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Effects of aging on lexical processing are well attested, but the picture is less clear for grammatical processing. Where age differences emerge, these are usually ascribed to working-memory (WM) decline. Previous studies on the influence of WM on agreement computation have yielded inconclusive results, and work on aging and subject-verb agreement processing is lacking. In two experiments (Experiment 1: timed grammaticality judgment, Experiment 2: self-paced reading + WM test), we investigated older (OA) and younger (YA) adults’ susceptibility to agreement attraction errors. We found longer reading latencies and judgment reaction times (RTs) for OAs. Further, OAs, particularly those with low WM scores, were more accepting of sentences with attraction errors than YAs. OAs showed longer reading latencies for ungrammatical sentences, again modulated by WM, than YAs. Our results indicate that OAs have greater difficulty blocking intervening nouns from interfering with the computation of agreement dependencies. WM can modulate this effect.
Normal aging is associated with a decline in different cognitive domains and local structural atrophy as well as decreases in dopamine concentration and receptor density. To date, it is largely unknown how these reductions in dopaminergic neurotransmission affect human brain regions responsible for reward-based decision making in older adults. Using a learning criterion in a probabilistic object reversal task, we found a learning stage by age interaction in the dorsolateral prefrontal cortex (dIPFC) during decision making. While young adults recruited the dlPFC in an early stage of learning reward associations, older adults recruited the dlPFC when reward associations had already been learned. Furthermore, we found a reduced change in ventral striatal BOLD signal in older as compared to younger adults in response to high probability rewards. Our data are in line with behavioral evidence that older adults show altered stimulus-reward learning and support the view of an altered fronto-striatal interaction during reward-based decision making in old age, which contributes to prolonged learning of reward associations.
Brown adipose tissue (BAT) is responsible for non-shivering thermogenesis, thereby allowing mammals to maintain a constant body temperature in a cold environment. Thermogenic capacity of this tissue is due to a high mitochondrial density and expression of uncoupling protein 1 (UCP1), a unique brown adipocyte marker which dissipates the mitochondrial proton gradient to produce heat instead of ATP. BAT is actively involved in whole-body metabolic homeostasis and during aging there is a loss of classical brown adipose tissue with concomitantly reduced browning capacity of white adipose tissue. Therefore, an age-dependent decrease of BAT-related energy expenditure capacity may exacerbate the development of metabolic diseases, including obesity and type 2 diabetes mellitus. Given that direct effects of age-related changes of BAT-metabolic flux have yet to be unraveled, the aim of the current thesis is to investigate potential metabolic mechanisms involved in BAT-dysfunction during aging and to identify suitable metabolic candidates as functional biomarkers of BAT-aging. To this aim, integration of transcriptomic, metabolomic and proteomic data analyses of BAT from young and aged mice was performed, and a group of candidates with age-related changes was revealed. Metabolomic analysis showed age-dependent alterations of metabolic intermediates involved in energy, nucleotide and vitamin metabolism, with major alterations regarding the purine nucleotide pool. These data suggest a potential role of nucleotide intermediates in age-related BAT defects. In addition, the screening of transcriptomic and proteomic data sets from BAT of young and aged mice allowed identification of a 60-kDa lysophospholipase, also known as L-asparaginase (Aspg), whose expression declines during BAT-aging. Involvement of Aspg in brown adipocyte thermogenic function was subsequently analyzed at the molecular level using in vitro approaches and animal models. The findings revealed sensitivity of Aspg expression to β3-adrenergic activation via different metabolic cues, including cold exposure and treatment with β3-adrenergic agonist CL. To further examine ASPG function in BAT, an over-expression model of Aspg in a brown adipocyte cell line was established and showed that these cells were metabolically more active compared to controls, revealing increased expression of the main brown-adipocyte specific marker UCP1, as well as higher lipolysis rates. An in vitro loss-of-function model of Aspg was also functionally analyzed, revealing reduced brown adipogenic characteristics and an impaired lipolysis, thus confirming physiological relevance of Aspg in brown adipocyte function. Characterization of a transgenic mouse model with whole-body inactivation of the Aspg gene (Aspg-KO) allowed investigation of the role of ASPG under in vivo conditions, indicating a mild obesogenic phenotype, hypertrophic white adipocytes, impairment of the early thermogenic response upon cold-stimulation and dysfunctional insulin sensitivity. Taken together, these data show that ASPG may represent a new functional biomarker of BAT-aging that regulates thermogenesis and therefore a potential target for the treatment of age-related metabolic disease.
Brain activation during active balancing and its behavioral relevance in younger and older adults
(2022)
Age-related deterioration of balance control is widely regarded as an important phenomenon influencing quality of life and longevity, such that a more comprehensive understanding of the neural mechanisms underlying this process is warranted.
Specifically, previous studies have reported that older adults typically show higher neural activity during balancing as compared to younger counterparts, but the implications of this finding on balance performance remain largely unclear.
Using functional near-infrared spectroscopy (fNIRS), differences in the cortical control of balance between healthy younger (n = 27) and older (n = 35) adults were explored.
More specifically, the association between cortical functional activity and balance performance across and within age groups was investigated. To this end, we measured hemodynamic responses (i.e., changes in oxygenated and deoxygenated hemoglobin) while participants balanced on an unstable device.
As criterion variables for brain-behavior-correlations, we also assessed postural sway while standing on a free-swinging platform and while balancing on wobble boards with different levels of difficulty.
We found that older compared to younger participants had higher activity in prefrontal and lower activity in postcentral regions.
Subsequent robust regression analyses revealed that lower prefrontal brain activity was related to improved balance performance across age groups, indicating that higher activity of the prefrontal cortex during balancing reflects neural inefficiency.
We also present evidence supporting that age serves as a moderator in the relationship between brain activity and balance, i.e., cortical hemodynamics generally appears to be a more important predictor of balance performance in the older than in the younger. Strikingly, we found that age differences in balance performance are mediated by balancing-induced activation of the superior frontal gyrus, thus suggesting that differential activation of this region reflects a mechanism involved in the aging process of the neural control of balance.
Our study suggests that differences in functional brain activity between age groups are not a mere by-product of aging, but instead of direct behavioral relevance for balance performance.
Potential implications of these findings in terms of early detection of fall-prone individuals and intervention strategies targeting balance and healthy aging are discussed.
There is accumulating evidence suggesting an association of numbers with physical space. However, the origin of such spatial-numerical associations (SNAs) is still debated. In the present study we investigated the development of two SNAs in a cross-sectional study involving children, young and middle-aged adults as well as the elderly: (1) the SNARC (spatial-numerical association of response codes) effect, reflecting a directional SNA; and (2) the numerical bisection bias in a line bisection task with numerical flankers. Results revealed a consistent SNARC effect in all age groups that continuously increased with age. In contrast, a numerical bisection bias was only observed for children and elderly participants, implying an U-shaped distribution of this bias across age groups. Additionally, individual SNARC effects and numerical bisection biases did not correlate significantly. We argue that the SNARC effect seems to be influenced by longer-lasting experiences of cultural constraints such as reading and writing direction and may thus reflect embodied representations. Contrarily, the numerical bisection bias may originate from insufficient inhibition of the semantic influence of irrelevant numerical flankers, which should be more pronounced in children and elderly people due to development and decline of cognitive control, respectively. As there is an ongoing debate on the origins of SNAs in general and the SNARC effect in particular, the present results are discussed in light of these differing accounts in an integrative approach. However, taken together, the present pattern of results suggests that different cognitive mechanisms underlie the SNARC effect and the numerical bisection bias.
Understanding the association between autonomic nervous system [ANS] function and brain morphology across the lifespan provides important insights into neurovisceral mechanisms underlying health and disease. Resting-state ANS activity, indexed by measures of heart rate [HR] and its variability [HRV] has been associated with brain morphology, particularly cortical thickness [CT]. While findings have been mixed regarding the anatomical distribution and direction of the associations, these inconsistencies may be due to sex and age differences in HR/HRV and CT. Previous studies have been limited by small sample sizes, which impede the assessment of sex differences and aging effects on the association between ANS function and CT. To overcome these limitations, 20 groups worldwide contributed data collected under similar protocols of CT assessment and HR/HRV recording to be pooled in a mega-analysis (N = 1,218 (50.5% female), mean age 36.7 years (range: 12-87)). Findings suggest a decline in HRV as well as CT with increasing age. CT, particularly in the orbitofrontal cortex, explained additional variance in HRV, beyond the effects of aging. This pattern of results may suggest that the decline in HRV with increasing age is related to a decline in orbitofrontal CT. These effects were independent of sex and specific to HRV; with no significant association between CT and HR. Greater CT across the adult lifespan may be vital for the maintenance of healthy cardiac regulation via the ANS-or greater cardiac vagal activity as indirectly reflected in HRV may slow brain atrophy. Findings reveal an important association between CT and cardiac parasympathetic activity with implications for healthy aging and longevity that should be studied further in longitudinal research.
In dieser Arbeit wird in mehreren Experimenten untersucht, wie gut junge und alte Erwachsene Sätze mit unterschiedlich komplexer syntaktischer Struktur verstehen können. Zentrales Thema dabei sind die Schwierigkeiten, die ältere Erwachsene mit der Objekt-vor-Subjekt-Wortstellung haben. Untersucht wird, inwiefern diese beobachteten Altersunterschiede durch eine reduzierte verbale Arbeitsgedächtniskapazität der älteren Erwachsenen erklärt werden können. Dabei stellt sich die Frage, ob die Defizite ein generelles verbales Arbeitsgedächtnis betreffen oder ob es ein eigenes Verarbeitungs-system für syntaktische Informationen gibt, dessen Kapazität mit dem Alter abnimmt. Es wurde versucht, die postulierte reduzierte Arbeitsgedächtniskapazität der älteren Erwachsenen an jungen Erwachsenen zu simulieren, indem deren Arbeitsgedächtniska-pazität durch eine Zusatzaufgabe künstlich eingeschränkt wurde. Weiterhin wurden die Altersunterschiede bei syntaktisch komplexen zentraleingebetteten Relativsätzen mit denen bei syntaktisch einfacheren koordinierten Hauptsätzen verglichen. Um die Studienteilnehmer mit den seltenen objektinitialen Strukturen zu konfrontieren und ihre Erfahrung mit solchen Sätzen zu verändern, wurden schließlich sowohl junge als auch alte Erwachsene mit Sätzen mit Objekt-vor-Subjekt-Wortstellung trainiert.
Multitalker situations confront listeners with a plethora of competing auditory inputs, and hence require selective attention to relevant information, especially when the perceptual saliency of distracting inputs is high. This study augmented the classical forced-attention dichotic listening paradigm by adding an interaural intensity manipulation to investigate developmental differences in the interplay between perceptual saliency and attentional control during auditory processing between early and middle childhood. We found that older children were able to flexibly focus on instructed auditory inputs from either the right or the left ear, overcoming the effects of perceptual saliency. In contrast, younger children implemented their attentional focus less efficiently. Direct comparisons of the present data with data from a recently published study of younger and older adults from our group suggest that younger children and older adults show similar levels of performance. Critically, follow-up comparisons revealed that younger children's performance restrictions reflect difficulties in attentional control only, whereas older adults' performance deficits also reflect an exaggerated reliance on perceptual saliency. We conclude that auditory attentional control improves considerably from middle to late childhood and that auditory attention deficits in healthy aging cannot be reduced to a simple reversal of child developmental improvements.
While much attention has been devoted to the cognition of aging multilingual individuals, little is known about how age affects their grammatical processing. We assessed subject-verb number-agreement processing in sixty native (L1) and sixty non-native (L2) speakers of German (age: 18-84) using a binary-choice sentence-completion task, along with various individual-differences tests. Our results revealed differential effects of age on L1 and L2 speakers' accuracy and reaction times (RTs). L1 speakers' RTs increased with age, and they became more susceptible to attraction errors. In contrast, L2 speakers' RTs decreased, once age-related slowing was controlled for, and their overall accuracy increased. We interpret this as resulting from increased L2 exposure. Moreover, L2 speakers' accuracy/RT patterns were more strongly affected by cognitive variables (working memory, interference control) than L1 speakers'. Our findings show that as regards bilinguals' grammatical processing ability, aging is associated with both gains (in experience) and losses (in cognitive abilities).
Objective: We investigated the effects of combined balance and strength training on measures of balance and muscle strength in older women with a history of falls.
Methods: Twenty-seven older women aged 70.4 ± 4.1 years (age range: 65 to 75 years) were randomly allocated to either an intervention (IG, n = 12) or an active control (CG, n = 15) group. The IG completed 8 weeks combined balance and strength training program with three sessions per week including visual biofeedback using force plates. The CG received physical therapy and gait training at a rehabilitation center. Training volumes were similar between the groups. Pre and post training, tests were applied for the assessment of muscle strength (weight-bearing squat [WBS] by measuring the percentage of body mass borne by each leg at different knee flexions [0°, 30°, 60°, and 90°], sit-to-stand test [STS]), and balance. Balance tests used the modified clinical test of sensory interaction (mCTSIB) with eyes closed (EC) and opened (EO), on stable (firm) and unstable (foam) surfaces as well as spatial parameters of gait such as step width and length (cm) and walking speed (cm/s).
Results: Significant group × time interactions were found for different degrees of knee flexion during WBS (0.0001 < p < 0.013, 0.441 < d < 0.762). Post hoc tests revealed significant pre-to-post improvements for both legs and for all degrees of flexion (0.0001 < p < 0.002, 0.697 < d < 1.875) for IG compared to CG. Significant group × time interactions were found for firm EO, foam EO, firm EC, and foam EC (0.006 < p < 0.029; 0.302 < d < 0.518). Post hoc tests showed significant pre-to-post improvements for both legs and for all degrees of oscillations (0.0001 < p < 0.004, 0.753 < d < 2.097) for IG compared to CG. This study indicates that combined balance and strength training improved percentage distribution of body weight between legs at different conditions of knee flexion (0°, 30°, 60°, and 90°) and also decreased the sway oscillation on a firm surface with eyes closed, and on foam surface (with eyes opened or closed) in the IG.
Conclusion: The higher positive effects of training seen in standing balance tests, compared with dynamic tests, suggests that balance training exercises including lateral, forward, and backward exercises improved static balance to a greater extent in older women.
Objective: We investigated the effects of combined balance and strength training on measures of balance and muscle strength in older women with a history of falls.
Methods: Twenty-seven older women aged 70.4 ± 4.1 years (age range: 65 to 75 years) were randomly allocated to either an intervention (IG, n = 12) or an active control (CG, n = 15) group. The IG completed 8 weeks combined balance and strength training program with three sessions per week including visual biofeedback using force plates. The CG received physical therapy and gait training at a rehabilitation center. Training volumes were similar between the groups. Pre and post training, tests were applied for the assessment of muscle strength (weight-bearing squat [WBS] by measuring the percentage of body mass borne by each leg at different knee flexions [0°, 30°, 60°, and 90°], sit-to-stand test [STS]), and balance. Balance tests used the modified clinical test of sensory interaction (mCTSIB) with eyes closed (EC) and opened (EO), on stable (firm) and unstable (foam) surfaces as well as spatial parameters of gait such as step width and length (cm) and walking speed (cm/s).
Results: Significant group × time interactions were found for different degrees of knee flexion during WBS (0.0001 < p < 0.013, 0.441 < d < 0.762). Post hoc tests revealed significant pre-to-post improvements for both legs and for all degrees of flexion (0.0001 < p < 0.002, 0.697 < d < 1.875) for IG compared to CG. Significant group × time interactions were found for firm EO, foam EO, firm EC, and foam EC (0.006 < p < 0.029; 0.302 < d < 0.518). Post hoc tests showed significant pre-to-post improvements for both legs and for all degrees of oscillations (0.0001 < p < 0.004, 0.753 < d < 2.097) for IG compared to CG. This study indicates that combined balance and strength training improved percentage distribution of body weight between legs at different conditions of knee flexion (0°, 30°, 60°, and 90°) and also decreased the sway oscillation on a firm surface with eyes closed, and on foam surface (with eyes opened or closed) in the IG.
Conclusion: The higher positive effects of training seen in standing balance tests, compared with dynamic tests, suggests that balance training exercises including lateral, forward, and backward exercises improved static balance to a greater extent in older women.
In addition to sensory decline, age-related losses in auditory perception also reflect impairments in attentional modulation of perceptual saliency. Using an attention and intensity-modulated dichotic listening paradigm, we investigated electrophysiological correlates of processing conflicts between attentional focus and perceptual saliency in 25 younger and 26 older adults. Participants were instructed to attend to the right or left ear, and perceptual saliency was manipulated by varying the intensities of both ears. Attentional control demand was higher in conditions when attentional focus and perceptual saliency favored opposing ears than in conditions without such conflicts. Relative to younger adults, older adults modulated their attention less flexibly and were more influenced by perceptual saliency. Our results show, for the first time, that in younger adults a late negativity in the event-related potential (ERP) at fronto-central and parietal electrodes was sensitive to perceptual-attentional conflicts during auditory processing (N450 modulation effect). Crucially, the magnitude of the N450 modulation effect correlated positively with task performance. In line with lower attentional flexibility, the ERP waveforms of older adults showed absence of the late negativity and the modulation effect. This suggests that aging compromises the activation of the frontoparietal attentional network when processing the competing and conflicting auditory information.
Repetitive, monotonic, and effortful voluntary muscle contractions performed for just a few weeks, i.e., resistance training, can substantially increase maximal voluntary force in the practiced task and can also increase gross motor performance. The increase in motor performance is often accompanied by neuroplastic adaptations in the central nervous system. While historical data assigned functional relevance to such adaptations induced by resistance training, this claim has not yet been systematically and critically examined in the context of motor performance across the lifespan in health and disease. A review of muscle activation, brain and peripheral nerve stimulation, and imaging data revealed that increases in motor performance and neuroplasticity tend to be uncoupled, making a mechanistic link between neuroplasticity and motor performance inconclusive. We recommend new approaches, including causal mediation analytical and hypothesis-driven models to substantiate the functional relevance of resistance training-induced neuroplasticity in the improvements of gross motor function across the lifespan in health and disease.
Older adults often experience hearing difficulties in multitalker situations. Attentional control of auditory perception is crucial in situations where a plethora of auditory inputs compete for further processing. We combined an intensity-modulated dichotic listening paradigm with attentional manipulations to study adult age differences in the interplay between perceptual saliency and attentional control of auditory processing. When confronted with two competing sources of verbal auditory input, older adults modulated their attention less flexibly and were more driven by perceptual saliency than younger adults. These findings suggest that aging severely impairs the attentional regulation of auditory perception.
Life and death of stationary linear response in anomalous continuous time random walk dynamics
(2014)
Linear theory of stationary response in systems at thermal equilibrium requires to find equilibrium correlation function of unperturbed responding system. Studies of the response of the systems exhibiting anomalously slow dynamics are often based on the continuous time random walk description (CTRW) with divergent mean waiting times. The bulk of the literature on anomalous response contains linear response functions like one by Cole-Cole calculated from such a CTRW theory and applied to systems at thermal equilibrium. Here we show within a fairly simple and general model that for the systems with divergent mean waiting times the stationary response at thermal equilibrium is absent, in accordance with some recent studies. The absence of such stationary response (or dying to zero non-stationary response in aging experiments) would confirm CTRW with divergent mean waiting times as underlying physical relaxation mechanism, but reject it otherwise. We show that the absence of stationary response is closely related to the breaking of ergodicity of the corresponding dynamical variable. As an important new result, we derive a generalized Cole-Cole response within ergodic CTRW dynamics with finite waiting time. Moreover, we provide a physically reasonable explanation of the origin and wide presence of 1/f noise in condensed matter for ergodic dynamics close to normal, rather than strongly deviating.
Remodeling of the extracellular matrix is a key component of the metabolic adaptations of adipose tissue in response to dietary and physiological challenges. Disruption of its integrity is a well-known aspect of adipose tissue dysfunction, for instance, during aging and obesity. Adipocyte regeneration from a tissue-resident pool of mesenchymal stem cells is part of normal tissue homeostasis. Among the pathophysiological consequences of adipogenic stem cell aging, characteristic changes in the secretory phenotype, which includes matrix-modifying proteins, have been described. Here, we show that the expression of the matricellular protein periostin, a component of the extracellular matrix produced and secreted by adipose tissue-resident interstitial cells, is markedly decreased in aged brown and white adipose tissue depots. Using a mouse model, we demonstrate that the adaptation of adipose tissue to adrenergic stimulation and high-fat diet feeding is impaired in animals with systemic ablation of the gene encoding for periostin. Our data suggest that loss of periostin attenuates lipid metabolism in adipose tissue, thus recapitulating one aspect of age-related metabolic dysfunction. In human white adipose tissue, periostin expression showed an unexpected positive correlation with age of study participants. This correlation, however, was no longer evident after adjusting for BMI or plasma lipid and liver function biomarkers. These findings taken together suggest that age-related alterations of the adipose tissue extracellular matrix may contribute to the development of metabolic disease by negatively affecting nutrient homeostasis.
Older adults demonstrate a slower speed of linguistic processing, including sentence processing. In nonlinguistic cognitive domains such as memory, research suggests that age-related slowing of processing speed may be a strategy adopted in order to avoid potential error and/or to spare “cognitive resources.” So far, very few studies have tested whether older adults’ slower processing speed in the linguistic domain has a strategic nature as well. To fill this gap, we tested whether older adults can maintain language processing accuracy when a faster processing speed is enforced externally. Specifically, we compared sentence comprehension accuracy in younger and older adults when sentences were presented at the participant’s median self-paced reading speed versus twice as fast. We hypothesized that an external speed increase will cause a smaller accuracy decline in older than younger adults because older adults tend to adopt self-paced processing speeds “further away” from their performance limits. The hypothesis was not confirmed: The decline in accuracy due to faster presentation did not differ by age group. Thus, we found no evidence for strategic nature of age-related slowing of sentence processing. On the basis of our experimental design, we suggest that the age-related slowing of sentence processing is caused not only by motor slowdown, but also by a slowdown in cognitive processing
Manganese (Mn) and zinc (Zn) are not only essential trace elements, but also potential exogenous risk factors for various diseases. Since the disturbed homeostasis of single metals can result in detrimental health effects, concerns have emerged regarding the consequences of excessive exposures to multiple metals, either via nutritional supplementation or parenteral nutrition. This study focuses on Mn-Zn-interactions in the nematode Caenorhabditis elegans (C. elegans) model, taking into account aspects related to aging and age-dependent neurodegeneration.
Manganese (Mn) and zinc (Zn) are not only essential trace elements, but also potential exogenous risk factors for various diseases. Since the disturbed homeostasis of single metals can result in detrimental health effects, concerns have emerged regarding the consequences of excessive exposures to multiple metals, either via nutritional supplementation or parenteral nutrition. This study focuses on Mn-Zn-interactions in the nematode Caenorhabditis elegans (C. elegans) model, taking into account aspects related to aging and age-dependent neurodegeneration.
Previous research with younger adults has revealed differences between native (L1) and non-native late-bilingual (L2) speakers with respect to how morphologically complex words are processed. This study examines whether these L1/L2 differences persist into old age. We tested masked-priming effects for derived and inflected word forms in older L1 and L2 speakers of German and compared them to results from younger L1 and L2 speakers on the same experiment (mean ages: 62 vs. 24). We found longer overall response times paired with better accuracy scores for older (L1 and L2) participants than for younger participants. The priming patterns, however, were not affected by chronological age. While both L1 and L2 speakers showed derivational priming, only the L1 speakers demonstrated inflectional priming. We argue that general performance in both L1 and L2 is affected by aging, but that the more profound differences between native and non-native processing persist into old age.