Effects Of Healthy Aging Research Articles

The Regulatory Status Adopted by Lymph Node Dendritic Cells and T Cells During Healthy Aging Is Maintained During Cancer and May Contribute to Reduced Responses to Immunotherapy.

Aging is associated with an increased incidence of cancer. One contributing factor could be modulation of immune cells responsible for anti-tumor responses, such as dendritic cells (DCs) and T cells. These immunological changes may also impact the efficacy of cancer immunotherapies in the elderly. The effects of healthy aging on DCs and T cells, and their impact on anti-mesothelioma immune responses, had not been reported. This study examined DCs and T cells in young (2–5 months; equivalent to 16–26 human years) and elderly (20–24 months; equivalent to 60–70 human years) healthy and mesothelioma-bearing C57BL/6J mice. During healthy aging, elderly lymph nodes adopted a regulatory profile, characterized by: (i) increased plasmacytoid DCs, (ii) increased expression of the adenosine-producing enzyme CD73 on CD11c+ cells, and (iii) increased expression of multiple regulatory markers (including CD73, the adenosine A2B receptor, CTLA-4, PD-1, ICOS, LAG-3, and IL-10) on CD8+ and CD4+ T cells, compared to lymph nodes from young mice. Although mesotheliomas grew faster in elderly mice, the increased regulatory status observed in healthy elderly lymph node DCs and T cells was not further exacerbated. However, elderly tumor-bearing mice demonstrated reduced MHC-I, MHC-II and CD80 on CD11c+ cells, and decreased IFN-γ by CD8+ and CD4+ T cells within tumors, compared to young counterparts, implying loss of function. An agonist CD40 antibody based immunotherapy was less efficient at promoting tumor regression in elderly mice, which may be due to: (i) failure of elderly CD8+ T cells to up-regulate perforin, and (ii) increased expression of multiple regulatory markers on CD11c+ cells and T cells in elderly tumor-draining lymph nodes (including CD73, PD-1, ICOS, LAG-3, and TGF-β). Our findings suggest that checkpoint blockade may improve responses to immunotherapy in elderly hosts with mesothelioma, and warrants further investigation.

Dimensional Complexity of the Resting Brain in Healthy Aging, Using a Normalized MPSE.

Spontaneous fluctuations of resting-state functional connectivity have been studied in many ways, but grasping the complexity of brain activity has been difficult. Dimensional complexity measures, which are based on Eigenvalue (EV) spectrum analyses (e.g., Ω entropy) have been successfully applied to EEG data, but have not been fully evaluated on functional MRI recordings, because only through the recent introduction of fast multiband fMRI sequences, feasable temporal resolutions are reached. Combining the Eigenspectrum normalization of Ω entropy and the scalable architecture of the so called Multivariate Principal Subspace Entropy (MPSE) leads to a new complexity measure, namely normalized MPSE (nMPSE). It allows functional brain complexity analyses at varying levels of EV energy, independent from global shifts in data variance. Especially the restriction of the EV spectrum to the first dimensions, carrying the most prominent data variance, can act as a filter to reveal the most discriminant factors of dependent variables. Here we look at the effects of healthy aging on the dimensional complexity of brain activity. We employ a large open access dataset, providing a great number of high quality fast multiband recordings. Using nMPSE on whole brain, regional, network and searchlight approaches, we were able to find many age related changes, i.e., in sensorimotoric and right inferior frontal brain regions. Our results implicate that research on dimensional complexity of functional MRI recordings promises to be a unique resource for understanding brain function and for the extraction of biomarkers.

Expectation of movement generates contrasting changes in multifinger synergies in young and older adults.

Anticipatory synergy adjustment (ASA) is a feed-forward control mechanism that describes a continuous decrease in the stability of the current motor state beginning about 150ms prior to a state transition. Recently, we described an associated phenomenon in which the system stability was reduced solely in response to a cue that generates an expectation of a state change, independent of whether the state change actually occurs. Both phenomena are of the same kind (stability reduction), but evoked by distinct antecedent conditions. Since, logically, cuing for movement must occur before the initiation of that movement, we named this new phenomenon 'Stage-1 ASA' and rechristened the well-established version 'Stage-2 ASA'. Here, we used a four-finger, isometric force production task to explore (1) the effect of healthy aging on Stage-1 ASA, and (2) if Stage-1 ASA resulted in a more rapid state change. Young and older adult participants produced 10% of their maximal force when they did not expect to produce any change in the force, and when they expected to change their force in an unknown direction and at an unknown time. In the latter condition, the 10% constant-force phase was followed by a choice reaction time task, in which the participants rapidly changed their force to follow a moving target presented on a computer monitor. Both young and older adults displayed equivalent amount of Stage-1 ASA. This was driven by a 42% reduction in finger-force variability in young adults. In contrast, it was driven by a 38% increase in finger-force variability in older adults. We speculate that the reduction in finger force variability assists the young adults in rapid state changes via two mechanisms: (1) the finger forces occupy a restricted set of states that are optimal for quick state transitions, and (2) lower variability during steady state translates into lower self-motion during state transition. Self-motion is the covariation between finger forces that fails to change the total force. The older adults are unable to adopt this strategy, and the increase in finger-force variability arises from (1) the adoption of an alternative strategy of destabilizing the attractor associated with the current state to facilitate state transitions and (2) the inability to coordinate multiple finger forces. Finally, older adults displayed longer reaction times than young adults, but a clear relation between Stage-1 ASA and consequent behavioral benefit in terms of reduced reaction time remained elusive.

Effect of healthy aging and sex on middle cerebral artery blood velocity dynamics during moderate-intensity exercise.

Blood velocity measured in the middle cerebral artery (MCAV) increases with finite kinetics during moderate-intensity exercise, and the amplitude and dynamics of the response provide invaluable insights into the controlling mechanisms. The MCAV response after exercise onset is well fit to an exponential model in young individuals but remains to be characterized in their older counterparts. The responsiveness of vasomotor control degrades with advancing age, especially in skeletal muscle. We tested the hypothesis that older subjects would evince a slower and reduced MCAV response to exercise. Twenty-nine healthy young (25 ± 1 yr old) and older (69 ± 1 yr old) adults each performed a rapid transition from rest to moderate-intensity exercise on a recumbent stepper. Resting MCAV was lower in older than young subjects (47 ± 2 vs. 64 ± 3 cm/s, P < 0.001), and amplitude from rest to steady-state exercise was lower in older than young subjects (12 ± 2 vs. 18 ± 3 cm/s, P = 0.04), even after subjects were matched for work rate. As hypothesized, the time constant was significantly longer (slower) in the older than young subjects (51 ± 10 vs. 31 ± 4 s, P = 0.03), driven primarily by older women. Neither age-related differences in fitness, end-tidal CO2, nor blood pressure could account for this effect. Thus, MCAV kinetic analyses revealed a marked impairment in the cerebrovascular response to exercise in older individuals. Kinetic analysis offers a novel approach to evaluate the efficacy of therapeutic interventions for improving cerebrovascular function in elderly and patient populations. NEW & NOTEWORTHY Understanding the dynamic cerebrovascular response to exercise has provided insights into sex-related cerebrovascular control mechanisms throughout the aging process. We report novel differences in the kinetics response of cerebrovascular blood velocity after the onset of moderate-intensity exercise. The exponential increase in brain blood flow from rest to exercise revealed that 1) the kinetics profile of the older group was blunted compared with their young counterparts and 2) the older women demonstrated a slowed response.

The Edinburgh Social Cognition Test (ESCoT): Examining the effects of age on a new measure of theory of mind and social norm understanding.

Current measures of social cognition have shown inconsistent findings regarding the effects of healthy aging. Moreover, no tests are currently available that allow clinicians and researchers to examine cognitive and affective theory of mind (ToM) and understanding of social norms within the same test. To address these limitations, we present the Edinburgh Social Cognition Test (ESCoT) which assesses cognitive and affective ToM and inter- and intrapersonal understanding of social norms. We examined the effects of age, measures of intelligence and the Broader Autism Phenotype (BAP) on the ESCoT and established tests of social cognition. Additionally, we investigated the convergent validity of the ESCoT based on traditional social cognition measures. The ESCoT was administered alongside Reading the Mind in Films (RMF), Reading the Mind in Eyes (RME), Judgement of Preference and Social Norm Questionnaire to 91 participants (30 aged 18–35 years, 30 aged 45–60 years and 31 aged 65–85 years). Poorer performance on the cognitive and affective ToM ESCoT subtests were predicted by increasing age. The affective ToM ESCoT subtest and RMF were predicted by gender, where being female predicted better performance. Unlike the ESCoT, better performance on the RMF was predicted by higher verbal comprehension and perceptual reasoning abilities, while better performance on the RME was predicted by higher verbal comprehension scores. Lower scores on inter-and intrapersonal understanding of social norms were both predicted by the presence of more autism-like traits while poorer interpersonal understanding of social norms performance was predicted by increasing age. These findings show that the ESCoT is a useful measure of social cognition and, unlike established tests of social cognition, performance is not predicted by measures of verbal comprehension and perceptual reasoning. This is particularly valuable to obtain an accurate assessment of the influence of age on our social cognitive abilities.

Dual regression physiological modeling of resting-state EPI power spectra: Effects of healthy aging

Aging and disease-related changes in the arteriovasculature have been linked to elevated levels of cardiac cycle-induced pulsatility in the cerebral microcirculation. Functional magnetic resonance imaging (fMRI), acquired fast enough to unalias the cardiac frequency contributions, can be used to study these physiological signals in the brain. Here, we propose an iterative dual regression analysis in the frequency domain to model single voxel power spectra of echo planar imaging (EPI) data using external recordings of the cardiac and respiratory cycles as input. We further show that a data-driven variant, without external physiological traces, produces comparable results. We use this framework to map and quantify cardiac and respiratory contributions in healthy aging. We found a significant increase in the spatial extent of cardiac modulated white matter voxels with age, whereas the overall strength of cardiac-related EPI power did not show an age effect.

The Effect of Deep Brain Stimulation Therapy on Fear-Related Capture of Attention in Parkinson's Disease and Essential Tremor: A Comparison to Healthy Individuals.

In addition to motor symptoms, Parkinson’s disease (PD) involves significant non-motor sequelae, including disruptions in cognitive and emotional processing. Fear recognition appears to be affected both by the course of the disease and by a common interventional therapy, deep brain stimulation of the subthalamic nucleus (STN-DBS). Here, we examined if these effects extend to other aspects of emotional processing, such as attentional capture by negative emotional stimuli. Performance on an emotional attentional blink (EAB) paradigm, a common paradigm used to study emotional capture of attention, was examined in a cohort of individuals with PD, both on and off STN-DBS therapy (n=20). To contrast effects of healthy aging and other movement disorder and DBS targets, we also examined performance in a healthy elderly (n=20) and young (n=18) sample on the same task, and a sample diagnosed with Essential Tremor (ET) undergoing therapeutic deep brain stimulation of the ventral-intermediate nucleus (VIM-DBS, n=18). All four groups showed a robust attentional capture of emotional stimuli, irrespective of aging processes, movement disorder diagnosis, or stimulation. PD patients on average had overall worse performance, but this decrement in performance was not related to the emotional capture of attention. PD patients exhibited a robust EAB, indicating that the ability of emotion to direct attention remains intact in PD. Congruent with other recent data, these findings suggest that fear recognition deficits in PD may instead reflect a highly specific problem in recognition, rather than a general deficit in emotional processing of fearful stimuli.

Effects of Healthy Aging and Mild Cognitive Impairment on a Real-Life Decision-Making Task.

In this study, we investigated the effects of age and of mild cognitive impairment (MCI) on decision making under risk by adopting a task representing real-life health-related situations and involving complex numerical information. Moreover, we assessed the relationship of real-life decision making to other cognitive functions such as number processing, executive functions, language, memory, and attention. For this reason, we compared the performance of 19 healthy, relatively younger adults with that of 18 healthy older adults and the performance of the 18 healthy older adults with that of 17 patients with MCI. Results indicated difficulties in real-life decision making for the healthy older adults compared with the healthy, relatively younger adults. Difficulties of patients with MCI relative to the healthy older adults arose in particular in difficult items requiring processing of frequencies and fractions. Significant effects of age and of MCI in processing frequencies were also evident in a ratio number comparison task. Decision-making performance of healthy participants and of the patient group correlated significantly with number processing. There was a further significant correlation with executive functions for the healthy participants and with reading comprehension for the patients. Our results suggest that healthy older individuals and patients with MCI make less advantageous decisions when the information is complex and high demands are put on executive functions and numerical abilities. Moreover, we show that executive functions and numerical abilities are not only essential in laboratory gambling tasks but also in more realistic and ecological decision situations within the health context.

Compliance instead of flexibility? On age-related differences in cognitive control during visual search

The effect of healthy aging on cognitive control of irrelevant visual information was investigated by using event-related potentials. Participants performed a spatial cuing task where an irrelevant color cue that was either contingent (color search) or noncontingent (shape search) on the attentional set was presented before a target with different stimulus-onset asynchronies. In the contingent condition, attentional capture appeared independent of age and persisted over the stimulus-onset asynchronies but was markedly pronounced for elderly people. Accordingly, event-related potential analyses revealed that both older and younger adults initially selected the irrelevant cue when it was contingent on the attentional set and transferred spatial cue information into working memory. However, only younger adults revealed inhibitory mechanisms to compensate for attentional capture. It is proposed that this age-related lack of reactive inhibition leads to stickiness in visual processing whenever information is contingent on the attentional set, unveiling older adults' “Achilles' heel” in cognitive control.

Research of short-term heart rate variability during sleep based on limited penetrable horizontal visibility graph

Heart rate is one of the most easily accessed human physiological data. In recent years, the analysis of sleep function based on heart rate variability has become a new popular feature of wearable devices used for daily health management. Consequently, it is needed to explore various types of short-term characteristic parameters which can be applied to the heartbeat interval time series within the standard sleep staging time window (about 30 s). Utilizing the recently reported limited penetrable horizontal visibility graph (LPHVG) algorithm, together with a weighted limited penetrable horizontal visibility graph (WLPHVG) algorithm proposed in this paper, the short-term heartbeat interval time series in different sleep stages are mapped to networks respectively. Then, 6 characteristic parameters, including the average clustering coefficient C, the characteristic path length L, the clustering coefficient entropy Ec, the distance distribution entropy Ed, the weighted clustering coefficient entropy ECw and the weight distribution entropy Ew are calculated and analyzed. The results show that the values of these characteristic parameters are significantly different in the states of wakefulness, light sleep, deep sleep and rapid eye movement, especially in the case of the limited penetrable distance Lp=1, indicating the effectiveness of LPHVG and WLPHVG algorithm in sleep staging based on short-term heartbeat interval time series. In addition, a preliminary comparison between proposed algorithm and the basic visibility graph (VG) algorithm shows that in this case, the LPHVG and WLPHVG algorithm are superior to the basic VG algorithm both in performance and in calculation speed. Meanwhile, based on the LPHVG and WLPHVG algorithm, the values of network parameters (the clustering coefficient entropy Ec and the weighted clustering coefficient entropy ECw) are calculated from heartbeat interval time series of healthy young and elder subjects in different sleep stages, to further study the aging effect on and sleep regulation over cardiac dynamics. It is found that despite an overall level difference between the values of Ec and ECw in young and elder groups, the stratification patterns across different sleep stages almost do not break down with advanced age, suggesting that the effect of sleep regulation on cardiac dynamics is significantly stronger than the effect of healthy aging. In addition, compared with the clustering coefficient entropy Ec based on LPHVG algorithm, the weighted clustering coefficient entropy ECw based on WLPHVG algorithm shows higher sensitivity to discriminating subtle differences in cardiac dynamics among different sleep states. Overall, it is shown that with the simple mapping criteria and low computational complexity, the proposed method could be used as a new auxiliary tool for sleep studies based on heart rate variability, and the corresponding network parameters could be used in wearable device as new auxiliary parameters for sleep staging.

The aging brain and changes in GABA concentrations

The aging brain and changes in GABA concentrations

The effects of healthy aging, amnestic mild cognitive impairment, and Alzheimer's disease on recollection, familiarity and false recognition, estimated by an associative process-dissociation recognition procedure

Given the uneven experimental results in the literature regarding whether or not familiarity declines with healthy aging and cognitive impairment, we compare four samples (healthy young people, healthy older people, older people with amnestic mild cognitive impairment – aMCI –, and older people with Alzheimer's disease – AD –) on an associative recognition task, which, following the logic of the process-dissociation procedure, allowed us to obtain corrected estimates of recollection, familiarity and false recognition. The results show that familiarity does not decline with healthy aging, but it does with cognitive impairment, whereas false recognition increases with healthy aging, but declines significantly with cognitive impairment. These results support the idea that the deficits detected in recollection, familiarity, or false recognition in older people could be used as early prodromal markers of cognitive impairment.

Adult Age Differences in Eye Movements During Reading: The Evidence From Chinese.

ObjectivesSubstantial evidence indicates that older readers of alphabetic languages (e.g., English and German) compensate for age-related reading difficulty by employing a more risky reading strategy in which words are skipped more frequently. The effects of healthy aging on reading behavior for nonalphabetic languages, like Chinese, are largely unknown, although this would reveal the extent to which age-related changes in reading strategy are universal. Accordingly, the present research used measures of eye movements to investigate adult age differences in Chinese reading.MethodThe eye movements of young (18–30 years) and older (60+ years) Chinese readers were recorded.ResultsThe older adults exhibited typical patterns of age-related reading difficulty. But rather than employing a more risky reading strategy compared with the younger readers, the older adults read more carefully by skipping words infrequently, making shorter forward eye movements, and fixating closer to the beginnings of two-character target words in sentences.DiscussionIn contrast with the findings for alphabetic languages, older Chinese readers appear to compensate for age-related reading difficulty by employing a more careful reading strategy. Age-related changes in reading strategy therefore appear to be language specific, rather than universal, and may reflect the specific visual and linguistic requirements of the writing system.

Associations between Tactile Sensory Threshold and Postural Performance and Effects of Healthy Aging and Subthreshold Vibrotactile Stimulation on Postural Outcomes in a Simple Dual Task.

Specific activities that require concurrent processing of postural and cognitive tasks may increase the risk for falls in older adults. We investigated whether peripheral receptor sensitivity was associated with postural performance in a dual-task and whether an intervention in form of subthreshold vibration could affect performance. Ten younger (age: 20–35 years) and ten older adults (70–85 years) performed repeated auditory-verbal 1-back tasks while standing quietly on a force platform. Foot sole vibration was randomly added during several trials. Several postural control and performance measures were assessed and statistically analyzed (significance set to α-levels of .05). There were moderate correlations between peripheral sensitivity and several postural performance and control measures (r = .45 to .59). Several postural performance measures differed significantly between older and younger adults (p < 0.05); addition of vibration did not affect outcome measures. Aging affects healthy older adults' performance in dual-tasks, and peripheral sensitivity may be a contributor to the observed differences. A vibration intervention may only be useful when there are more severe impairments of the sensorimotor system. Hence, future research regarding the efficacy of sensorimotor interventions in the form of vibrotactile stimulation should focus on older adults whose balance is significantly affected.

Effects of healthy aging and coronary artery disease on sympathetic axonal recruitment strategies during prolonged end-inspiratory apnea

Effects of healthy aging and coronary artery disease on sympathetic axonal recruitment strategies during prolonged end-inspiratory apnea

Overestimating the Effects of Healthy Aging

Overestimating the Effects of Healthy Aging

Reduced Haemodynamic Response in the Ageing Visual Cortex Measured by Absolute fNIRS.

The effect of healthy ageing on visual cortical activation is still to be fully explored. This study aimed to elucidate whether the haemodynamic response (HDR) of the visual cortex altered as a result of ageing. Visually normal (healthy) participants were presented with a simple visual stimulus (reversing checkerboard). Full optometric screening was implemented to identify two age groups: younger adults (n = 12, mean age 21) and older adults (n = 13, mean age 71). Frequency-domain Multi-distance (FD-MD) functional Near-Infrared Spectroscopy (fNIRS) was used to measure absolute changes in oxygenated [HbO] and deoxygenated [HbR] haemoglobin concentrations in the occipital cortices. Utilising a slow event-related design, subjects viewed a full field reversing checkerboard with contrast and check size manipulations (15 and 30 minutes of arc, 50% and 100% contrast). Both groups showed the characteristic response of increased [HbO] and decreased [HbR] during stimulus presentation. However, older adults produced a more varied HDR and often had comparable levels of [HbO] and [HbR] during both stimulus presentation and baseline resting state. Younger adults had significantly greater concentrations of both [HbO] and [HbR] in every investigation regardless of the type of stimulus displayed (p<0.05). The average variance associated with this age-related effect for [HbO] was 88% and [HbR] 91%. Passive viewing of a visual stimulus, without any cognitive input, showed a marked age-related decline in the cortical HDR. Moreover, regardless of stimulus parameters such as check size, the HDR was characterised by age. In concurrence with present neuroimaging literature, we conclude that the visual HDR decreases as healthy ageing proceeds.

Effects of healthy ageing on precision and binding of object location in visual short term memory.

Visual short term memory (STM) declines as people get older, but the nature of this deterioration is not well understood. We tested 139 healthy subjects (19–83 years) who were first required to identify a previously seen object and then report its location using a touchscreen. Results demonstrated an age-related decline in both object identification and localization. Deterioration in localization performance was apparent even when only 1 item had to be remembered, worsening disproportionately with increasing memory load. Thus, age-dependent memory degradation cannot be explained simply by a decrease in the number of items that can be held in visual STM but rather by the precision with which they are recalled. More important, there was no evidence for a significant decrease in object-location binding with increasing age. Thus, although precision for object identity and location declines with age, the ability to associate object identity to its location seems to remain unimpaired. As it has been reported that binding deficits in STM might be the first cognitive signs of early Alzheimer’s disease (AD), the finding that object-location binding processes are relatively intact with normal aging supports the possible suitability of using misbinding as an index measures for probing early diagnosis of AD.

The effects of healthy aging, amnestic mild cognitive impairment, and Alzheimer's disease on recollection and familiarity: a meta-analytic review.

It is well established that healthy aging, amnestic Mild Cognitive Impairment (aMCI), and Alzheimer's Disease (AD) are associated with substantial declines in episodic memory. However, there is still debate as to how two forms of episodic memory - recollection and familiarity - are affected by healthy and pathological aging. To address this issue we conducted a meta-analytic review of the effect sizes reported in studies using remember/know (RK), receiver operating characteristic (ROC) and process dissociation (PD) methods to examine recollection and familiarity in healthy aging (25 published reports), aMCI (9 published reports), and AD (5 published reports). The results from the meta-analysis revealed that healthy aging is associated with moderate-to-large recollection impairments. Familiarity was not impaired in studies using ROC or PD methods but was impaired in studies that used the RK procedure. aMCI was associated with large decreases in recollection whereas familiarity only tended to show a decrease in studies with a patient sample comprised of both single-domain and multiple-domain aMCI patients. Lastly, AD was associated with large decreases in both recollection and familiarity. The results are consistent with neuroimaging evidence suggesting that the hippocampus is critical for recollection whereas familiarity is dependent on the integrity of the surrounding perirhinal cortex. Moreover, the results highlight the relevance of method selection when examining aging, and suggest that familiarity deficits might be a useful behavioral marker for identifying individuals that will develop dementia.

Differences between patterns of brain activity associated with semantics and those linked with phonological processing diminish with age.

It is widely believed that language function tends to show little age-related performance decline. Indeed, some older individuals seem to use compensatory mechanisms to maintain a high level of performance when submitted to lexical tasks. However, how these mechanisms affect cortical and subcortical activity during semantic and phonological processing has not been extensively explored. The purpose of this study was to look at the effect of healthy aging on cortico-subcortical routes related to semantic and phonological processing using a lexical analogue of the Wisconsin Cart-Sorting Task. Our results indicate that while young adults tend to show increased activity in the ventrolateral prefrontal cortex, the dorsolateral prefrontal cortex, the fusiform gyrus, the ventral temporal lobe and the caudate nucleus during semantic decisions and in the posterior Broca's area (area 44), the temporal lobe (area 37), the temporoparietal junction (area 40) and the motor cortical regions during phonological decisions, older individuals showed increased activity in the dorsolateral prefrontal cortex and motor cortical regions during both semantic and phonological decisions. Furthermore, when semantic and phonological decisions were contrasted with each other, younger individuals showed significant brain activity differences in several regions while older individuals did not. Therefore, in older individuals, the semantic and phonological routes seem to merge into a single pathway. These findings represent most probably neural reserve/compensation mechanisms, characterized by a decrease in specificity, on which the elderly rely to maintain an adequate level of performance.