Age-specific Response Research Articles

Age-specific functional response and predation rate of Amblyseius swirskii (Phytoseiidae) on two-spotted spider mite

The lifetime functional response and predation rate of Amblyseius swirskii Athias-Henriot on eggs of the two-spotted spider mite, Tetranychus urticae Koch were determined under laboratory conditions using cucumber leaf discs. Densities of 2, 4, 8, 16, 32, 64 and 128 prey were offered to 3, 4, 5, 6, 7, 12, 17, 22 and 27-day-old A. swirskii individuals. Based on the logistic regression, the functional response of twelve-day-old A. swirskii was type III, while the other ages showed type II. The Rogers model was used to estimate searching efficiency (a) and handling time (Th). The longest handling time (1.387±0.315 h) was observed in the protonymphal stage, while the shortest handling time and highest maximum attack rate (T/Th) were estimated at the age of seven-days (0.396±0.057 h and 60.67 prey/day, respectively). In the functional response experiments, results of the highest prey density used (128 eggs) showed that the highest number of prey consumed by A. swirskii individuals aged twelve and seventeen-days old (35.6 and 43.1 eggs, respectively). It is concluded that A. swirskii could be an efficient biological control agent of T. urticae at the middle-age of its life and at higher prey densities.

Functional mapping of seasonal transition in perennial plants.

Unlike annuals, all perennial plants undergo seasonal transitions during ontogeny. As an adaptive response to seasonal changes in climate, the seasonal pattern of growth is likely to be under genetic control, although its underlying genetic basis remains unknown. Here, we develop a computational model that can map specific quantitative trait loci (QTLs) responsible for seasonal transitions of growth in perennials. The model is founded on functional mapping, a statistical framework to map developmental dynamics, which is reformed to integrate a seasonally adjusted growth function. The new model is equipped with a capacity to characterize the genetic effects of QTLs on seasonal alternation at different ages and then to better elucidate the genetic architecture of development. The model is implemented with a series of testing procedures, including (i) how a QTL controls an overall ontogenetic growth curve, (ii) how the QTL determines seasonal trajectories of growth within years and (iii) how it determines the dynamic nature of age-specific season response. The model was validated through computer simulation. The extension of season adjustment to other types of biological curves is statistically straightforward, facilitating a wider variety of genetic studies into ontogenetic growth and development in perennial plants.

P358: Age-specific transcriptional response to stroke

P358: Age-specific transcriptional response to stroke

Reference Curve for the First-Year Growth Response to Growth Hormone Treatment in Prepubertal Children with Idiopathic Growth Hormone Deficiency: Validation of the KIGS First-Year Growth Response Curve Using the Belgian Register for the Study of Growth and Puberty Problems

Background: Comparing observed and expected growth after first-year growth hormone (GH) therapy is useful for identifying a poor growth response to GH. Aim: To generate a first-year, age-specific growth response reference curve for prepubertal Belgian children with idiopathic growth hormone deficiency (iGHD) treated with a standard weight-adjusted GH dose and to compare this national reference with the response references derived from KIGS. Subjects and Methods: First-year height data of 357 prepubertal children (240 males) with iGHD were analyzed. Smooth reference curves of first-year height velocity (HV) in relation to age were created. Differences with the KIGS targets were evaluated after z-score transformation. Results: The observed first-year HVs were log-normal distributed by age and decreased significantly with age (p < 0.001). No GH dose or gender effect was observed (p = 0.5). Distance to target height, severity of GHD and occurrence of multiple pituitary hormone deficiencies had a positive effect (p < 0.01) on the calculated HV SDS. When applying the KIGS targets for severe iGHD, mean HV SDS was close to zero (-0.09 ± 0.84). Conclusion: The developed age-specific growth response curves enable rapid identification of poor response to first-year GH treatment in prepubertal iGHD children. Our results validate the published growth targets derived from the KIGS database.

Fascicles from energy-storing tendons show an age-specific response to cyclic fatigue loading

Some tendons, such as the human Achilles and equine superficial digital flexor tendon (SDFT), act as energy stores, stretching and recoiling to increase efficiency during locomotion. Our previous observations of rotation in response to applied strain in SDFT fascicles suggest a helical structure, which may provide energy-storing tendons with a greater ability to extend and recoil efficiently. Despite this specialization, energy-storing tendons are prone to age-related tendinopathy. The aim of this study was to assess the effect of cyclic fatigue loading (FL) on the microstructural strain response of SDFT fascicles from young and old horses. The data demonstrate two independent age-related mechanisms of fatigue failure; in young horses, FL caused low levels of matrix damage and decreased rotation. This suggests that loading causes alterations to the helix substructure, which may reduce their ability to recoil and recover. By contrast, fascicles from old horses, in which the helix is already compromised, showed greater evidence of matrix damage and suffer increased fibre sliding after FL, which may partially explain the age-related increase in tendinopathy. Elucidation of helix structure and the precise alterations occurring owing to both ageing and FL will help to develop appropriate preventative and repair strategies for tendinopathy.

Development and implementation of a paediatric observation and response chart

Introduction: In mid 2011, a review of existing paediatric observation charts at a metropolitan health network revealed linear recording of vital signs, contributing to poor recognition of deterioration in children and potentially resulting in late escalation and delayed management of unwell paediatric patients. Objectives: To develop and implement age-specific paediatric observation and response charts to improve recognition and response to clinical deterioration in children. Methods: Using the principles of the National Consensus Statement, observation charts were developed which included graphing of each parameter, an escalation algorithm and the ability to modify criteria to tailor to the individual. The charts and escalation criteria were tailored for four age groups: under 3 months, 3–12 months, 1–4 years, and 5–12 years. Following education and provision of lanyard cards with escalation criteria, the paediatric observation and response charts were introduced in November 2011. Results: The paediatric observation and response charts have been in use for over 18 months. To date, there has been an improvement in recognition and response to clinical deterioration in children, with an increase in reporting of clinical incidents. The charts have also been found to support clinicians’ decision making and assist in empowering the nurse to escalate care when concerned. Conclusions: The introduction of paediatric observation and response charts with age-specific escalation criteria is contributing to early and improved recognition and response to clinical deterioration in children across our health network.

Age-specific transcriptional response to stroke

Increased age is a major risk factor for stroke incidence and post-ischemic mortality. To develop age-adjusted therapeutic interventions, a clear understanding of the complexity of age-related post-ischemic mechanisms is essential. Transient occlusion of the middle cerebral artery—a model that closely resembles human stroke—was used to induce cerebral infarction in mice of 4 different ages (2, 9, 15, 24 months). By using Illumina cDNA microarrays and quantitative PCR we detected a distinct age-dependent response to stroke involving 350 differentially expressed genes. Our analyses also identified 327 differentially expressed genes that responded to stroke in an age-independent manner. These genes are involved in different aspects of the inflammatory and immune response, oxidative stress, cell cycle activation and/or DNA repair, apoptosis, cytoskeleton reorganization and/or astrogliosis, synaptic plasticity and/or neurotransmission, and depressive disorders and/or dopamine-, serotonin-, GABA-signaling. In agreement with our earlier work, aged brains displayed an attenuated inflammatory and immune response (Sieber et al., 2011) and a reduced impairment of post-stroke synaptic plasticity. Our data also revealed a distinct age-related susceptibility for post-ischemic depression, the most common neuropsychiatric consequence of stroke, which has a major influence on functional outcome.

Neuromuscular interactions around the knee in children, adults and elderly.

Although injury and neuromuscular activation patterns may be common for all individuals, there are certain factors which differentiate neuromuscular activity responses between children, adults and elderly. The purpose of this study is to review recent evidence on age differences in neural activation and muscle balances around the knee when performing single joint movements. Particularly, current evidence indicates that there are some interesting similarities in the neuromuscular mechanisms by which children or the elderly differ compared with adults. Both children and elderly display a lower absolute muscle strength capacity than adults which cannot fully be explained by differences in muscle mass. Quadriceps activation failure is a common symptom of all knee injuries, irrespective of age but it is likely that its effect is more evident in children or adults. While one might expect that antagonist co-activation would differ between age categories, it appears that this is not the case. Although hamstring: quadriceps ratio levels are altered after knee injury, it is not clear whether this is an age specific response. Finally, evidence suggests that both children and the elderly display less stiffness of the quadriceps muscle-tendon unit than adults which affects their knee joint function.

Age-specific locomotor response to nicotine in yellow and mottled yellow Avy/a mice

BackgroundMost Agouti viable yellow (Avy) mice display constitutive expression of agouti protein, which acts as an inverse agonist at the melanocortin receptor 4 (Mc4r), resulting in adult-onset obesity as well as an altered sensitivity to some drugs of abuse. We investigated the influence of excessive agouti expression on open-field locomotor response to daily 0.5 mg/kg (-)-freebase nicotine injections in 27 early adolescent and 27 young adult male Avy/a and a/a mice, and assessed the effects of nicotine administration (0.5 mg/kg) followed by open-field testing on serum corticosterone levels in a separate group of 25 young adult male Avy/a and a/a mice.FindingsYoung adult Avy/a mice displayed pronounced nicotine-induced hypolocomotion (a 24% reduction in distance traveled) compared to their a/a littermates. Early adolescent Avy/a mice did not differ from their a/a littermates or saline-matched controls in locomotion following nicotine administration. Young adult Avy/a mice also displayed increased thigmotaxis (a 5% increase in time spent outside the center of the apparatus) on the first day of nicotine administration as compared to saline-matched controls, while a/a mice did not. An increase in serum corticosterone levels 20 minutes after nicotine injection in a separate group of young adult male mice (n = 25) was proportionally similar between Avy/a and a/a mice.ConclusionsOverall, the results suggest an age- and epigenotype- or genotype-specific response to nicotine administration in young adult male Avy/a mice. It appears the Avy/a locomotor and thigmotaxic responses to acute nicotine administration are not mediated solely by hypothalamic-pituitary-adrenal (HPA) axis stimulation.

Age-specific responses to elevated salinity in the coastal marsh plant black needlerush (Juncus roemerianus Scheele) as determined through polyphasic chlorophyll a fluorescence transients (OJIP)

This study employed polyphasic chlorophyll a fluorescence transients (OJIP), a non-invasive marker of environmental stress in plants, to evaluate salt tolerance in three different Juncus roemerianus age classifications (6-, 24-, and 60-months). Following exposure to elevated salts (30 psu), the younger plants sustained growth, which was comparable to freshwater controls. While older (60-month) plants receiving only freshwater also grew over the 8-week study, the older salt-treated plants did not increase in size. Similarly, there were significant declines in variable chlorophyll a fluorescence parameters (Fv/Fm and Fv/Fo), electron transport flux per reaction center (ETo/RC), and photosystem II performance index (PIABS) for 60-month J. roemerianus following salt treatment. These responses were not evident in the two younger salt-treated age classifications. Our results suggest that older J. roemerianus are less tolerant to rapid and sudden increases in salinity relative to younger plants and that this age-specific response may help explain observed discrepancies in salt tolerance in J. roemerianus.

Differential control of H-reflex amplitude in different weight-bearing conditions in young and elderly subjects

ObjectiveThis study measured the modulation of conditioned (femoral nerve, paired-stimuli) and unconditioned soleus H-reflexes in young and elderly subjects when changing weight-bearing (WB) requirements and body position. MethodsConditioned and unconditioned H-reflexes were examined in 14 elderly subjects and 11 young subjects during six different WB conditions: (1) lying supine with no WB, (2) supine position inclined by 30° with 50% WB, (3) standing with 50%, (4) 75%, (5) 100% and (6) 125% WB. ResultsThe elderly subjects had consistently higher background soleus EMG activity across the WB conditions compared to the young. Femoral nerve conditioning caused facilitation of the H-reflex that changed across WB conditions in the young subjects, but not in the elderly subjects. Finally, elderly subjects had less depression with paired-stimulation (PRD) across WB conditions, which was not observed in the young subjects. ConclusionsThe elderly may have more direct activation of motoneurons from descending pathways, coupled with less segmental spinal control of inhibitory interneurons, as evidenced by the increased background soleus activity, H/M-max ratios and the lack of modulatory control observed when conditioning the H-reflex. SignificanceThere was an age-specific response from descending and segmental pathways during conditions that involved either different WB requirements or changes in body position.

Age dependency of estrogen responsiveness in the uterus and adipose tissue of aromatase-knockout (ArKO) mice

Aging is often associated with weight gain caused by metabolic changes including an increase of body fat. In this study we assessed the impact of age on estrogen responsiveness in the uterus and adipose tissue (AT) in aromatase-knockout (ArKO) mice. ArKO mice at the age of three or twelve months respectively were treated s.c. with vehicle, E 2 (10 μg/kg BW/d) or genistein (15 mg/kg BW/d) for three days. In the ArKO mouse model we were able to demonstrate that estrogen treatment resulted in an age specific response pattern both on a physiological and molecular level. Assessment of basal gene expression levels revealed significant age dependent differences only for elevated Esr1 levels in the uterus and leptin levels in infrarenal fat as well as lower levels of Pparg in the gonadal fat tissue. Investigating age dependency of estrogen responsiveness we were able to show that the E 2 and genistein resulted in age related pattern of regulation of expression of Esr1 and Lep in infrarenal and gonadal AT as well as the uterine expression of Pgr, Ltf and Pparg. In conclusion, evidence is provided that aging has an impact on the effectiveness of estrogen regulated processes in uterus and AT of ArKO mice. It remains to be elucidated whether or not this is associated with weight gain caused by an increase in body fat mass.

Impact of Age on Chemotherapy Response in Head and Neck Cancer

Objective: 1) Determine if an association exists between age and overall survival (OS) and progression-free survival (PFS) in induction chemotherapy (IC) for head and neck cancer (HNC). 2) Compare age-specific response to 2 different chemotherapy regimen in HNC. Method: A total of 501 patients enrolled on TAX 324 study (1999 to 2003) were evaluated. Patients had nonmetastatic, unresectable stage III/IV HNC. A total of 255 patients received IC with docetaxel, cisplatin, 5FU (TPF), and 246 received cisplatin, 5 fluorouracil (PF). The cohort was split into 2 groups; 55 years. Results: Fisher exact test and general linear model approach compared clinical and demographic characteristics between treatment arms. Kaplan-Meir method estimated OS and PFS. Stepwise Cox regression modeled OS and PFS functions. A total of 249 patients were 55 years, 127 were assigned to TPF arm and 125 to PF arm, Total failures reached statistical significance between the 2 arms; there were 50 total failures in the TPF arm and 58 in the PF arm (0.65, 0.42-0.98; 0.04). Conclusion: Our study contradicts the small amount of published evidence on age-specific responses to chemotherapy regimen in breast, prostate, and lung cancer. It is the first study of its kind evaluating the role of age in overall survival in chemotherapy in HNC.

Deleterious Effects of Plasminogen Activators in Neonatal Cerebral Hypoxia-Ischemia

The immature brains of newborns often respond differently from the brains of adults when exposed to similar insults. Previous studies have indicated that although hypoxia-ischemia (HI) induces persistent thrombosis in adult brains, it only modestly impairs blood perfusion in newborn brains. Here, we used the Vannucci model of HI encephalopathy to study age-related responses to cerebral HI in rat pups. We found that HI triggered fibrin deposition and impaired blood perfusion in both neonatal and adult brains. However, these effects were only transient in neonatal brains (<4 hours) and were accompanied by acute induction of both tissue-type and urinary-type plasminogen activators (tPA and uPA), which was not observed in adult brains subjected to the same insult. Interestingly, activation of the plasminogen system persisted up to 24 hours in neonatal brains, long after the clearance of fibrin-rich thrombi. Furthermore, astrocytes and macrophages outside blood vessels expressed tPA after HI, suggesting the possibility of tPA/plasmin-mediated cytotoxicity. Consistent with this hypothesis, injection of alpha2-antiplasmin into cerebral ventricles markedly ameliorated HI-induced damage to neurofilaments and white matter oligodendrocytes, providing a dose-response reduction of brain injury after 7 days of recovery. Conversely, ventricular injection of tPA increased HI-induced brain damage. Together, these results suggest that tPA/plasmin induction, which may contribute to acute fibrinolysis, is a critical component of extravascular proteolytic damage in immature brains, representing a new therapeutic target for the treatment of HI encephalopathy.

Renal cell carcinoma in young compared to older patients: Comparison of clinicopathological risk factors and survival

Renal cell carcinoma (RCC) is primarily a disease of the elderly, most patients being diagnosed in their mid-60s. However, a significant number of patients are diagnosed at a younger age. The true effect of age at diagnosis on survival has been debated, tumor stage and grade being the strongest prognostic factors of survival. The aim of this nationwide study was to study the significance of young age at diagnosis as a prognostic factor in RCC. This retrospective study included all living patients with histologically verified RCC in Iceland diagnosed between 1971 and 2000 (n = 629). Different clinicopathological factors of patients diagnosed aged < 50 years (n = 99) were compared to those of patients diagnosed aged > or = 50 years (n = 530). Disease-specific survival was compared and multivariate analysis was used to evaluate prognostic variables. Clinical presentation, TNM stage, grade, tumor size and histological subtypes were comparable between the two groups. Prognostic factors were the same in both groups, most of them having a stronger prognostic value in younger patients. Both 5- and 10-year disease-specific survival was significantly higher in the younger group (66.4% vs 54.5% at 5 years). The clinicopathological profiles are comparable in RCC patients aged < and > or = 50 years. The reason for the more favorable survival of younger patients is not known. Further studies are needed, including studies on possible differences in age-specific host-tumor response.

Age-specific response of the grass Puccinellia distans to the presence of a fungal endophyte

Asexual fungal endophytes, which do not produce reproductive structures, spread in host populations only vertically via the propagules of their hosts. With such a close relationship between the fitness of the asexual endophyte and that of the host, the relationship is traditionally thought to be mutualistic. Here we present data showing that the positive effect of asexual endophytes may concern only a short period of the host's life and that its lifetime reproductive success may be reduced. We followed 180 individuals of a perennial grass, Puccinellia distans, for the first 3 years of their growth both in the field and in a common garden experiment. In the first 2 years, infected individuals produced more generative shoots with longer inflorescences. Three-year-old individuals produced significantly fewer generative shoots with shorter inflorescences when infected with the fungus Epichloë typhina. Moreover, the dry mass of above- and belowground parts after three seasons was significantly lower in infected individuals. We suggest that if the endophyte retains control over plant reproduction and if shorter generation time is more crucial for the fungus than for the perennial host, then the fungus should stimulate plant reproduction early in life even though infection incurs a future cost. This reasoning suggests that discovering an endophyte's beneficial effect on its perennial host in one season provides insufficient grounds for concluding that a mutualistic relationship exists.

259 RBM3 Expression in Neonates with Pontosubicular Neuron Necrosis

Objective: Pontosubicular neuron necrosis (PSN) represents an age-specific response to severe hypoxic-ischemic injury (HII) occurring in human neonates but not in older children or adults. Histologically, PSN is characterised by acute neuronal death in the pontine nuclei and the hippocampal subiculum bearing the hallmarks of apoptosis. The expression of Rbm3, a glycine-rich RNA-binding protein, is enhanced under hypoxic conditions and independent of HIF (hypoxia inducible factor). It is well known, that proteins which are dependant on HIF, e.g. Erythropoetin play an important role in HII. This study aims to determine whether the HIF-independent activation of Rbm3 is also a significant factor in the pathogenesis of PSN. Methods: We have investigated the expression of Rbm3 in human autopsy material consisting of 12 PSN cases and 10 age-matched controls without PSN. Immunohistochemistry and double labeling for Rbm3 and the astrocyte marker glial fibrillary acid protein (GFAP), the microglia/macrophage specific marker KiM1P and the neuronal marker NeuN was performed on formalin-fixed, paraffin-embedded brain specimens.Results: In PSN cases and controls, mainly neuronal cells expressed Rbm3. The number of immunopositive cells was significantly increased (p=0.001) in PSN cases. Predominantly degenerating cells with signs of later apoptotic stages showed Rbm3 expression. In earlier stages of apoptosis immunopositivity for Rbm3 was increased compared to contols, but less prominent.Conclusion: In addition to HIF-dependant proteins, the induction of the HIF-independent protein RMB3 is observed in response to human hypoxic-ischemic injury.

Developmentally Regulated Intestinal Expression of IFN-γ and Its Target Genes and the Age-Specific Response to Enteric Salmonella Infection

Young infants are highly susceptible to systemic dissemination of enteric pathogens such as Salmonella typhimurium when compared with older individuals. The mechanisms underlying this differential susceptibility have not been defined clearly. To better understand this phenomenon, we examined the responses of adult mice and preweaned pups to oral infection by S. typhimurium. We found clear age-specific differences, namely, an attenuated intestinal inflammatory response and a higher systemic bacterial burden in the pups compared with the adults. To elucidate the molecular basis for these differences, we obtained a microarray-based profile of gene expression in the small intestines of uninfected adult and preweaned animals. The results indicated a striking age-dependent increase in the intestinal expression of a number of IFN-gamma-regulated genes involved in antimicrobial defense. This finding was confirmed by real-time quantitative PCR, which also demonstrated an age-dependent increase in intestinal expression of IFN-gamma. The developmental up-regulation of the IFN-gamma-regulated genes was dependent on both IFN-gamma and a normal commensal microflora, as indicated by experiments in IFN-gamma-knockout mice and germfree mice, respectively. However, the increase in expression of IFN-gamma itself was independent of the commensal flora. The functional importance of IFN-gamma in the immunological maturation of the intestine was confirmed by the observation that the response of adult IFN-gamma-knockout animals to S. typhimurium infection resembled that of the wild-type pups. Our findings thus reveal a novel role for IFN-gamma in the developmental regulation of antimicrobial responses in the intestine.

Intraspecific differences in thermal tolerance of the diamondback watersnake ( Nerodia rhombifer): effects of ontogeny, latitude, and sex

Ontogenetic shifts in microhabitat use are widespread among taxa and can result in drastic shifts in thermal habitat among age classes. Likewise, geographic variation in climate along latitudinal gradients can cause differences in thermal environments among populations of a species. Using a common garden design, we examined four populations of a single species of semi-aquatic snake, Nerodia rhombifer, to determine whether ontogenetic shifts in habitat use (and/or body size) and latitudinal differences in ambient temperature have resulted in evolutionary changes in thermal tolerance. We found ontogenetic differences in thermal tolerance for all populations, with neonates tolerating temperatures 2 °C higher than adults, a pattern that is consistent with ontogenetic shifts in body size and microhabitat use in this species. There were differences in thermal tolerance among latitudes in neonates, suggesting genetic differences among populations, but adults showed no latitudinal differences. In combination, the increased thermal tolerance of neonates and the age-specific response to latitude suggest individuals may be most sensitive to selection on thermal tolerance as neonates. Although latitudinal differences exist in neonates, their tolerances were not ranked according to latitude, suggesting the effects of some other local factor (e.g., microclimate) may be important. Lastly, among neonates, females tolerate higher temperatures than males.

Age-specific immune response to HspA in Helicobacter pylori-positive persons in Mexico.

The immune response to heat shock protein A (HspA) in Helicobacter pylori-positive adults increases with age in developed countries. This response has not been studied with children or in developing countries (G. I. Pérez-Pérez, J. M. Thiberge, A. Labigne, and M. J. Blaser, J. Infect. Dis. 174:1046-1050, 1996). As determined by using a specific enzyme-linked immunosorbent assay, HspA seropositivity among 592 individuals in Mexico was <10% in children and increased to >40% in adults.