Age Differences In Effects Research Articles

Evolution of differential maternal age effects on male and female offspring development and longevity

Summary Maternal age effects on life‐history traits, including longevity, are widespread and can be seen as a manifestation of ageing. However, little is known about how maternal life span may influence the maternal age effect. At a given chronological age, a long‐lived parent may be at a younger biological age than a short‐lived parent and thus has a less severe parental age effect. However, earlier work using experimentally evolved short‐ and long‐lived lines did not support this hypothesis. We scored developmental time and longevity of 14 995 individual seed beetles, Callosobruchus maculatus derived from replicate short‐lived and long‐lived lines created via artificial selection on male life span. Offspring from older mothers had shorter life span, which is consistent with most of the literature. We found support for the hypothesis that detrimental maternal age effects evolve to be weaker under selection for long life span. However, this finding was only apparent in males, suggesting that maternal age affects male and female offspring differently. These results suggest that sex‐dependent parental age effects should be incorporated in the studies of longevity and ageing evolution and that selection on one sex can cause evolution of parental age effects in the other sex.

ALTERED FMRI ACTIVATION PATTERN DURING VISUAL SCENE ENCODING IN AFFECTED AND NON-AFFECTED CARRIERS OF PSEN1 AND APP MUTATIONS

Background: Several studies highlighted the differential effect of normal and pathological aging on hippocampal subfield volumes, suggesting that these measurements may be more accurate than global hippocampal volumetry to detect early Alzheimer’s disease (AD). For clinical application, validated automatic algorithms of hippocampal subfield segmentation are urgently needed. An increasing number of studies use the automatic segmentation algorithm implemented in FreeSurfer. However, this approach has not been validated so far on AD patients. This study aimed to compare the accuracy of T1-MRI-based FreeSurfer segmentation versus manual delineation on dedicated high-resolution scan in measuring hippocampal subfield volumes and the effects of age and AD on these volumes. Methods: Hippocampal subfields were segmented in 98 healthy individuals (aged 19 to 84), 17 MCI and 18 AD patients using both FreeSurfer (T1-MRI, resolution: 1*1*1mm) and manual delineation (proton density-MRI, resolution: 0.375*0.375*2mm). Intraclass correlation coefficients (ICC) and Bland-Altman plots were computed to assess the consistency between both methods, and the effects of age (regressions) and group (ANOVAs) were assessed for both Freesurfuer and manual measurements. Results: Moderate to high ICCs were found for the subiculum and other subfields as well as for the whole hippocampus, but the ICC was very low for CA1. Using manual delineation, age was found to have a linear effect on the subiculum and a nonlinear (later) effect on CA1 volumes. A graded effect of the pathology was found on CA1, subiculum and the other subfields volumes. FreeSurfer CA1 volumes were found to be lower than those obtained from manual segmentation. This bias was proportional to the volume of this structure so that no effect of age or AD could be detected on FreeSurfer CA1 volumes. Conclusions: This study highlights differences in the anatomic definition of the subfields, especially for CA1, between FreeSurfer and manual delineation based on histologic atlases. While FreeSurfer provides reasonable estimates of the subiculum and other subfields, it does not provide a reliable estimate of CA1 volume and fails in detecting normal aging and AD-related changes in this subfield. As earliest AD-related changes seem to occur in CA1, FreeSurfer needs to be improved especially for clinical application in early AD diagnosis.

Differential effects of age on large artery stiffness and minimal vascular resistance in normotensive and mildly hypertensive individuals

Large artery stiffness and small artery structural changes are both cardiovascular risk factors. Arterial stiffness increases with age and blood pressure (BP), but it is unclear in which way large artery pulse wave velocity (PWV) and peripheral vascular resistance are related and whether age has any influence. In a cross-sectional study, PWV and forearm minimum vascular resistance (Rmin ) was compared with emphasis on the impact of age. Normotensive (n = 53) and untreated hypertensive (n = 23) subjects were included based on 24-h BP measurements. Age ranged from 21 to 79 years with an even distribution from each age decade. PWV was assessed using tonometry. Forearm Rmin was measured by venous occlusion plethysmography at maximal vasodilatation induced by 10 min of ischaemia in combination with skin heating and hand grip exercise. In both normotensive and hypertensive subjects, PWV correlated significantly with age and BP. Based on median age, both groups were assigned into two equally large subgroups. Normotensive older (66 ± 7 years) and younger (35 ± 10 years) persons had different carotid-femoral PWV (7.9 ± 1.8 versus 5.7 ± 0.9 m/s, P<0.01), but similar Rmin values (3.7 ± 0.9 versus 3.6 ± 1.2 mmHg/ml/min/100 ml). Hypertensive older (63 ± 6 years) and younger (40 ± 10 years) also had different PWV (8.0 ± 1.5 versus 6.7 ± 1.1 m/s, P<0.05), but the older had lower Rmin (3.1 ± 0.8 versus 4.7 ± 2.2 mmHg/ml/min/100 ml, P<0.05). In a regression analysis adjusting for age, BP, gender and heart rate, no correlation was seen between PWV and Rmin . The data suggest that age differentially affects PWV and Rmin and that BP can increase in older persons without affecting Rmin .

Cognitive procedural learning among children and adolescents with or without spastic cerebral palsy: the differential effect of age.

Children learn to engage their surroundings skillfully, adopting implicit knowledge of complex regularities and associations. Probabilistic classification learning (PCL) is a type of cognitive procedural learning in which different cues are probabilistically associated with specific outcomes. Little is known about the effects of developmental disorders on cognitive skill acquisition. Twenty-four children and adolescents with cerebral palsy (CP) were compared to 24 typically developing (TD) youth in their ability to learn probabilistic associations. Performance was examined in relation to general cognitive abilities, level of motor impairment and age. Improvement in PCL was observed for all participants, with no relation to IQ. An age effect was found only among TD children. Learning curves of children with CP on a cognitive procedural learning task differ from those of TD peers and do not appear to be age sensitive.

Differential effects of aging on dendritic spines in visual cortex and prefrontal cortex of the rhesus monkey

Aging decreases the density of spines and the proportion of thin spines in the non-human primate (NHP) dorsolateral prefrontal cortex (dlPFC). In this study, we used confocal imaging of dye-loaded neurons to expand upon previous results regarding the effects of aging on spine density and morphology in the NHP dlPFC and compared these results to the effects of aging on pyramidal neurons in the primary visual cortex (V1). We confirmed that spine density, and particularly the density of thin spines, decreased with age in the dlPFC of rhesus monkeys. Furthermore, the average head diameter of non-stubby spines in the dlPFC was a better predictor than chronological age of the number of trials required to reach criterion on both the delayed response test of visuospatial working memory and the delayed nonmatching-to-sample test of recognition memory. By contrast, total spine density was lower on neurons in V1 than in dlPFC, and neither total spine density, thin spine density, nor spine size in V1 was affected by aging. Our results highlight the importance and selective vulnerability of dlPFC thin spines for optimal prefrontal-mediated cognitive function. Understanding the nature of the selective vulnerability of dlPFC thin spines as compared to the resilience of thin spines in V1 may be a promising area of research in the quest to prevent or ameliorate age-related cognitive decline.

Differences in effects of age and blood pressure on augmentation index.

The effect of age on the augmentation index (AI) differs between young adults and the elderly, and the AI reaches a plateau after the age of 60 years. We examined whether the effects of age and an elevation in blood pressure on the AI differ between young adults and the elderly, between subjects with and without high blood pressure, or between subjects with and without a high AI. The radial AI was measured in 10,190 subjects who were either healthy or had hypertension (n = 5,477 men and 4,743 women). In both sexes, a phased increase in the radial AI with age could only be confirmed up to an age of 60 years. A phased increase in the radial AI with the systolic blood pressure (SBP) could be confirmed up to an SBP of >170 mm Hg. Among subjects categorized within the highest age tertile, the highest SBP tertile, or the highest radial AI tertile, stepwise multivariable analyses demonstrated that SBP, but not age, was a significant independent factor influencing the radial AI. The effect of age and blood pressure on AI differ not only between young adults and the elderly but also between those with and those without high blood pressure or between those with and those without a high AI. The effect of an elevation in blood pressure, but not aging, on the AI is significant in the elderly, in subjects with high blood pressure, or in those with a high AI.

Aging differentially alters the expression of angiogenic genes in a tissue-dependent manner

Organ functions are altered and impaired during aging, thereby resulting in increased morbidity of age-related diseases such as Alzheimer’s disease, diabetes, and heart failure in the elderly. Angiogenesis plays a crucial role in the maintenance of tissue homeostasis, and aging is known to reduce the angiogenic capacity in many tissues. Here, we report the differential effects of aging on the expression of angiogenic factors in different tissues, representing a potentially causes for age-related metabolic disorders. PCR-array analysis revealed that many of angiogenic genes were down-regulated in the white adipose tissue (WAT) of aged mice, whereas they were largely up-regulated in the skeletal muscle (SM) of aged mice compared to that in young mice. Consistently, blood vessel density was substantially reduced and hypoxia was exacerbated in WAT of aged mice compared to that in young mice. In contrast, blood vessel density in SM of aged mice was well preserved and was not different from that in young mice. Moreover, we identified that endoplasmic reticulum (ER) stress was strongly induced in both WAT and SM during aging in vivo. We also found that ER stress significantly reduced the expression of angiogenic genes in 3T3-L1 adipocytes, whereas it increased their expression in C2C12 myotubes in vitro. These results collectively indicate that aging differentially affects the expression of angiogenic genes in different tissues, and that aging-associated down-regulation of angiogenic genes in WAT, at least in part through ER stress, is potentially involved in the age-related adipose tissue dysfunction.

Auditory Middle Latency Responses in Chronic Smokers Compared to Nonsmokers: Differential Effects of Stimulus and Age

Effects of clicks and tonebursts on early and late auditory middle latency response (AMLR) components were evaluated in young and older cigarette smokers and nonsmokers. Participants ( n = 49) were categorized by smoking and age into 4 groups: (a) older smokers, (b) older nonsmokers, (c) young smokers, and (d) young nonsmokers. Monaural, 2-channel AMLRs were acquired from Fz and Cz electrodes with 3 stimuli (clicks, 500 Hz, and 3000 Hz). Group differences included significantly higher V-Na amplitude in young adults and shorter Pb latency in older nonsmokers. Young smokers had a significantly higher Nb-Pb amplitude and shorter Nb latency than other groups. Toneburst stimuli yielded significantly longer V, Na, and Pa latencies compared to clicks. Pb latency was shorter at Fz than at Cz. Relative amplitudes were significantly higher at Fz than at Cz overall; Pa-Nb and Nb-Pb were significantly lower for 3000 Hz than for 500 Hz and clicks. Responses from young smokers revealed a higher amplitude and shorter latency for later AMLR waves, reflecting an arousal effect of smoking in cortical and subcortical generators. AMLR differences in older adults may be due to age-related neurochemical changes in the central nervous system. Stimulus and electrode differences plus smoking and aging effects can guide neurodiagnostic AMLR protocols, especially in young adult smokers.

Age-related decline in cognitive control: the role of fluid intelligence and processing speed

BackgroundResearch on cognitive control suggests an age-related decline in proactive control abilities whereas reactive control seems to remain intact. However, the reason of the differential age effect on cognitive control efficiency is still unclear. This study investigated the potential influence of fluid intelligence and processing speed on the selective age-related decline in proactive control. Eighty young and 80 healthy older adults were included in this study. The participants were submitted to a working memory recognition paradigm, assessing proactive and reactive cognitive control by manipulating the interference level across items.ResultsRepeated measures ANOVAs and hierarchical linear regressions indicated that the ability to appropriately use cognitive control processes during aging seems to be at least partially affected by the amount of available cognitive resources (assessed by fluid intelligence and processing speed abilities).ConclusionsThis study highlights the potential role of cognitive resources on the selective age-related decline in proactive control, suggesting the importance of a more exhaustive approach considering the confounding variables during cognitive control assessment.

Differential effect of immature embryo's age and genotypes on embryogenic type II callus production and whole plant regeneration in tropical maize inbred lines (Zea maysL.)

The study was undertaken to elucidate the effect of genotypes and age of immature embryo on callus induction, embryogenic type II calli production and regeneration from immature maize embryos. The immature embryos were excised from a selfed ear of ten elite Indian maize inbred lines on 6, 12 and 18 days after pollination. The mean callus induction, embryogenic type II calli production, and regeneration was highest across all the genotypes in 12 days old immature embryos and were 44.25, 26.12, and 11.20 per cent respectively. The significant differences were observed with respect to callus induction, embryogenic type II calli production and regeneration capacity between genotypes. The highest regeneration capacity was observed by immature embryo at 12 days after pollination (DAP) of genotype HKI1105 and CM300.

Complex Visual Search in Children and Adolescents: Effects of Age and Performance on fMRI Activation

Complex visuospatial processing relies on distributed neural networks involving occipital, parietal and frontal brain regions. Effects of physiological maturation (during normal brain development) and proficiency on tasks requiring complex visuospatial processing have not yet been studied extensively, as they are almost invariably interrelated. We therefore aimed at dissociating the effects of age and performance on functional MRI (fMRI) activation in a complex visual search task. In our cross-sectional study, healthy children and adolescents (n = 43, 19 females, 7-17 years) performed a complex visual search task during fMRI. Resulting activation was analysed with regard to the differential effects of age and performance. Our results are compatible with an increase in the neural network's efficacy with age: within occipital and parietal cortex, the core regions of the visual exploration network, activation increased with age, and more so in the right than in the left hemisphere. Further, activation outside the visual search network decreased with age, mainly in left inferior frontal, middle temporal, and inferior parietal cortex. High-performers had stronger activation in right superior parietal cortex, suggesting a more mature visual search network. We could not see effects of age or performance in frontal cortex. Our results show that effects of physiological maturation and effects of performance, while usually intertwined, can be successfully disentangled and investigated using fMRI in children and adolescents.

344: Differential effect of maternal age on fetal macrosomia in patients with diabetes class A2 and class B

344: Differential effect of maternal age on fetal macrosomia in patients with diabetes class A2 and class B

THE IMPORTANCE OF BEING ABLE TO DEAL WITH VARIABLES IN LEARNING SCIENCE

In a large-scale longitudinal study, 11-year-old schoolchildren were given a control-of-variables task, and their scores in this were related to their progress in learning about science at school over the next 3 years. The aim of the control-of-variables task was to measure children’s understanding that in a properly controlled scientific comparison one variable is tested at a time, while other variables are held constant. There were 2 kinds of question in the task. In one, the pupils were asked to judge whether particular comparisons between 2 situations were valid ones, in which all variables apart from the one being tested were held constant. In the other, they were asked to set up a valid comparison themselves. The pupils’ scores for both kinds of item successfully predicted their progress in science at school later on, even after controls for the effects of differences in age and IQ. Their success in setting up valid comparisons was a better predictor in the long term than the choices that they made in judging whether given comparisons were valid or not.

Brain glucose and acetoacetate metabolism: a comparison of young and older adults

The extent to which the age-related decline in regional brain glucose uptake also applies to other important brain fuels is presently unknown. Ketones are the brain's major alternative fuel to glucose, so we developed a dual tracer positron emission tomography protocol to quantify and compare regional cerebral metabolic rates for glucose and the ketone, acetoacetate. Twenty healthy young adults (mean age, 26 years) and 24 healthy older adults (mean age, 74 years) were studied. In comparison with younger adults, older adults had 8 ± 6% (mean ± SD) lower cerebral metabolic rates for glucose in gray matter as a whole (p = 0.035), specifically in several frontal, temporal, and subcortical regions, as well as in the cingulate and insula (p ≤ 0.01, false discovery rate correction). The effect of age on cerebral metabolic rates for acetoacetate in gray matter did not reach significance (p = 0.11). Rate constants (min−1) of glucose (Kg) and acetoacetate (Ka) were significantly lower (−11 ± 6%; [p = 0.005], and −19 ± 5%; [p = 0.006], respectively) in older adults compared with younger adults. There were differential effects of age on Kg and Ka as seen by significant interaction effects in the caudate (p = 0.030) and post-central gyrus (p = 0.023). The acetoacetate index, which expresses the scaled residuals of the voxel-wise linear regression of glucose on ketone uptake, identifies regions taking up higher or lower amounts of acetoacetate relative to glucose. The acetoacetate index was higher in the caudate of young adults when compared with older adults (p ≤ 0.05 false discovery rate correction). This study provides new information about glucose and ketone metabolism in the human brain and a comparison of the extent to which their regional use changes during normal aging.

Biochemical and Functional Characterization of the Klotho-VS Polymorphism Implicated in Aging and Disease Risk

Klotho (KL) is an age-regulating protein named after the Greek goddess who spins the thread of life. Mice deficient in KL are normal throughout development, but rapidly degenerate and display a variety of aging-associated abnormalities that eventually lead to decreased life expectancy. While multiple genetic association studies have identified KL polymorphisms linked with changes in disease risk, there is a paucity of concrete mechanistic data to explain how these amino acid substitutions alter KL protein function. The KLVS polymorphism is suggested to lead to changes in protein trafficking although the mechanism is unclear. Our studies have sought to further investigate the functional differences in the KLVS variant that result in increased risk of many age-related diseases. Our findings suggest that the F352V and C370S substitutions lead to alterations in processing as seen by differences in shedding and half-life. Their co-expression in KLVS results in a phenotype resembling wild-type, but despite this intragenic complementation there are still changes in homodimerization and interactions with FGFR1c. Taken together, these studies suggest that KLVS leads to altered homodimerization that indirectly leads to changes in processing and FGFR1c interactions. These findings help elucidate the functional differences that result from the VS polymorphism, which will help clarify how alterations in KL function can lead to human disease and affect cognition and lifespan.

Personality Maturation Around the World

During early adulthood, individuals from different cultures across the world tend to become more agreeable, more conscientious, and less neurotic. Two leading theories offer different explanations for these pervasive age trends: Five-factor theory proposes that personality maturation is largely determined by genetic factors, whereas social-investment theory proposes that personality maturation in early adulthood is largely the result of normative life transitions to adult roles. In the research reported here, we conducted the first systematic cross-cultural test of these theories using data from a large Internet-based sample of young adults from 62 nations (N = 884,328). We found strong evidence for universal personality maturation from early to middle adulthood, yet there were significant cultural differences in age effects on personality traits. Consistent with social-investment theory, results showed that cultures with an earlier onset of adult-role responsibilities were marked by earlier personality maturation.

Differential effects of aging on spatial contrast sensitivity to linear and polar sine-wave gratings

Changes in visual function beyond high-contrast acuity are known to take place during normal aging. We determined whether sensitivity to linear sine-wave gratings and to an elementary stimulus preferentially processed in extrastriate areas could be distinctively affected by aging. We measured spatial contrast sensitivity twice for concentric polar (Bessel) and vertical linear gratings of 0.6, 2.5, 5, and 20 cycles per degree (cpd) in two age groups (20-30 and 60-70 years). All participants were free of identifiable ocular disease and had normal or corrected-to-normal visual acuity. Participants were more sensitive to Cartesian than to polar gratings in all frequencies tested, and the younger adult group was more sensitive to all stimuli tested. Significant differences between sensitivities of the two groups were found for linear (only 20 cpd; P<0.01) and polar gratings (all frequencies tested; P<0.01). The young adult group was significantly more sensitive to linear than to circular gratings in the 20 cpd frequency. The older adult group was significantly more sensitive to linear than to circular gratings in all spatial frequencies, except in the 20 cpd frequency. The results suggest that sensitivity to the two kinds of stimuli is affected differently by aging. We suggest that neural changes in the aging brain are important determinants of this difference and discuss the results according to current models of human aging.

Differential effects of aging and sex on stroke induced inflammation across the lifespan

Aging and biological sex are critical determinants of stroke outcome. Post-ischemic inflammatory response strongly contributes to the extent of ischemic brain injury, but how this response changes with age and sex is unknown. We subjected young (5–6months), middle aged (14–15months) and aged (20–22months), C57BL/6 male and female mice to transient middle cerebral artery occlusion (MCAO) and found that a significant age by sex interaction influenced histological stroke outcomes. Acute functional outcomes were worse with aging. Neutrophils, inflammatory macrophages, macrophages, dendritic cells (DCs) and microglia significantly increased in the brain post MCAO. Cycling females had higher Gr1− non-inflammatory macrophages and lower T cells in the brain after stroke and these correlated with serum estradiol levels. Estrogen loss in acyclic aged female mice exacerbated stroke induced splenic contraction. Advanced age increased T cells, DCs and microglia at the site of injury, which may be responsible for the exacerbated behavioral deficits in the aged. We conclude that aging and sex have differential effects on the post stroke inflammatory milieu. Putative immunomodulatory therapies need to account for this heterogeneity.

Differential effects of duration and age on the consequences of neuroinflammation in the hippocampus

The current study investigated the hypothesis that the duration of the proinflammatory environment plays a critical role in the brain's response that results in negative consequences on cognition, biochemistry, and pathology. Lipopolysaccharide or artificial cerebrospinal fluid was slowly (250 ηg/h) infused into the fourth ventricle of young (3-month-old), adult (9-month-old), or aged (23-month-old) male F-344 rats for 21 or 56 days. The rats were then tested in the water pool task and endogenous hippocampal levels of pro- and anti-inflammatory proteins and genes and indicators of glutamatergic function were determined. The duration of the lipopolysaccharide infusion, compared with the age of the rat, had the greatest effect on (1) spatial working memory; (2) the density and distribution of activated microglia within the hippocampus; and (3) the cytokine protein and gene expression profiles within the hippocampus. The duration- and age-dependent consequences of neuroinflammation might explain why human adults respond positively to anti-inflammatory therapies and aged humans do not.

Differential effects of age on subcomponents of response inhibition

Inhibitory deficits contribute to cognitive decline in the aging brain. Separating subcomponents of response inhibition may help to resolve contradictions in the existing literature. A total of 49 healthy participants underwent functional magnetic resonance imaging (fMRI) while performing a Go/no-go-, a Simon-, and a Stop-signal task. Regression analyses were conducted to identify correlations of age and activation patterns. Imaging results revealed a differential effect of age on subcomponents of response inhibition. In a simple Go/no-go task (no spatial discrimination), aging was associated with increased activation of the core inhibitory network and parietal areas. In the Simon task, which required spatial discrimination, increased activation in additional inhibitory control regions was present. However, in the Stop-signal task, the most demanding of the three tasks, aging was associated with decreased activation. This suggests that older adults increasingly recruit the inhibitory network and, with increasing load, additional inhibitory regions. However, if inhibitory load exceeds compensatory capacity, performance declines in concert with decreasing activation. Thus, the present findings may refine current theories of cognitive aging.