Age-related Changes In Response Research Articles

Age-related changes in responsiveness to non-invasive brain stimulation neuroplasticity paradigms: A systematic review with meta-analysis

ObjectivesWe aimed to summarise and critically appraise the available evidence for the effect of age on responsiveness to non-invasive brain stimulation (NBS) paradigms delivered to the primary motor cortex. MethodsFour databases (Medline, Embase, PsycINFO and Scopus) were searched from inception to February 7, 2023. Studies investigating age group comparisons and associations between age and neuroplasticity induction from NBS paradigms were included. Only studies delivering neuroplasticity paradigms to the primary motor cortex and responses measured via motor-evoked potentials (MEPs) in healthy adults were considered. Results39 studies, encompassing 40 experiments and eight NBS paradigms were included: paired associative stimulation (PAS; n = 12), repetitive transcranial magnetic stimulation (rTMS; n = 2), intermittent theta burst stimulation (iTBS; n = 8), continuous theta burst stimulation (cTBS; n = 7), transcranial direct and alternating current stimulation ((tDCS; n = 7; tACS; n = 2)), quadripulse stimulation (QPS; n = 1) and i-wave periodic transcranial magnetic stimulation (iTMS; n = 1). Pooled findings from PAS paradigms suggested older adults have reduced post-paradigm responses, although there was considerable heterogeneity. Mixed results were observed across all other NBS paradigms and post-paradigm timepoints. Conclusions/significanceWhilst age-dependent reduction in corticospinal excitability is possible, there is extensive inter- and intra-individual variability both within and between studies, making it difficult to draw meaningful conclusions from pooled analyses.

Dynamic spatiotemporal coordination of neural stem cell fate decisions occurs through local feedback in the adult vertebrate brain.

SummaryNeural stem cell (NSC) populations persist in the adult vertebrate brain over a lifetime, and their homeostasis is controlled at the population level through unknown mechanisms. Here, we combine dynamic imaging of entire NSC populations in their in vivo niche over several weeks with pharmacological manipulations, mathematical modeling, and spatial statistics and demonstrate that NSCs use spatiotemporally resolved local feedback signals to coordinate their decision to divide in adult zebrafish brains. These involve Notch-mediated short-range inhibition from transient neural progenitors and a dispersion effect from the dividing NSCs themselves exerted with a delay of 9–12 days. Simulations from a stochastic NSC lattice model capturing these interactions demonstrate that these signals are linked by lineage progression and control the spatiotemporal distribution of output neurons. These results highlight how local and temporally delayed interactions occurring between brain germinal cells generate self-propagating dynamics that maintain NSC population homeostasis and coordinate specific spatiotemporal correlations.

Children and adolescents’ neural response to emotional faces and voices: Age-related changes in common regions of activation

ABSTRACT The perception of facial and vocal emotional expressions engages overlapping regions of the brain. However, at a behavioral level, the ability to recognize the intended emotion in both types of nonverbal cues follows a divergent developmental trajectory throughout childhood and adolescence. The current study a) identified regions of common neural activation to facial and vocal stimuli in 8- to 19-year-old typically-developing adolescents, and b) examined age-related changes in blood-oxygen-level dependent (BOLD) response within these areas. Both modalities elicited activation in an overlapping network of subcortical regions (insula, thalamus, dorsal striatum), visual-motor association areas, prefrontal regions (inferior frontal cortex, dorsomedial prefrontal cortex), and the right superior temporal gyrus. Within these regions, increased age was associated with greater frontal activation to voices, but not faces. Results suggest that processing facial and vocal stimuli elicits activation in common areas of the brain in adolescents, but that age-related changes in response within these regions may vary by modality.

Age-related factors that affect B cell responses to vaccination in mice and humans.

Aging significantly changes the ability to respond to vaccinations and infections. In this review, we summarize published results on age-related changes in response to infection with the influenza virus and on the factors known to increase influenza risk infection leading to organ failure and death. We also summarize how aging affects the response to the influenza vaccine with a special focus on B cells, which have been shown to be less responsive in the elderly. We show the cellular and molecular mechanisms contributing to the dysfunctional immune response of the elderly to the vaccine against influenza. These include a defective interaction of helper T cells (CD4+) with B cells in germinal centers, changes in the microenvironment, and the generation of immune cells with a senescence-associated phenotype. Finally, we discuss the effects of aging on metabolic pathways and we show how metabolic complications associated with aging lead to immune dysfunction.

The Surface Proteome of Adult Neural Stem Cells in Zebrafish Unveils Long-Range Cell-Cell Connections and Age-Related Changes in Responsiveness to IGF

SummaryIn adult stem cell populations, recruitment into division is parsimonious and most cells maintain a quiescent state. How individual cells decide to enter the cell cycle and how they coordinate their activity remains an essential problem to be resolved. It is thus important to develop methods to elucidate the mechanisms of cell communication and recruitment into the cell cycle. We made use of the advantageous architecture of the adult zebrafish telencephalon to isolate the surface proteins of an intact neural stem cell (NSC) population. We identified the proteome of NSCs in young and old brains. The data revealed a group of proteins involved in filopodia, which we validated by a morphological analysis of single cells, showing apically located cellular extensions. We further identified an age-related decrease in insulin-like growth factor (IGF) receptors. Expressing IGF2b induced divisions in young brains but resulted in incomplete divisions in old brains, stressing the role of cell-intrinsic processes in stem cell behavior.

Age-related changes in ON and OFF responses to luminance increments and decrements.

Impulse response functions for an incremental luminous pulse (ON flash) or a decremental luminous pulse (OFF flash) were derived for twelve young (19-24 years old) and ten old (65-84 years old) observers. Thresholds were measured for two pulses separated by stimulus-onset-asynchronies from 13.3 to 186.7 ms. The pulses had a spatial Gaussian shape and were presented as increments or decrements on a 15 cd/m2 equal-energy white background, having the same chromaticity as the pulse. A spatial four-alternative forced-choice method was combined with a staircase procedure. Retinal illuminance was equated individually by heterochromatic flicker photometry and using a 2.3-mm exit pupil in a Maxwellian-view optical system to reduce the effects of age-related changes and individual variations in lens density and pupil size. Luminance ON- and OFF-impulse response functions calculated from the threshold data revealed significant age-related changes in the response amplitude of both first excitatory and first inhibitory phases. However, there were no significant changes in the time to the first peak or the second peak. These age-related changes in luminance varying ON- and OFF-impulse response functions (IRFs), reflecting putative properties of the magnocellular pathway, are discussed in relation to motion detection and the balance of ON and OFF pathways across the life span.

Effects of aging on prefrontal brain activation during challenging walking conditions

BackgroundDeficits in cognitive domains, in particular, those related to the prefrontal cortex, contribute to diminished walking performance in complex conditions in older age. Studies using functional near infra-red spectroscopy (fNIRS) reported inconsistent findings of brain activation age-related changes in response to increased task demands. We aimed to study the effects of aging on gait and prefrontal activation in complex walking tasks with internal and external task demands. MethodsTwenty-three healthy young adults (30.9±3.7yrs) and 20 healthy older adults (69.7±5.8yrs) participated in this study. Gait and prefrontal activation were assessed during three walking conditions: (1) usual walking, (2) dual tasking (internal task demands) and, (3) obstacle negotiation (external task demands). fNIRS measured changes in oxygenated hemoglobin concentrations in the prefrontal cortex. ResultsSeveral gait measures were worse in older compared to younger adults under all walking conditions (p<0.005). Even at the lowest level of challenge, older adults had significant increases in HbO2 levels during usual walking, relative to standing (p=0.006). Both groups showed increased activation during dual-task (p<0.002) and during obstacle negotiation (p<0.003). ConclusionsPrefrontal activation during walking is dependent on age and task properties and that older adults apparently rely more on cognitive resources even during usual walking task.

Impaired adrenergic agonist-dependent beige adipocyte induction in aged mice.

There are two types of thermogenic adipocytes expressing uncoupling protein (UCP)-1: the brown adipocyte activated by adrenergic stimulation and the beige adipocyte that appears within the white adipose tissue (WAT) in response to chronic adrenergic stimulation. This study examined age-related changes in responses of both types of adipocytes to adrenergic stimulation in mice. Aged (age 20 months) and young (4 months) mice were injected daily with either saline or β3-adrenergic receptor agonist CL316,243 (CL; 0.1 mg/kg, once a day) for 1 week. The body and WAT weight tended to be higher in aged mice. CL treatment increased UCP-1 protein amounts in both brown adipose tissue and inguinal WAT, suggesting activation of brown and beige adipocytes. However, induction of beige adipocytes was impaired in aged mice, whereas brown adipocyte activation was comparable to young mice. The number of platelet-derived growth factor receptor α-expressing progenitor cells, which were reported to differentiate into beige adipocytes, significantly decreased in inguinal WAT of aged mice compared with that of young mice. Inductive ability of beige adipocytes in WAT declines with aging in mice. It may be partly because of a decreased number of progenitor cells associated with aging.

Age-related Changes in Response of Highbush Blueberry Plants to Drip Irrigation

A study was conducted in the Fraser Valley of British Columbia, Canada, to determine the effects of drip configuration (one or two lines with emitters spaced every 0.3 or 0.45 m) and irrigation at moderate or heavy rates (5 or 10 L/plant) in a mature planting of ‘Duke’ highbush blueberry (Vaccinium corymbosum L.). Results were compared with those published previously from the first 4 years after planting. Although plant size increased with irrigation rate when the plants were younger, there was no added benefit of heavy irrigation on growth in the older plants. However, the plants became more sensitive to soil water deficits with age and, therefore, unlike when they were younger, had greater yields when more water was applied. Berry size and fruit firmness were little affected by irrigation in the older plants, but antioxidants, measured as oxygen radical absorbance capacity (ORAC), were higher with than without irrigation, suggesting that irrigation has the potential to improve the health benefits of blueberries. Growth, yield, and fruit quality were unaffected by drip configuration in any year. Overall, the results revealed that the response of highbush blueberry to drip irrigation changed over time and indicated that irrigation management should be adjusted as a planting matures.

Age increases anxiety and reactivity of the fear/anxiety circuit in Lewis rats

A growing body of data indicates that changes in emotional behavior occur with age. Young Lewis rats are known to display hypofunction of the HPA axis. With age the reactivity of this axis is thought to increase with a concomitant rise in anxiety. In the current study, we investigate how and if the pattern of neuronal activation (measured as c-Fos protein expression) in Lewis rat brains changes with age and in response to novel environments differing in aversiveness. We found that distinct parts of the fear/anxiety circuit (i.e., the amygdalar complex, hippocampus and hypothalamus) undergo diverse age-related changes in response to behavioral challenges. While in the hypothalamus an increase in responsivity to mild stressors was observed with age, no such effect was present in the hippocampus. The amygdalar complex (especially the medial and cortical nuclei) on the other hand exhibited an age-dependent decrease in neuronal activation to mild stressors. This was accompanied by a marked increase in anxiety not correlated with a decline in locomotor activity.

The Developmental Neuroscience of Moral Sensitivity

Though traditional accounts of moral development focus on the development of rational and deliberate thinking, recent work in developmental affective neuroscience suggests that moral cognition is tightly related to affective and emotional processing. Functional magnetic resonance imaging studies show age-related changes in response to empathy-eliciting stimuli, with a gradual shift from the monitoring of somatovisceral responses in young children mediated by the amygdala, insula and medial aspect of the orbitofrontal cortex, to the executive control and evaluation of emotion processing implemented by the ventromedial prefrontal cortex in older participants. These data indicate that the development of moral reasoning involves the increasing integration of empathic emotion-related somatovisceral responses with more complex social-reasoning abilities.

Anticonvulsant actions of deoxycorticosterone

Purpose: Adrenocorticotrophic hormone (ACTH) suppresses several types of childhood seizures, but it has many side effects. The mechanism of ACTH’s anticonvulsant actions is not known. ACTH, however, releases deoxycorticosterone (DOC) – as well as cortisol – from the adrenal cortex and it has been suggested that DOC may mediate, at least in part, ACTH’s anticonvulsant actions. The present study assessed DOC’s anticonvulsant actions in infant rats. Age-related changes in DOC’s anticonvulsant actions were also studied. Methods: DOC’s anticonvulsant actions were assessed against hippocampal-kindled, maximal pentylenetetrazol test (MMT) and maximal electroshock (MES) seizures in 15-day-old rats. Age-related changes in responsiveness to DOC were also assessed using the MMT model. Results: DOC suppressed generalized convulsions in all three of the seizure models. Focal spiking in the hippocampal-kindling model, however, was not fully suppressed, even at high doses. Ataxia increased proportionally with the dose, with the time of peak seizure suppression roughly correlating with the time of peak ataxia in all models. DOC was anticonvulsant in both infant and adult rats. ED50s, however, were much higher in adults. Young rats showed ataxia at the time of testing (15 min), whereas adult rats did not, although ataxia was seen at later times. Conclusions: DOC is a potent anticonvulsant against generalized seizures, particularly in infants. It deserves a clinical test against generalized seizures in infants.

Age-related endocrine dysfunction in nonhuman primates.

Peculiarities of functioning of some parts of the endocrine system (the pineal gland, pancreatic gland, hypothalamic-pituitary-adrenal axis, and hypothalamic-pituitary-testicular axis) in an aging nonhuman primate model (Papio hamadryas and Macaca mulatta) are described in this article. It has been established that basal activity of some endocrine functions (glucocorticoid, corticotropic, pancreatic, male estradiol producing) varies little with age. Other functions significantly decrease (DHEA/DHEAS-producing, pineal, testicular) or increase (male gonadotropic) with age. In contrast with basal activity, pronounced age-related changes in response to specific stimuli were detected in all endocrine functions. Old baboons and rhesus monkeys exhibited a delay of the normalization of the pituitary-testicular axis, adrenal cortex, and pancreatic gland function after their activation in response to specific stimuli, such as LHRH, CRH, ACTH, and glucose. Old monkeys also demonstrate decreased HPA axis sensitivity to glucocorticoid regulation by negative feedback and the HPT axis to inhibitory effect of prolonged administration of LHRH agonist. Age-related changes in reactions of endocrine functions in response to specific stimulating and inhibiting stimuli indicate impaired resiliency of these functions. Age-related endocrine changes perhaps play a pathophysiological role in age function disorders of hormonocompetent tissues and organs and age pathology.

Schizophrenia in the Elderly

The treatment of schizophrenia in older populations poses special challenges for patients, family members and clinicians. These include changes in manifestation of schizophrenic illness in later life, age-related changes in response to pharmacological treatments and psychosocial issues associated with older life status.

Age-related changes in adenylyl cyclase activity in rat aorta membranes

Blood vessels from aged animals and humans have impaired relaxation and cAMP production to β-adrenergic stimulation. Direct activators of adenylyl cyclase (AC) such as forskolin are not affected. We hypothesized that analogous findings would occur in membrane preparations. Aortic media membrane preparations from Fischer 344 rats of four age groups (6 weeks to 24 months) were studied. Basal AC activity increased significantly with age. Forskolin-stimulated activity compared to basal tended to be greater in the 6-week and 6-month preparations compared to the 12- and 24-month preparations. AC activity was assessed in the presence of the G protein activators (GTP, GppNHp, NaF). There was no age-related decrease in responsiveness. The receptor agonists isoproterenol ( β-adrenergic), and PGE-1 (prostaglandin), were studied. There was no significant age-related change in responsiveness over basal activity to either of these agonists. There was a slight, but significant increase in the isoproterenol responsiveness over GTP responsiveness in the 6-week-old animals which also approached significance in the 6-month-old animals, but was not seen in the 12- and 24-month-old animals. These data suggest that using a membrane system to assess age-related changes in β-adrenergic responsiveness in vascular smooth muscle does not retain the robust differences seen in whole vessels.

Age-related changes in response of brain stem vessels to opening of ATP-sensitive potassium channels.

This study was designed to determine regional differences and age-related changes in the contribution of ATP-sensitive potassium (KATP) channels to vasodilator responses in the brain stem circulation in vivo. Changes in diameter of the basilar artery (baseline diameter, 270 +/- 5 microns [mean +/- SEM]), its large branch (112 +/- 5 microns), and its small branch (49 +/- 2 microns) in response to KATP channel openers levcromakalim and Y-26763 were measured through a cranial window in anesthetized adult (4 to 6 months) and aged (24 to 26 months) Sprague-Dawley rats. Topical application of levcromakalim and Y-26763 produced concentration-dependent vasodilation that was similar among the three vessel groups in adult rats. In aged rats, dilator responses of the branches, but not of the basilar artery, to the KATP channel openers were smaller than those in adult rats (P < .05). Glibenclamide, a selective KATP channel blocker, almost abolished this vasodilation in both groups of rats. Vasodilator responses to sodium nitroprusside were preserved in aged rats. In adult rats, there is no regional heterogeneity in vasodilator response to KATP channel openers in the brain stem circulation in vivo. In aged rats, although KATP channels are also functional in the brain stem circulation, dilator response of the microvessels but not of the large arteries to direct activation of KATP channels is impaired.

Age-related effects of Platelet Activating Factor (PAF) in the isolated perfused rat heart

Platelet Activating Factor (PAF) is a phospholipid that has been implicated as an important mediator of anaphylactic cardiac dysfunction and involved in the toxic effects of the ischaemia-reperfusion process. In the elderly, these phenomena are thought to be exaggerated by the age-related changes in response to several chemical factors and myocardial ischaemia. We evaluated the effects of PAF (acetyl-o-alkyl-l-phosphatidylcholine) on left ventricular systolic (LVSP) and diastolic (LVDP) pressure, coronary flow rate (CFR) and heart rate (HR) in adult (6 months, AH) and senescent (24 months, SH) rat hearts. The perfusion of PAF (10 −8, 10 −7 and 10 −6 m) induced a concentration-related reduction of LVSP, CFR and HR and a linear increase in LVDP. Contractile modifications were more pronounced in senescent hearts: LVSP decreased ( P < 0.01) and LVDP increased with respect to younger animals ( P < 0.01 vs. AH). This negative inotropic effect was also present in electrically paced hearts. PAF produced conduction arrhythmias ranging from second-degree atrio-ventricular conduction block to cardiac standstill both in adult and senescent hearts; at a higher dose (10 −6 m), cardiac standstill appeared after 96.5 ± 15.3 s in adult hearts and after 45.5 ± 17.6 s in senescent hearts ( P < 0.01). Lyso-PAF did not modify while specific PAF antagonist compounds CV-3988 inhibited all electromechanical responses both in adult and senescent hearts. These data suggest that age influences the effect of PAF on contractile parameters, coronary flow and conduction arrhythmias by acting on receptors, whose function is unaffected by age.

Age-related changes in responses to autonomic mediators in isolated human atrial fibers

Age-related changes in responses to autonomic mediators in isolated human atrial fibers

Age-related changes in responses to nerve stimulation and catecholamines in isolated monkey cerebral arteries

Mechanical responses to transmural electrical stimulation, nicotine, norepinephrine, and isoproterenol were compared in cerebral artery strips obtained from Japanese monkeys of different ages (1 mo, 1 yr, 4-7 yr, and greater than 7 yr old). Transmural electrical stimulation produced a contraction in the baby and juvenile monkey arteries contracted with prostaglandin F2 alpha, whereas the older monkey arteries responded to the stimulation with a relaxation. The stimulation-induced contraction was abolished or reversed to a relaxation by phentolamine; the relaxation was not influenced by propranolol and atropine but was abolished by tetrodotoxin, as was the response of the mature monkey arteries. Contractions caused by norepinephrine were greater in baby cerebral arteries than in the older monkey arteries; however, the apparent median effective concentration values did not differ. Middle cerebral artery contractions were greater than those of basilar arteries. The norepinephrine-induced contraction was suppressed by prazosin but not influenced by yohimbine. Isoproterenol (up to 10(-6) M) produced a greater relaxation in the baby arteries than in the older monkey arteries. It is suggested that adrenergic nerves innervating immature monkey cerebral arteries contribute to the regulation of vascular tone predominantly over nonadrenergic, noncholinergic vasodilator nerves, whereas the vasodilator nerves play a major role in the mature monkey arteries. alpha 1-Adrenoceptor subtype appears to be mainly involved in the norepinephrine-induced contraction of baby monkey cerebral arteries, as it is in that of the adult monkey arteries.

Age-related changes in the motor response to environmental novelty in the rat

To examine age-related changes in responsiveness to environmental novelty, 3-, 12-, and 24-month-old male Fischer 344 rats were maintained on a restricted diet and exposed to a modified open field for 10 min on each of 10 consecutive days. On the first day of testing, animals of all groups showed equal amounts of rearing. While the 3-month animals continued to show approximately the same levels of rearing until the 8th day, by day 5, the older groups (12- and 24-month) had significantly reduced their rearing. Conversely, grooming was initially highest among the 24-month-old animals. While 3- and 12-month rats showed habituation of grooming, the oldest animals failed to habituate their grooming response by day 5. By day 10, there were no significant differences among the groups in either rearing or grooming. Although food was available in the center of the modified open field, there was little eating and there were no differences among groups. However, all animals did eat quickly when food was made available in their home cages. Thus, all animals displayed a profile of stress-related responses to open field exposure. Plasma corticosterone levels likewise were elevated in the modified open field. Some, but not all, components of this response profile habituated over teh 10 dyas of exposure Three-month-old animals responded to the novelty predominantly by rearing and 24-month animals predominately by grooming. This suggests that with aging, locomotor responses to stress are replaced by a more self-directed form of displacement activity.