Age-related Differences In Response Research Articles

Age-Related Response to Remimazolam among Older Patients Undergoing Orthopedic Surgery: A Single-Center Prospective Observational Study.

Background and Objectives: Remimazolam, an ultra-short-acting benzodiazepine, is increasingly used in procedural sedation and general anesthesia. It is characterized by rapid onset of action, inactive metabolites, no delay in recovery, and few adverse events. Its hemodynamic and respiratory stability are comparable to other anesthetics, and it is safe in high-risk and geriatric patients. Materials and Methods: This prospective, observational study enrolled 110 geriatric patients (aged 65 to 85 years) scheduled for primary total knee arthroplasty (TKA). The patients were divided into the old (65 to <75 years; n = 52) and the elderly (75 to 85 years; n = 47) geriatric groups. All surgical and anesthetic methods were applied in the same manner, and TKA was performed by one surgeon. Remimazolam was infused at 6 mg/kg/h for 3 min and then at 1 mg/kg/h until the end of surgery The primary study endpoint was the requirement for flumazenil; secondary endpoints were the times to reach a bispectral index (BIS) < 60 and >80, as well as the rate of apnea occurrence. Results: Flumazenil administration was similar in both groups. There were no differences in the time to reach BIS < 60 or the rate of apnea occurrence. Recovery characteristics, including the time to reach BIS > 80 and the achievement of full consciousness, were also comparable between the groups. Conclusions: Remimazolam is well-tolerated in geriatric patients undergoing orthopedic surgery, with minimal age-related differences in response. These results suggest that remimazolam is an appropriate anesthetic for geriatric patients, even with similar dosing strategies. It provides effective anesthetic depth with no significant increases in adverse outcomes during orthopedic surgery.

Difficulty sensitivity replaces reward sensitivity during adolescence: Task-related fMRI and functional connectivity during self-regulative learning choices

AimWe examined age-related differences in valuation and cognitive control circuits during value-based decision-making. Methods13-year-olds (N = 25) and 17-year-olds (N = 22) made a metacognitive choice to be tested or not on an upcoming learning task, based on reward and difficulty associated with word-pairs. To investigate whether these determinants of subjective value are differently processed at different ages, we performed region-of-interest(ROI)-based analyses of task-related and functional connectivity data.Results: We observed age-related differences in responsiveness of valuation structures (amygdala, ventral striatum, ventromedial prefrontal cortex) and caudate nucleus, with activity modulated by reward in 13-year-olds, while in 17-year-olds activity being responsive to difficulty. These accompanied age-related differences in functional connectivity between medial prefrontal and striatal/amygdala seeds. DiscussionThese results are in line with current views that sensitivity changes for reward and difficulty during adolescence are the result of a maturational switch in effort-related signalling in the cognitive control circuit, which increasingly regulates value-signalling structures.

Age-related differences in response to plasma exchange in male rat liver tissues: insights from histopathological and machine-learning assisted spectrochemical analyses.

This study aimed to examine the biological effects of blood plasma exchange in liver tissues of aged and young rats using machine learning methods and spectrochemical and histopathological approaches. Linear Discriminant Analysis (LDA) and Support Vector Machine (SVM) were the machine learning algorithms employed. Young plasma was given to old male rats (24months), while old plasma was given to young male rats (5weeks) for thirty days. LDA (95.83-100%) and SVM (87.5-91.67%) detected significant qualitative changes in liver biomolecules. In old rats, young plasma infusion increased the length of fatty acids, triglyceride, lipid carbonyl, and glycogen levels. Nucleic acid concentration, phosphorylation, and carbonylation rates of proteins were also increased, whereas a decrease in protein concentration was measured. Aged plasma decreased protein carbonylation, triglyceride, and lipid carbonyl levels. Young plasma infusion improved hepatic fibrosis and cellular degeneration and reduced hepatic microvesicular steatosis in aged rats. Otherwise, old plasma infusion in young rats caused disrupted cellular organization, steatosis, and increased fibrosis. Young plasma administration increased liver glycogen accumulation and serum albumin levels. Aged plasma infusion raised serum ALT levels while diminished ALP concentrations in young rats, suggesting possible liver dysfunction. Young plasma increased serum albumin levels in old rats. The study concluded that young plasma infusion might be associated with declined liver damage and fibrosis in aged rats, while aged plasma infusion negatively impacted liver health in young rats. These results imply that young blood plasma holds potential as a rejuvenation therapy for liver health and function.

Age-Related Differences in Responses to Social Exclusion: Active Regulation Matters.

Although previous studies have reached a consensus that older adults have weaker responses to social exclusion than younger adults, the underlying mechanism is still under debate. The present study examined the age-related differences in responses toward social exclusion with self-report scales and electrodermal activity measurements, aiming at a further understanding of the possible mechanism behind these behaviors. Sixty-nine younger (aged 16-28, Mage = 20.13) and 71 older adults (aged 55-82, Mage = 66.72) completed a Cyberball task to simulate social exclusion. They were then asked to regulate the exclusion experiences with different strategies (affect-focused attention/detached reappraisal/distraction strategies) in a subsequent regulation session. Their electrodermal activities were measured throughout the entire process. Self-report scales were measured after the Cyberball session and at the end of the regulation session. Similar to previous studies, older adults exhibited a lower level of responsiveness toward social exclusion in both self-report scales and electrodermal activities. Moreover, during the Cyberball session, older adults exhibited a tendency of increased electrodermal activity, followed by a decrease in activity. Younger adults demonstrated a pattern of continuous increase. In the regulation session, younger adults from the detached reappraisal regulation strategy condition mimicked the overall response pattern of older adults, such that they exhibited lower levels of responsiveness toward social exclusion. The results from the present study indicate that active emotion regulation (i.e., detached reappraisal) in appraisal stage rather than declined cognition might account for the age-related differences in responses toward social exclusion between older and younger adults.

Abstract 135: Age-related immunosenescence and cancer drug toxicity and efficacy in C57BL/6J syngeneic model

Abstract Cancer has a higher incidence in the elderly and immunotherapy is widely applied to this population. However, the majority of preclinical studies assessing drug toxicity and efficacy have been done in young healthy mice. Immunosenescence is a state of aging-related gradual deterioration of the immune system in the elderly. Here, we established tumor models in aged mice that show immunosenescence for a better representation of cancer patients, and to examine the effects of aging and immunosenescence on cancer drug efficacy and toxicity. Young (7 weeks), mid-aged (54-58 weeks), and aged (76-78 weeks) C57BL/6J female mice were used for this study. Syngeneic tumor models were established using three different mouse cancer cell lines, B16-F10 melanoma, MC38 colon adenocarcinoma, and E0771 breast cancer. Age-related tumor growth kinetics varied based on tumor models. Specifically, aging did not affect tumor growth kinetics of B16-F10 tumors, while aged mice showed slowed growth of MC38 tumors and faster growth of E0771 tumors. To evaluate the maximum tolerated dose, young and aged mice were dosed with the standard of care cancer drugs (docetaxel, cisplatin, and doxorubicin) and body weight was monitored three times a week. Aged mice showed higher toxicity against standard care cancer drugs compared to young counterparts. Next, we performed efficacy study using checkpoint inhibitor. Young, mid-aged, and aged mice bearing MC-38 tumor were treated with isotype control or Anti-PD1 (8 mg/kg), intravenously, twice weekly for 3 weeks. Whole blood and tumor samples were collected for immune cell profiling. Comparisons of PD-1 response in the various age groups showed that anti-PD1 treatment showed significant suppression of tumor growth in all age groups with the MC38 tumors, with the greatest effect in aged mice. We also found that anti-PD1 treatment increased T cell infiltration into the tumor, and that regulatory T cells in the tumor are decreased in aged mice. In conclusion, we established syngeneic tumor models using aged mice, and found aged mice exhibit higher toxicity against drugs. The effect of aging on tumor growth kinetics varies depending on the models. Differences in immune cell infiltration in the tumor might be an underlying event that causes age-related differences in response to anti-PD1 treatment. The integration of aging in cancer research could potentially bridge the gap between preclinical studies and clinical outcomes. Citation Format: Jiwon Yang, Andrew Schile, Mingshan Cheng, James G. Keck. Age-related immunosenescence and cancer drug toxicity and efficacy in C57BL/6J syngeneic model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 135.

Observed shyness leads to more automatic imitation in early childhood.

The authors investigated children's automatic imitation in the context of observed shyness by adapting the widely used automatic imitation task (AIT). AIT performance in 6-year-old children (N=38; 22 female; 71% White) and young adults (17-22 years; N=122; 99 female; 32% White) was first examined as a proof of concept and to assess age-related differences in responses to the task (Experiment 1). Although error rate measures of automatic imitation were comparable between children and adults, children displayed less reaction time interference than adults. Children's shyness coded from direct behavioral observations was then examined in relation to AIT scores (Experiment 2). Observed shyness at 5 years old predicted higher automatic imitation one year later. We discuss the latter findings in the context of an adaptive strategy. We argue that shy children may possess a heightened sensitivity to others' motor cues and therefore are more likely to implicitly imitate social partners' actions. This tendency may serve as a strategy to signal appeasement and affiliation, allowing for shy children to blend in and feel less inhibited in a social environment.

Age differences in neural response to reward and loss in children.

The goal of this study was to examine age-related differences in children's reward processing. Focusing on reward outcome processing, we used event-related potentials to examine substages of neural response to gain versus loss feedback in a sample of 7-11-year-old children (M=9.67, SD=1.40) recruited from the community (N=234; 47.6% girls, 66.2% non-Hispanic European American). Using principal components analysis (PCA), we focused on temporospatial combinations that closely resembled the RewP, fb-P3, and fb-LPP in temporal and spatial distributions. Two of these, the PCA factors reflecting the RewP and fb-LPP, demonstrated age-related differences in response to gains versus losses. Age-related changes in the RewP were specific to gain feedback, with RewP amplitudes to gain, but not loss, increasing from middle to late childhood. In contrast, age-related changes in fb-LPP were specific to loss feedback, with fb-LPP amplitudes to losses, but not gains, decreasing from middle to late childhood. Follow-up analyses revealed that children younger than age 8 exhibited larger fb-LPP responses to loss than gain, whereas children older than age 10 exhibited larger RewP responses to gain than loss. Similar results were obtained using mean amplitude-based ERP indices and the results do not appear to have been due to age-related differences in the latency or location of the ERPs themselves. These results highlight the importance of examining distinct substages of reward outcome processing and suggest that robust neural responses to loss feedback may emerge earlier in childhood than responses to gains.

Dysphagia-Related Health Information Improved Consumer Acceptability of Thickened Beverages

Most people tend to think that healthy foods do not taste good. This view could have a negative impact on the taste of the food that people eat for health. However, if health-related information is provided to avoid negative aspects, acceptability may improve. Thus, this study investigated changes in consumers’ sensory perception of thickened beverages before and after the provision of dysphagia-related health information. Sixty young (19–39 years old) and middle-aged (40–64 years old) consumers participated in two experiment sessions conducted one week apart. The first session proceeded without any information and the second provided information about dysphagia and the need for dietary modification before evaluation. Three beverages (orange juice, red bean water, and sports drink) were used in nectar-like (51–350 cP) and honey-like (351–1750 cP) forms; original beverage samples (0%) were used as the control. Consumers were asked about acceptability, liking the flavor, intensity, and general health interest (GHI). An analysis of variance was performed to show the change in flavor rating and acceptability between the two sessions. Although there were age-related differences in response to the samples, thickened beverages were rated as more acceptable, in terms of their characteristics (swallowing, viscosity, and mouthfeel) after the information was provided. There were no significant differences for the 0% samples. The mean GHI values were 3.97 ± 0.85 and 4.81 ± 0.68 for the young and middle-aged groups, respectively. High and low GHI groups were analyzed. The high GHI group showed significant differences in acceptability in the informed evaluation, whereas the low GHI group was not influenced by the information.

Multi-omics reveals age-related differences in the diaphragm response to mechanical ventilation: a pilot study

BackgroundOld age is associated with a significantly increased mortality in COVID-19 patients exposed to long-term controlled mechanical ventilation (CMV) and suggested to be due to the hyperinflammatory response associated with the viral infection. However, our understanding of age-related differences in the response to CMV in the absence of a viral infection remains insufficient.MethodsYoung (7–8 months) and old (28–32 months) F344 BN hybrid rats were exposed to the ICU condition for 5 days, i.e., complete immobilization, mechanical ventilation, and extensive monitoring. Transcriptomic (RNA-Seq) and proteomics (Proximity Extension Assay) analyses of the diaphragm and proteomics analysis of plasma were conducted to investigate the molecular differences between young and old rats exposed to the ICU condition.ResultsAccording to multi-omics analyses, significant differences were observed in the diaphragm between young and old rats in response to 5 days CMV and immobilization. In young rats, metabolic pathways were primarily downregulated in response to immobilization (post-synaptic blockade of neuromuscular transmission). In old rats, on the other hand, dramatic immune and inflammatory responses were observed, i.e., an upregulation of specific related pathways such as “IL-17 signaling pathway”, along with a higher level of inflammatory factors and cytokine/chemokine in plasma.ConclusionsThe dramatically increased mortality in old ICU patients with COVID-19-associated hyperinflammation and cytokine storm need not only reflect the viral infection but may also be associated with the ventilator induced diaphragm dysfunction (VIDD) and hyperinflammatory responses induced by long-term CMV per se. Although mechanical ventilation is a life-saving intervention in COVID-19 ICU patients, CMV should be cautiously used especially in old age and other means of respiratory support may be considered, such as negative pressure ventilation.

SFRP2 Supersedes VEGF as an Age-related Driver of Angiogenesis in Melanoma, Affecting Response to Anti-VEGF Therapy in Older Patients.

Angiogenesis is thought to be critical for tumor metastasis. However, inhibiting angiogenesis using antibodies such as bevacizumab (Avastin), has had little impact on melanoma patient survival. We have demonstrated that both angiogenesis and metastasis are increased in older individuals, and therefore sought to investigate whether there was an age-related difference in response to bevacizumab, and if so, what the underlying mechanism could be. We analyzed data from the AVAST-M trial of 1,343 patients with melanoma treated with bevacizumab to determine whether there is an age-dependent response to bevacizumab. We also examined the age-dependent expression of VEGF and its cognate receptors in patients with melanoma, while using syngeneic melanoma animal models to target VEGF in young versus old mice. We also examined the age-related proangiogenic factor secreted frizzled-related protein 2 (sFRP2) and whether it could modulate response to anti-VEGF therapy. We show that older patients respond poorly to bevacizumab, whereas younger patients show improvement in both disease-free survival and overall survival. We find that targeting VEGF does not ablate angiogenesis in an aged mouse model, while sFRP2 promotes angiogenesis in vitro and in young mice. Targeting sFRP2 in aged mice successfully ablates angiogenesis, while the effects of targeting VEGF in young mice can be overcome by increasing sFRP2. VEGF is decreased during aging, thereby reducing response to bevacizumab. Despite the decrease in VEGF, angiogenesis is increased because of an increase in sFRP2 in the aged tumor microenvironment. These results stress the importance of considering age as a factor for designing targeted therapies.

Abstract 2749: Age-related cancer drug toxicity and efficacy, and immune modulation in C57BL6J syngeneic model

Abstract Cancer has a higher incidence in the elderly and immunotherapy is widely applied to this population. However, the majority of preclinical studies assessing drug toxicity and efficacy have been done in young healthy mice, which could lead to translational failure. The goals of this study were to establish tumor models in aged mice for a better representation of cancer patients, and to examine the effects of aging on tumor growth, toxicity and efficacy of cancer treatment, and immune cell populations in syngeneic models using C57BL/6J mice of different ages. Young (7 weeks), mid-aged (56-58 weeks) and aged (76-78 weeks) C57BL/6J female mice were used for this study. To evaluate the maximum tolerated dose, young and aged mice were dosed with the standard of care cancer drugs (docetaxel, cisplatin, and doxorubicin) and body weight was monitored three times a week until mice reached endpoint criteria. Syngeneic tumor models were established using three different mouse cancer cell lines, B16-F10 melanoma, MC38 colon adenocarcinoma, and E0771 breast cancer. Several different concentrations of cells were injected subcutaneously and tumor growth kinetics were evaluated three times weekly. For efficacy study, mice were randomly assigned to isotype control or Anti-PD1 (8 mg/kg) treatment groups, and were dosed intravenously twice weekly for 3 weeks. One week after the last dose, whole blood and tumor samples were collected for flow cytometry analysis for immune cell profiling on B cells, T cells, NK cells. Aged mice showed higher toxicity against docetaxel, cisplatin, and doxorubicin compared to their young counterparts. Age-related tumor growth kinetics varied based on tumor models. Aging did not affect tumor growth kinetics of B16-F10 tumors, while aged mice showed slowed growth of MC38 tumors and faster growth of E0771 tumors. Across all tumor models, aged mice lost body weight while young mice gained body weight over the course of tumor growth, suggesting potential cancer-related cachexia in aged mice. Comparisons of PD-1 response in the various age groups with different tumors showed that anti-PD1 treatment significantly slowed down tumor growth in mid-aged (58 weeks) mice with B16-F10 tumors, but not in young or aged mice. However, the same treatment showed significant suppression of tumor growth in all age groups with the MC38 tumors. This effect might be partly caused by changes in the immune cell infiltration profile with aging. In conclusion, we have established syngeneic tumor models using aged mice and found aged mice exhibit higher toxicity against drugs while the effect of aging on tumor growth kinetics varies depending on models. Differences in immune cell infiltration in the tumor might be an underlying event that causes age-related differences in response to anti-PD1 treatment. The integration of aging in cancer research could potentially bridge the gap between preclinical studies and clinical outcomes. Citation Format: Jiwon Yang, Andrew Schile, Mingshan Cheng, James Keck. Age-related cancer drug toxicity and efficacy, and immune modulation in C57BL6J syngeneic model [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2749.

Age-related differences in responses to hydrogen sulfide in the bladder of spontaneously hypertensive rats

Age-related differences in responses to hydrogen sulfide in the bladder of spontaneously hypertensive rats

Age-related differences in responses to hydrogen sulfide in the bladder of spontaneously hypertensive rats

Age-related differences in responses to hydrogen sulfide in the bladder of spontaneously hypertensive rats

Effects of Arginine and Inflammation on Protein Metabolism in Human Skeletal Muscle Cells (P01-034-19)

ObjectivesChronic inflammation is a hallmark of skeletal muscle (SkM) with advancing age and is thought to augment age-related SkM atrophy (sarcopenia). Arginine, a conditionally essential amino acid, is necessary for protein synthesis. Intriguingly, arginine has been identified as being important for attenuating nuclear factor kappa B (NF-κB) activity in non-muscle cells. Our objective was to determine the age-related effects of arginine and inflammation on markers of protein synthesis and breakdown in human myotubes. MethodsMuscle progenitor cells (MPCs) were obtained from SkM biopsy tissue of young (YNG, n = 5) and old (OLD, n = 5) women. MPCs were differentiated for 5 days (myotubes) followed by treatment with a pro-inflammatory cytokine, TNFα, for 6 h, 24 h, 48 h, or 96 h. Inflammatory activity and arginine uptake were determined using immunoblotting and radioactive isotopes. Protein synthesis was assessed with puromycin incorporation. MURF1 and MAFBX1 gene expression were used as indicators of proteolysis. ResultsPrior to TNFα treatment, OLD (vs. YNG) myotubes had greater arginine uptake (P = 0.02), but there were no age-related differences in basal p65 NF-κB activity, puromycin incorporation, or MAFBX1 and MURF1 expression (P > 0.05). Treatment with TNFα induced NF-κB activity in both YNG and OLD myotubes at 6 and 24 h of treatment (P < 0.0001), with no additional increase in activity from 24–96 h. CAT2, an arginine transporter, was transiently induced at 6 h of TNFα treatment (P < 0.01), with no age-related difference in response (P > 0.05). 96 h of TNFα increased arginine uptake in OLD (P < 0.05), but not YNG myotubes (P > 0.05). 6 h TNFα had no effect (P > 0.05), but 96 h of TNFα reduced puromycin incorporation in both YNG and OLD myotubes (P < 0.05). Compared to no treatment control, 96 h TNFα unexpectedly decreased MAFBX1 expression in both YNG and OLD myotubes (P < 0.001). Intriguingly, in the presence of TNFα, arginine increased MURF1 expression in YNG and OLD myotubes compared to no treatment control (P < 0.05). ConclusionsUnexpectedly, arginine amplified markers of proteolysis, and did not affect protein synthesis. Future studies will investigate regulatory transcription factors involved in protein breakdown and a crude marker of protein balance (e.g., myotube diameter). Funding SourcesPresident’s Council for Cornell Women.

The Effect of M-Cholinoreceptor Blockade on Functional Activity of Somatomotor, Cardiovascular and Respiratory Systems in Newborn Rats upon Activation of Cholinoreactive Structures

Activities of the somatomotor, cardiovascular and respiratory systems were investigated in conditions of impaired cholinergic regulation in rat pups aged 1 and 16 days. Acetylcholinesterase (AChE) inhibition by physostigmine (eserine), which leads to activate cholinoreactive structures, is accompanied by a unidirectional impairment of the cardiac sinus rhythm in newborn and, to a lesser extent, 16-day-old rats. Activation of cholinoreactive structures decreases the rate and regularity of breathing and also alters the pattern and parameters of motor activity. Physostigmine injection potentiates motor activity in 1-day-old and depresses it in 16-day-old rats. The blockade of muscarinic cholinoreceptors in rats of both age groups largely affects functional activity of the cardiovascular system, preventing severe cardiac arrhythmias caused by injection of the AChE inhibitor. It was shown that the formation of the definitive level of cholinergic regulation, including the maturation of the mechanisms underlying reciprocal interactions within the cholinergic system itself, is completed in the early period of rat postnatal ontogenesis. Age-related differences in responses of the somatomotor, cardiovascular and respiratory systems to changes in the level of activation of cholinoreactive structures are associated with these processes.

Age exacerbates microglial activation, oxidative stress, inflammatory and NOX2 gene expression, and delays functional recovery in a middle-aged rodent model of spinal cord injury

BackgroundSpinal cord injury (SCI) among people over age 40 has been steadily increasing since the 1980s and is associated with worsened outcome than injuries in young people. Age-related increases in reactive oxygen species (ROS) are suggested to lead to chronic inflammation. The NADPH oxidase 2 (NOX2) enzyme is expressed by microglia and is a primary source of ROS. This study aimed to determine the effect of age on inflammation, oxidative damage, NOX2 gene expression, and functional performance with and without SCI in young adult (3 months) and middle-aged (12 months) male rats.MethodsYoung adult and middle-aged rats were assessed in two groups—naïve and moderate contusion SCI. Functional recovery was determined by weekly assessment with the Basso, Beattie, and Breshnahan general motor score (analyzed two-way ANOVA) and footprint analysis (analyzed by Chi-square analysis). Tissue was analyzed for markers of oxidative damage (8-OHdG, Oxyblot, and 3-NT), microglial-related inflammation (Iba1), NOX2 component (p47PHOX, p22PHOX, and gp91PHOX), and inflammatory (CD86, CD206, TNFα, and NFκB) gene expression (all analyzed by unpaired Student’s t test).ResultsIn both naïve and injured aged rats, compared to young rats, tissue analysis revealed significant increases in 8-OHdG and Iba1, as well as inflammatory and NOX2 component gene expression. Further, injured aged rats showed greater lesion volume rostral and caudal to the injury epicenter. Finally, injured aged rats showed significantly reduced Basso–Beattie–Bresnahan (BBB) scores and stride length after SCI.ConclusionsThese results show that middle-aged rats demonstrate increased microglial activation, oxidative stress, and inflammatory gene expression, which may be related to elevated NOX2 expression, and contribute to worsened functional outcome following injury. These findings are essential to elucidating the mechanisms of age-related differences in response to SCI and developing age-appropriate therapeutics.

Age-Related Changes in Immunological and Physiological Responses Following Pulmonary Challenge.

This review examines the current status of knowledge of sepsis and pneumonia in the elderly population and how the dynamics of the pulmonary challenge affects outcome and consequences. Led by an unprecedented shift in demographics, where a larger proportion of the population will reach an older age, clinical and experimental research shows that aging is associated with certain pulmonary changes, but it is during infectious insult of the lungs, as in the case of pneumonia, that the age-related differences in responsiveness and endurance become obvious and lead to a worse outcome than in the younger population. This review points to the neutrophil, and the endothelium as important players in understanding age-associated changes in responsiveness to infectious challenge of the lung. It also addresses how the immunological set-point influences injury-repair phases, remote organ damage and how intake of drugs may alter the state of responsiveness in the users. Further, it points out the importance of considering age as a factor in inclusion criteria in clinical trials, in vitro/ex vivo experimental designs and overall interpretation of results.

Age-related differences in the response of the L5-S1 intervertebral disc to spinal traction

BackgroundLumbar traction is a common treatment for low back pain; however its mechanisms of action are poorly understood. It has been hypothesized that a key effect of lumbar traction is its capacity to influence fluid movement within the intervertebral disc (IVD). ObjectivesTo determine differences in the apparent diffusion coefficient (ADC) obtained with lumbar diffusion-weighted imaging (DWI) of the L5-S1 IVD before, and during, the application of lumbar traction. DesignCase series, repeated measures. MethodsA static traction load of ∼50% of body-weight was applied to the low back using a novel “MRI-safe” apparatus. DWI of the lumbar spine was performed prior to, and during the application of the traction load. ResultsParticipants were currently asymptomatic and included a young adult group (n = 18) and a middle-aged group (n = 15). The young adult group had a non-significant 2.2% increase in ADC (mean change = 0.03 × 10−3 mm2/s, SD = 0.24, 95% CI = −0.09, 0.15). The ADC for the middle-aged group significantly increased by 20% (mean change of 0.18 × 10−3 mm2/s, SD = 0.19; 95% CI = 0.07, 0.28; p = 0.003; effect size = 0.95). There was an inverse relationship between the ADC obtained before traction and the percent increase in ADC that was measured during traction. ConclusionStatic traction was associated with an increase in diffusion of water within the L5-S1 IVDs of middle-age individuals, but not in young adults, suggesting age-related differences in the diffusion response. Further study is needed to assess the relationship between these findings and the symptoms of back pain. Level of evidence4.

Age Differences in the Effects of Mortality Salience on the Correspondence Bias.

According to terror management theory, awareness of death affects diverse aspects of human thought and behavior. Studies have shown that older and younger adults differ in how they respond to reminders of their mortality. The present study investigated one hypothesized explanation for these findings: Age-related differences in the tendency to make correspondent inferences. The correspondence bias was assessed in younger and older samples after death-related, negative, or neutral primes. Younger adults displayed increased correspondent inferences following mortality primes, whereas older adults' inferences were not affected by the reminder of death. As in prior research, age differences were evident in control conditions; however, age differences were eliminated in the death condition. Results support the existence of age-related differences in responses to mortality, with only younger adults displaying increased reliance on simplistic information structuring after a death reminder.

EEG Oscillation Evidences of Enhanced Susceptibility to Emotional Stimuli during Adolescence.

Background: Our recent event-related potential (ERP) study showed that adolescents are more emotionally sensitive to negative events compared to adults, regardless of the valence strength of the events. The current work aimed to confirm this age-related difference in response to emotional stimuli of diverse intensities by examining Electroencephalography (EEG) oscillatory power in time-frequency analysis.Methods: Time-frequency analyses were performed on the EEG data recorded for highly negative (HN), moderately negative (MN) and Neutral pictures in 20 adolescents and 20 adults during a covert emotional task. The results showed a significant age by emotion interaction effect in the theta and beta oscillatory power during the 500–600 ms post stimulus.Results: Adolescents showed significantly less pronounced theta synchronization (ERS, 5.5–7.5 Hz) for HN stimuli, and larger beta desynchronization (ERD; 18–20 Hz) for both HN and MN stimuli, in comparison with neutral stimuli. By contrast, adults exhibited no significant emotion effects in theta and beta frequency bands. In addition, the analysis of the alpha spectral power (10.5–12 Hz; 850–950 ms) showed a main effect of emotion, while the emotion by age interaction was not significant. Irrespective of adolescents or adults, HN and MN stimuli elicited enhanced alpha suppression compared to Neutral stimuli, while the alpha power was similar across HN and MN conditions.Conclusions: These results confirmed prior findings that adolescents are more sensitive to emotionally negative stimuli compared to adults, regardless of emotion intensity, possibly due to the developing prefrontal control system during adolescence.