-Galactose-Induced Aged Mouse Model.

Melatonin, a hormone secreted by the pineal gland of vertebrates, regulates sleep, blood pressure, and circadian and seasonal rhythms, and acts as an antioxidant and anti-inflammatory agent. We investigated the protective effects of melatonin against markers of D-galactose (D-Gal)-induced hepatocellular aging, including liver inflammation, hepatocyte structural damage, and non-alcoholic fatty liver. Mice were divided into four groups: phosphate-buffered saline (PBS, control), D-Gal (200 mg/kg/day), melatonin (20 mg/kg), and D-Gal (200 mg/kg) and melatonin (20 mg) cotreatment. The treatments were administered once daily for eight consecutive weeks. Melatonin treatment alleviated D-Gal-induced hepatocyte impairment. The AST level was significantly increased in the D-Gal-treated groups compared to that in the control group, while the ALT level was decreased compared to the melatonin and D-Gal cotreated group. Inflammatory genes, such as IL1-ß, NF-κB, IL-6, TNFα, and iNOS, were significantly increased in the D-Gal aging model, whereas the expression levels of these genes were low in the D-Gal and melatonin cotreated group. Interestingly, the expression levels of hepatic steatosis-related genes, such as LXRα, C/EBPα, PPARα, ACC, ACOX1, and CPT-1, were markedly decreased in the D-Gal and melatonin cotreated group. These results suggest that melatonin suppresses hepatic steatosis and inflammation in a mouse model of D-Gal-induced aging.

Deficient autophagy in epithelial stem cells drives aging in the freshwater cnidarian Hydra.

Hydra possesses three distinct stem cell populations that continuously self-renew and prevent aging in Hydra vulgaris However, sexual animals from the H. oligactis cold-sensitive strain Ho_CS develop an aging phenotype upon gametogenesis induction, initiated by the loss of interstitial stem cells. Animals stop regenerating, lose their active behaviors and die within 3 months. This phenotype is not observed in the cold-resistant strain Ho_CR To dissect the mechanisms of Hydra aging, we compared the self-renewal of epithelial stem cells in these two strains and found it to be irreversibly reduced in aging Ho_CS but sustained in non-aging Ho_CR We also identified a deficient autophagy in Ho_CS epithelial cells, with a constitutive deficiency in autophagosome formation as detected with the mCherry-eGFP-LC3A/B autophagy sensor, an inefficient response to starvation as evidenced by the accumulation of the autophagosome cargo protein p62/SQSTM1, and a poorly inducible autophagy flux upon proteasome inhibition. In the non-aging H. vulgaris animals, the blockade of autophagy by knocking down WIPI2 suffices to induce aging. This study highlights the essential role of a dynamic autophagy flux to maintain epithelial stem cell renewal and prevent aging.

D-Galactose-induced oxidative stress and mitochondrial dysfunction in the cochlear basilar membrane: an in vitro aging model.

The cochlear basilar membrane (CBM) contains inner hair cells and outer hair cells that convert sound waves into electrical signals and transmit them to the central auditory system. Cochlear aging, the primary reason of age-related hearing loss, can reduce the signal transmission capacity. There is no ideal in vitro aging model of the CBM. In this study, we cultured the CBM, which was dissected from the cochlea of the C57BL/6 mice 5 days after birth, in a medium containing 20 mg/mL, 40 mg/mL, or 60 mg/mL D-galactose (D-gal). Compared with the control group, the levels of senescence-associated ß-galactosidase were increased in a concentration-dependent manner in the CBM of the D-gal groups. In addition, levels of the mitochondrial superoxide and patterns of an age-related mitochondrial DNA3860-bp deletion were significantly increased. The ATP levels and the membrane potential of the mitochondrial were significantly decreased in the CBM of the D-gal groups compared with the control group. Furthermore, in comparison with the control group, damaged hair cell stereocilia and a loss of inner hair cell ribbon synapses were observed in the CBM of the D-gal groups. A loss of hair cells and activation of caspase-3-mediated outer hair cell apoptosis were also observed in the CBM of the high-dose D-gal group. These insults induced by D-gal in the CBM in vitro were similar to the ones that occur in cochlear natural aging in vivo. Thus, we believe that this is a successful in vitro aging model using cultured CBM. These results demonstrate the effects of mitochondrial oxidative damage on presbycusis and provide a reliable aging model to study the mechanisms of presbycusis in vitro.

D-Galactose-induced accelerated aging model: an overview.

To facilitate the process of aging healthily and prevent age-related health problems, efforts to properly understand aging mechanisms and develop effective and affordable anti-aging interventions are deemed necessary. Systemic administration of D-galactose has been established to artificially induce senescence in vitro and in vivo as well as for anti-aging therapeutic interventions studies. The aim of this article is to comprehensively discuss the use of D-galactose to generate a model of accelerated aging and its possible underlying mechanisms involved in different tissues/organs.

Aging of target lipid parameters in fingermark residue using GC/MS: Effects of influence factors and perspectives for dating purposes.

Despite the recurrence of fingermark dating issues and the research conducted on fingermark composition and aging, no dating methodology has yet been developed and validated. In order to further evaluate the possibility of developing dating methodologies based on the fingermark composition, this research proposed an in-depth study of the aging of target lipid parameters found in fingermark residue and exposed to different influence factors. The selected analytical technique was gas chromatography coupled with mass spectrometry (GC/MS). The effects of donor, substrate and enhancement techniques on the selected parameters were firstly evaluated. These factors were called known factors, as their value could be obtained in real caseworks. Using principal component analysis (PCA) and univariate exponential regression, this study highlighted the fact that the effects of these factors were larger than the aging effects, thus preventing the observation of relevant aging patterns. From a fingermark dating perspective, the specific value of these known factors should thus be included in aging models newly built for each case. Then, the effects of deposition moment, pressure, temperature and lighting were also evaluated. These factors were called unknown factors, as their specific value would never be precisely obtained in caseworks. Aging models should thus be particularly robust to their effects and for this reason, different chemometric tools were tested: PCA, univariate exponential regression and partial least square regression (PLSR). While the first two models allowed observing interesting aging patterns regardless of the value of the applied influence factors, PLSR gave poorer results, as large deviations were obtained. Finally, in order to evaluate the potential of such modelling in realistic situations, blind analyses were carried out on eight test fingermarks. The age of five of them was correctly estimated using soft independent modelling of class analogy analysis (SIMCA) based on PCA classes, univariate exponential linear regression and PLSR. Furthermore, a probabilistic approach using the calculation of likelihood ratios (LR) through the construction of a Bayesian network was also tested. While the age of all test fingermarks were correctly evaluated when the storage conditions were known, the results were not significant when these conditions were unknown. Thus, this model clearly highlighted the impact of storage conditions on correct age evaluation. This research showed that reproducible aging modelling could be obtained based on fingermark residue exposed to influence factors, as well as promising age estimations. However, the proposed models are still not applicable in practice. Further studies should be conducted concerning the impact of influence factors (in particular, storage conditions) in order to precisely evaluate in which conditions significant evaluations could be obtained. Furthermore, these models should be properly validated before any application in real caseworks could be envisaged.

Splenocyte proliferation and anaphylaxis induced by BSA challenge in a D-galactose-induced aging mouse model.

We previously found a cross-reactive autoantibody that bound to bovine serum albumin generated in a D-galactose-induced aging mouse model. Also, we confirmed that other reducing sugars (glucose and fructose) could induce the formation of autoantibody, and only following subcutaneous injection, not oral or intraperitoneal administration. Mice that had never been exposed to bovine serum albumin produced an anti-bovine serum albumin autoantibody following repeated subcutaneous injection of D-galactose (D-gal). In this study, we investigated the involvement of the adaptive immune system in the production of this autoantibody. In particular, we examined bovine serum albumin-induced splenocyte proliferation and bovine serum albumin-induced active cutaneous and systemic anaphylaxis in D-gal-treated mice. We find our results particularly interesting: bovine serum albumin stimulates splenocyte proliferation and induces both active cutaneous and systemic anaphylaxis in D-gal-treated mice. In summary, our results suggest that adaptive immune response participates in the autoantibody formation against bovine serum albumin in D-gal-treated mice.

A semi-mechanistic aging model of Pb added to soil by a modified stable isotope dilution technique.

The aging of Pb added to soils has not been studied by the isotopic technology because of difficulties in determination of isotopically exchangeable Pb in soil, so that a set of 10 typical agricultural soils in China and a one-year aging experiment with the addition of water-soluble Pb to the soils were carried out. A modified stable isotope dilution technique to determine isotopically exchangeable Pb in soil was developed where 0.2 mM EDTA (ethylenediaminetetraacetic acid) as the extractant. When water-soluble Pb was added to soil, the isotopically exchangeable Pb (Eadd%, the percentage of isotopically exchangeable Pb to total Pb added to soil) initially decreased rapidly and gradually slowly. A semi-mechanistic aging model of Pb added to soils, including precipitation/nucleation (Y1), micropore diffusion (Y2), and organic matter encapsulation processes (Y3) was developed with the root mean square error 8.3% where Y1, Y2, and Y3 accounted for 0.02~26.9%, 1.4~21.8% and 3.8~11.3%, respectively, when the pH 4.0~8.0 and organic matter 2.0~6.0%. Soil pH was a vital factor affecting the aging rate. When the pH increased by 1 unit, the Eadd value decreased by approximately 9%. The model could be used to scale ecotoxicological data of Pb in soil generated in different aging times.

Omega-3-Enriched Diet Improves Metabolic Profile in Prdx6-Deficient Mice Exposed to Microgravity.

BACKGROUND: Space travel has always been one of mankind's greatest dreams. Thanks to technological innovation, this dream is becoming more of a reality. Soon, humans (not only astronauts) will travel, live, and work in space. However, a microgravity environment can induce several pathological alterations that should be, at least in part, controlled and alleviated. Among those, glucose homeostasis impairment and insulin resistance occur, which can lead to reduced muscle mass and liver dysfunctions. Thus, it is relevant to shed light on the mechanism underlaying these pathological conditions, also considering a nutritional approach that can mitigate these effects. METHODS: To achieve this goal, we used Prdx6-/- mice exposed to Hindlimb Unloading (HU), a well-established experimental protocol to simulate microgravity, fed with a chow diet or an omega-3-enriched diet. RESULTS: Our results innovatively demonstrated that HU-induced metabolic alterations, mainly related to glucose metabolism, may be mitigated by the administration of omega-3-enriched diet. Specifically, a significant improvement in insulin resistance has been reported. CONCLUSIONS: Although preliminary, our results highlight the importance of specific nutritional approaches that can alleviate microgravity-induced harmful effects. These findings should be considered soon by those planning trips around the earth.

Hippocampal glial inflammatory markers are differentially altered in a novel mouse model of perimenopausal cerebral amyloid angiopathy.

Dementia is often characterized by age-dependent cerebrovascular pathology, neuroinflammation, and cognitive deficits with notable sex differences in risk, disease onset, progression and severity. Women bear a disproportionate burden of dementia, and the onset of menopause (i.e., perimenopause) may be a critical period conferring increased susceptibility. However, the contribution of early ovarian decline to the neuroinflammatory processes associated with cerebrovascular dementia risks, particularly at the initial stages of pathology that may be more amenable to proactive intervention, is unknown. To better understand the influence of early ovarian failure on dementia-associated neuroinflammation we developed a model of perimenopausal cerebral amyloid angiopathy (CAA), an important contributor to dementia. For this, accelerated ovarian failure (AOF) was induced by 4-vinylcyclohexene diepoxide (VCD) treatment to isolate early-stage ovarian failure comparable to human perimenopause (termed "peri-AOF") in transgenic SWDI mice expressing human vasculotropic mutant amyloid beta (Aß) precursor protein, that were also tested at an early stage of amyloidosis. We found that peri-AOF SWDI mice showed increased astrocyte activation accompanied by elevated Aß in select regions of the hippocampus, a brain system involved in learning and memory that is severely impacted during dementia. However, although SWDI mice showed signs of increased hippocampal microglial activation and impaired cognitive function, this was not further affected by peri-AOF. In sum, these results suggest that elevated dysfunction of key elements of the neurovascular unit in select hippocampal regions characterizes the brain pathology of mice at early stages of both CAA and AOF. However, neurovascular unit pathology may not yet have passed a threshold that leads to further behavioral compromise at these early periods of cerebral amyloidosis and ovarian failure. These results are consistent with the hypothesis that the hormonal dysregulation associated with perimenopause onset represents a stage of emerging vulnerability to dementia-associated neuropathology, thus providing a selective window of opportunity for therapeutic intervention prior to the development of advanced pathology that has proven difficult to repair or reverse.

The potential of Andaliman (Zanthoxylum acanthopodium DC) fruit as an ethanol extract for neuroprotection in aged model rat.

Objective: Dementia is a common aging-related neurodegenerative disease in the elderly worldwide. Alterations in neurogenesis and angiogenesis factors have been linked to cognitive impairment in neurological disorders. However, synthetic drugs to improve memory disorders have uncomfortable side effects. The purpose of this study is to explore the neuroprotective potential of the fruit ethanol extract of andaliman (Zanthoxylum acanthopodium DC) [Andaliman fruit ethanol extract (AEE)] on brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), and spatial memory in rat models of aging. Materials and Methods: This study had an experimental design with AEE. The 4 groups were treated as follows: N (normal), M (served as positive control), P1 (AEE 150 mg/kg bw), and P2 (AEE 300 mg/kg BW) for 8 weeks. Aged model rats (M, P1, and P2) were obtained by inducing D-galactose (150 mg/kg bw). BDNF and VEGF expression were determined by RT-PCR, and spatial memory was assessed using the test of the Moris Water Maze (MWM). The Kruskal-Wallis and Mann-Whitney tests were used to assess the statistical analysis. Results: AEE had a tendency to increase BDNF in P2 compared to the normal group (1.98 versus 1). VEGF expression increased in P1 and P2 compared to the normal group (1.14 and 1.29 versus 1). AEE at a dose of 300 mg/kg bw significantly improved spatial memory (p = 0.026). Conclusion: For eight weeks, AEE at a dose of 300 mg/kg bw considerably increased the potential to enhance VEGF and BDNF expression as well as spatial memory.

Cross-sectionally Calculated Metabolic Aging Does Not Relate to Longitudinal Metabolic Changes-Support for Stratified Aging Models.

CONTEXT: Aging varies between individuals, with profound consequences for chronic diseases and longevity. One hypothesis to explain the diversity is a genetically regulated molecular clock that runs differently between individuals. Large human studies with long enough follow-up to test the hypothesis are rare due to practical challenges, but statistical models of aging are built as proxies for the molecular clock by comparing young and old individuals cross-sectionally. These models remain untested against longitudinal data. OBJECTIVE: We applied novel methodology to test if cross-sectional modeling can distinguish slow vs accelerated aging in a human population. METHODS: We trained a machine learning model to predict age from 153 clinical and cardiometabolic traits. The model was tested against longitudinal data from another cohort. The training data came from cross-sectional surveys of the Finnish population (n = 9708; ages 25-74 years). The validation data included 3 time points across 10 years in the Young Finns Study (YFS; n = 1009; ages 24-49 years). Predicted metabolic age in 2007 was compared against observed aging rate from the 2001 visit to the 2011 visit in the YFS dataset and correlation between predicted vs observed metabolic aging was determined. RESULTS: The cross-sectional proxy failed to predict longitudinal observations (R2 = 0.018%, P = 0.67). CONCLUSION: The finding is unexpected under the clock hypothesis that would produce a positive correlation between predicted and observed aging. Our results are better explained by a stratified model where aging rates per se are similar in adulthood but differences in starting points explain diverging metabolic fates.

Theaflavin-3,3'-digallate ameliorates learning and memory impairments in mice with premature brain aging induced by D-galactose.

Age-related neurodegenerative diseases accompanied by learning and memory deficits are growing in prevalence due to population aging. Cellular oxidative stress is a common pathomechanism in multiple age-related disorders, and various antioxidants have demonstrated therapeutic efficacy in patients or animal models. Many plants and plant extracts possess potent antioxidant activity, but the compounds responsible are frequently unknown. Identification and evaluation of these phytochemicals is necessary for optimal targeted therapy. A recent study identified theaflavin-3,3'-digallate (TFDG) as the most potent among a large series of phytochemical antioxidants. Here we examined if TFDG can mitigate learning and memory impairments in the D-galactose model of age-related neurodegeneration. Experimental mice were injected subcutaneously with D-galactose (120 mg/kg) for 56 days. In treatment groups, different doses of TFDG were administered daily by gavage starting on day 29 of D-galactose injection. Model mice exhibited poor learning and memory in the novel object recognition and Y-maze tests, reduced brain/body mass ratio, increased brain glutamate concentration and acetylcholinesterase activity, decreased brain acetylcholine concentration, and lower choline acetyltransferase, glutaminase, and glutamine synthetase activities. Activities of antioxidant enzymes glutathione peroxidase and superoxide dismutase were also reduced, while the concentration of malondialdehyde, a lipid peroxidation product, was elevated. Further, antioxidant genes Nrf2, Prx2, Gsh-px1, and Sod1 were downregulated in brain. Each one of these changes was dose-dependently reversed by TFDG. TFDG is an effective antioxidant response inducer and neuroprotectant that can restore normal neurotransmitter metabolism and ameliorate learning and memory dysfunction in the D-galactose model of age-related cognitive decline.

Establishment of Reference Interval and Aging Model of Homocysteine Using Real-World Data.

Objective: The level of Homocysteine (Hcy) in males is generally higher than that of females, but the same reference interval (RI) is often used in clinical practice. This study aims to establish a sex-specific RI of Hcy using five data mining algorithms and compare these results. Furthermore, age-related continuous RI was established in order to show the relationship between Hcy concentration distribution and age. Methods: A total of 20,801 individuals were included in the study and Tukey method was used to identify outliers in subgroups by sex and age. Multiple linear regression and standard deviation ratio (SDR) was used to determine whether the RI for Hcy needs to be divided by sex and age. Five algorithms including Hoffmann, Bhattacharya, expectation maximization (EM), kosmic and refineR were utilized to establish the RI of Hcy. Generalized Additive Models for Location Scale and Shape (GAMLSS) algorithm was used to determine the aging model of Hcy and calculate the age-related continuous RI. Results: RI of Hcy needed to be partitioned by sex (SDR = 0.735 > 0.375). RIs established by Hoffmann, Bhattacharya, EM (for females) and kosmic are all within the 95% CI of reference limits established by refine R. The Sex-specific aging model of Hcy showed that the upper limits of the RI of Hcy declined with age beginning at age of 18 and began to rise approximately after age of 40 for females and increased with age for males. Conclusion: The RI of Hcy needs to be partitioned by sex. The RIs established by the five data mining algorithms showed good consistency. The dynamic sex and age-specific model of Hcy showed the pattern of Hcy concentration with age and provide more personalized tools for clinical decisions.

D-Galactose-Induced Accelerated Aging Model on Auditory Cortical Neurons by Regulating Oxidative Stress and Apoptosis in Vitro.

OBJECTIVES: Age-related hearing loss (ARHL) is much more prevalent with age, affecting not only peripheral but central auditory system. We have previously established an aging model of peripheral auditory system in vitro using cultured cochlear basilar membrane. However, there is no ideal accelerated aging model on central auditory system in vitro. To establish the aging model, auditory cortical neurons (ACNs) were primary cultured and treated with either vehicle or different doses of D-galactose (D-gal). We studied the effect of D-gal on ACNs by evaluating the hallmarks of aging, including cell proliferation, oxidative stress, mitochondrial function, and neuronal apoptosis. Compared with the control group, cell viability was significantly inhibited in the D-gal-treated group in a dose-dependent manner. The production of reactive oxygen species was strongly increased in the D-gal-treated group. Meanwhile, the level of 8-hydroxy-2'-deoxyguanosine, which is a biomarker of DNA oxidative damage, was even higher in the D-gal-treated group than that in the control group. Conversely, the levels of ATP and mitochondrial membrane potential were notably decreased in the D-gal-treated group contrast to that in the control group. Furthermore, the number of neuronal apoptosis in the D-gal-treated group, compared with that in the control group, was dramatically increased in a dose-dependent approach. Together, our results demonstrate that ACNs treated with D-gal in vitro display senescence characteristics by regulating oxidative stress and apoptosis, indicating accelerated aging model on ACNs are successfully established. And the model provides a promising approach for exploring underlying mechanisms of the ARHL.

Anti-Aging Activity of Andaliman (Zanthoxylum Acanthopodium DC) Fruit Ethanol Extract on Brain Weight and p16INK4a Expression of Hippocampus in Aging Model Rats.

Background: Physiological aging and due to oxidative stress in long term will have an impact on cellular response disorders, can caused aging of hippocampus and senility. Brain weight is known to decrease with age and p16INK4a as aging biomarkers have been investigated. Andaliman is one of typical herbal plants from North Sumatra has been widely used as an antioxidant, anti-inflammatory and anti-aging. Objective: This study was evaluated effect of andaliman (Zanthoxylum acanthopodium DC) fruit ethanol extract (AEE) on brain weight and p16INK4a expression in aging model rats. Methods: This study was carried out experimentally of 24 male wistar rats. The treatment group consisted of 4 groups; KN= negatif control (normal), KP= positif control (aging model rat), P1 and P2= aging model rat + AEE at dose 150 and 300mg/kgbw, respectively. The aging model rats were D-galactose-induced at dose of 150mg/kgbw for 8 weeks. Brain weigth were recorded by digital scales. p16INK4a expression using immunohistochemical methods. The data analysis with Anova test. Results: This study showed differences brain weight between groups (p=0.523). Brain weight in P1 (1.34±0,06) and P2 (1.30±0.09) tendency increased than KP (1.29±0.62). The p16INK4a expression between groups significant difference (p=0.041), continued with post hoc Least Significant Difference (LSD) showed p16INK4a expression in KN significant decreased than KP (p=0.027). Likewise, p16INK4a expression in P2 was significant decreased than KP (p=0.010). Conclusion: Andaliman ethanol extract at a dose 300mg/kgbw for 8 weeks was improved aging process caused D-galactose induced.

Associations of Circulating Insulin-Growth Factor-1 With Cognitive Functions and Quality of Life Domains in Ambulatory Young Adults With Cerebral Palsy: A Pilot Study.

Objective: Adults with cerebral palsy (CP) often have impaired cognitive functions. CP also has deteriorations in multiple quality-of-life (QoL) domains. The bio-psycho-social health psychology model posits that biological factor interacts with social and psychological functions. However, the biological determinant of psycho-social and functional outcomes in CP has been scarcely examined. Circulating Insulin-like growth factor-1 (IGF-1) is associated with cognitive deficits in older adults, we thus aimed to examine the associations of circulating IGF-1 with: (1) objectively measured cognitive functions, (2) self-reported cognitive functions, and (3) QoL measures in adults diagnosed with CP. Methods: Seventy-two adults with CP and varying degrees of cognitive functions were recruited from an accredited clinical motion analysis laboratory at a regional Children's Hospital. Circulating IGF-1 was measured using post-fasting serum. The Wechsler Adult Intelligence Scale (WAIS) tests were administered to assess multiple cognitive functions, whereas the Patient-Reported Outcomes Measurement Information System (PROMIS) was used to measure multiple domains of self-reported health, including cognitive complaints and eight QoL domains. Results: Sixty-eight participants had complete data [mean age = 25 (SD = 5.3), female = 52.8%]. Controlling for covariates, circulating IGF-1 was associated with multiple cognitive domains, including positively with declarative memory and executive function and inversely with visual-spatial and motor skills, and processing speed, while no association with subjective memory complaint was detected. Circulating IGF-1 was also inversely associated with four QoL domains, including depressive symptoms, executive function, physical function, and social roles and activities. Conclusions: In CP, circulating IGF-1 might be a useful biological determinant of objective cognitive functions and several quality-of-life domains commonly impaired in CP.

Fisetin Rescues the Mice Brains Against D-Galactose-Induced Oxidative Stress, Neuroinflammation and Memory Impairment.

Herein, we have evaluated the protective potentials of Fisetin against d-galactose-induced oxidative stress, neuroinflammation, and memory impairment in mice. d-galactose (D-gal) causes neurological impairment by inducing reactive oxygen species (ROS), neuroinflammation, and synaptic dysfunction, whereas fisetin (Fis) is a natural flavonoid having potential antioxidant effects, and has been used against different models of neurodegenerative diseases. Here, the normal mice were injected with D-gal (100 mg/kg/day for 60 days) and fisetin (20 mg/kg/day for 30 days). To elucidate the protective effects of fisetin against d-galactose induced oxidative stress-mediated neuroinflammation, we conducted western blotting, biochemical, behavioral, and immunofluorescence analyses. According to our findings, D-gal induced oxidative stress, neuroinflammation, synaptic dysfunctions, and cognitive impairment. Conversely, Fisetin prevented the D-gal-mediated ROS accumulation, by regulating the endogenous anti-oxidant mechanisms, such as Sirt1/Nrf2 signaling, suppressed the activated p-JNK/NF-kB pathway, and its downstream targets, such as inflammatory cytokines. Hence, our results together with the previous reports suggest that Fisetin may be beneficial in age-related neurological disorders.

Features of T-cell subset composition in a D-galactose-induced senescence mouse model.

Long-term administration of D-galactose induces oxidative stress and accelerates normal age-related changes. Hence, the D-galactose-treated rodent model has been widely used for aging research. In this study, we examined the immunological characteristics, especially CD4+ T-cell subset composition, of D-galactose-induced aging model mice to evaluate the model's utility in immunosenescence studies. The spleens of aging model mice subjected to repeated subcutaneous injections of D-galactose exhibited significant increases in T cells with the memory phenotype (CD62Llow CD44high) and individual T-cell subsets (Th1, Th2, Th17 and Treg). Furthermore, cells with the phenotype of T follicular helper (Tfh) cells were spontaneously increased. The features of T-cell subset composition in D-galactose-treated mice were in close agreement with those observed in normal aged mice and appeared to mimic the currently known normal aging processes associated with T-cell homeostasis. Our results suggest that D-galactose-induced aging models would be useful for immunosenescence studies focusing on T-cell homeostasis and give valuable insight into age-related immune system dysregulation.