In Vivo Brain Glutathione is Higher in Older Age and Correlates with Mobility

2020 ◽  
Author(s):  
K. E. Hupfeld ◽  
H. W. Hyatt ◽  
P. Alvarez Jerez ◽  
M. Mikkelsen ◽  
C. J. Hass ◽  
...  

AbstractBrain markers of oxidative damage increase with advancing age. In response, brain antioxidant levels may also increase with age, although this has not been well investigated. Here we used edited magnetic resonance spectroscopy to quantify endogenous levels of glutathione (GSH, one of the most abundant brain antioxidants) in 37 young (mean: 21.8 (2.5) years; 19 F) and 23 older adults (mean: 72.8 (8.9) years; 19 F). Accounting for age-related atrophy, we identified higher frontal and sensorimotor GSH levels for the older compared to the younger adults. For the older adults only, higher sensorimotor (but not frontal) GSH was correlated with poorer balance, gait, and manual dexterity. This suggests a regionally-specific relationship between higher brain oxidative stress levels and motor performance declines with age. We suggest these findings reflect a compensatory upregulation of GSH in response to increasing brain oxidative stress with normal aging. Together, these results provide insight into age differences in brain antioxidant levels and implications for motor function.

2019 ◽  
Author(s):  
Jordan D. Chamberlain ◽  
Holly Gagnon ◽  
Poortata Lalwani ◽  
Kaitlin E. Cassady ◽  
Molly Simmonite ◽  
...  

AbstractAge-related neural dedifferentiation – reduced distinctiveness of neural representations in the aging brain– has been associated with age-related declines in cognitive abilities. But why does neural distinctiveness decline with age? Based on prior work in non-human primates, we hypothesized that the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) declines with age and is associated with neural dedifferentiation. To test this hypothesis, we used magnetic resonance spectroscopy (MRS) to measure GABA and functional MRI (fMRI) to measure neural distinctiveness in the ventral visual cortex in a set of older and younger participants. Relative to younger adults, older adults exhibited lower GABA levels and less distinct activation patterns for faces and houses in the ventral visual cortex. Furthermore, individual differences in GABA within older adults predicted individual differences in neural distinctiveness even after controlling for gray matter volume and age. These results provide novel support for the view that age-related reductions of GABA contribute to age-related reductions in neural distinctiveness (i.e., neural dedifferentiation) in the human ventral visual cortex.Significance StatementNeural representations in the ventral visual cortex are less distinguishable in older compared to younger humans, and this neural dedifferentiation is associated with age-related cognitive deficits. Animal models suggest that reductions in the inhibitory neurotransmitter gamma aminobutyric acid (GABA) may play a role. To investigate this hypothesis, we combined functional magnetic resonance imaging (fMRI) and magnetic resonance spectroscopy (MRS) in a study of the human ventral visual cortex. We observed reduced distinctiveness of neural patterns and reduced GABA levels in older compared to younger adults. Furthermore, older adults with higher GABA levels tended to have more distinctive neural representations. These findings suggest that reduced GABA levels contribute to age-related declines in neural distinctiveness in the human ventral visual cortex.


2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Tamara Simpson ◽  
Matthew Pase ◽  
Con Stough

The detrimental effect of neuronal cell death due to oxidative stress and mitochondrial dysfunction has been implicated in age-related cognitive decline and neurodegenerative disorders such as Alzheimer’s disease. The Indian herbBacopa monnieriis a dietary antioxidant, with animal andin vitrostudies indicating several modes of action that may protect the brain against oxidative damage. In parallel, several studies using the CDRI08 extract have shown that extracts ofBacopa monnieriimprove cognitive function in humans. The biological mechanisms of this cognitive enhancement are unknown. In this review we discuss the animal studies andin vivoevidence forBacopa monnierias a potential therapeutic antioxidant to reduce oxidative stress and improve cognitive function. We suggest that future studies incorporate neuroimaging particularly magnetic resonance spectroscopy into their randomized controlled trials to better understand whether changes in antioxidant statusin vivocause improvements in cognitive function.


2018 ◽  
Author(s):  
Poortata Lalwani ◽  
Holly Gagnon ◽  
Kaitlin Cassady ◽  
Molly Simmonite ◽  
Scott Peltier ◽  
...  

AbstractNeural activation patterns in the ventral visual cortex in response to different categories of visual stimuli (e.g., faces vs. houses) are less selective, or distinctive, in older adults than in younger adults, a phenomenon known as age-related neural dedifferentiation. Previous work in animals suggests that age-related reductions of the inhibitory neurotransmitter, gamma aminobutyric acid (GABA), may play a role in this age-related decline in neural distinctiveness. In this study, we investigated whether neural dedifferentiation extends to auditory cortex and whether individual differences in GABA are associated with individual differences in neural distinctiveness in humans. 20 healthy young adults (ages 18-29) and 23 healthy older adults (over 65) completed a functional magnetic resonance imaging (fMRI) scan, during which neural activity was estimated while they listened to foreign speech and music. GABA levels in the auditory, ventrovisual and sensorimotor cortex were estimated in the same individuals in a separate magnetic resonance spectroscopy (MRS) scan. Relative to the younger adults, the older adults exhibited both (1) less distinct activation patterns for music vs. speech stimuli and (2) lower GABA levels in the auditory cortex. Also, individual differences in auditory GABA levels (but not ventrovisual or sensorimotor GABA levels) predicted individual differences in neural distinctiveness in the auditory cortex in the older adults. These results demonstrate that age-related neural dedifferentiation extends to the auditory cortex and suggest that declining GABA levels may play a role in neural dedifferentiation in older adults.Significance StatementPrior work has revealed age-related neural dedifferentiation in the visual cortex. GABA levels also decline with age in several parts of the human cortex. Here, we report that these two age-related changes are linked; neural dedifferentiation is associated with lower GABA levels in older adults. We also show that age-related neural dedifferentiation extends to auditory cortex, suggesting that it may be a general feature of the aging brain. These findings provide novel insights into the neurochemical basis of age-related neural dedifferentiation in humans and also offer a potential new avenue for investigating age-related declines in central auditory processing.


2021 ◽  
Author(s):  
Jamie Murray ◽  
David Donaldson

Healthy aging leads to a significant decline in episodic memory, producing a reduction in thelikelihood of successful recollection, such that older adults remember less than younger adults.Emerging evidence from behavioral and neuroimaging studies demonstrate that recollectedinformation can also be more or less precise, highlighting a source of variability in memoryperformance not typically considered in studies of aging. Consequently, it is unknown whetherolder adults, compared to younger adults, only show a significant reduction in recollection rate or also exhibit a decline in recollection precision. Here, we provide new insight into age-relatedmemory decline by employing a novel source task that allows us to examine both the quantity(rate) and quality (precision) of episodic memory retrieval. First, we validated our task,demonstrating that it can effectively capture variability in both the rate and precision in olderadults. Second, we directly compared younger and older adults’ performance as a function ofstudy-test delay, showing significant reductions in both the rate and precision of recollectionwith age. Finally, we asked whether age-related changes in recollection can be accounted for bya reduction in attention, revealing that the division of attention in young adults results in areduction in rate but shows little evidence for a change in precision. Our results raise questionsabout the nature of age-related memory decline, highlighting the importance of measuring boththe quality and quantity of memory, and suggest new routes to achieve the early detection anddiagnosis of abnormal aging deficits.


2012 ◽  
Vol 37 (1) ◽  
pp. 88-99 ◽  
Author(s):  
Ryan G. Larsen ◽  
Damien M. Callahan ◽  
Stephen A. Foulis ◽  
Jane A. Kent-Braun

There is discrepancy in the literature regarding the degree to which old age affects muscle bioenergetics. These discrepancies are likely influenced by several factors, including variations in physical activity (PA) and differences in the muscle group investigated. To test the hypothesis that age may affect muscles differently, we quantified oxidative capacity of tibialis anterior (TA) and vastus lateralis (VL) muscles in healthy, relatively sedentary younger (8 YW, 8 YM; 21–35 years) and older (8 OW, 8 OM; 65–80 years) adults. To investigate the effect of physical activity on muscle oxidative capacity in older adults, we compared older sedentary women to older women with mild-to-moderate mobility impairment and lower physical activity (OIW, n = 7), and older sedentary men with older active male runners (OAM, n = 6). Oxidative capacity was measured in vivo as the rate constant, kPCr, of postcontraction phosphocreatine recovery, obtained by31P magnetic resonance spectroscopy following maximal isometric contractions. While kPCrwas higher in TA of older than activity-matched younger adults (28%; p = 0.03), older adults had lower kPCrin VL (23%; p = 0.04). In OIW compared with OW, kPCrwas lower in VL (∼45%; p = 0.01), but not different in TA. In contrast, OAM had higher kPCrthan OM (p = 0.03) in both TA (41%) and VL (54%). In older adults, moderate-to-vigorous PA was positively associated with kPCrin VL (r = 0.65, p < 0.001) and TA (r = 0.41, p = 0.03). Collectively, these results indicate that age-related changes in oxidative capacity vary markedly between locomotory muscles, and that altered PA behavior may play a role in these changes.


2019 ◽  
Vol 62 (5) ◽  
pp. 1258-1277 ◽  
Author(s):  
Megan K. MacPherson

PurposeThe aim of this study was to determine the impact of cognitive load imposed by a speech production task on the speech motor performance of healthy older and younger adults. Response inhibition, selective attention, and working memory were the primary cognitive processes of interest.MethodTwelve healthy older and 12 healthy younger adults produced multiple repetitions of 4 sentences containing an embedded Stroop task in 2 cognitive load conditions: congruent and incongruent. The incongruent condition, which required participants to suppress orthographic information to say the font colors in which color words were written, represented an increase in cognitive load relative to the congruent condition in which word text and font color matched. Kinematic measures of articulatory coordination variability and movement duration as well as a behavioral measure of sentence production accuracy were compared between groups and conditions and across 3 sentence segments (pre-, during-, and post-Stroop).ResultsIncreased cognitive load in the incongruent condition was associated with increased articulatory coordination variability and movement duration, compared to the congruent Stroop condition, for both age groups. Overall, the effect of increased cognitive load was greater for older adults than younger adults and was greatest in the portion of the sentence in which cognitive load was manipulated (during-Stroop), followed by the pre-Stroop segment. Sentence production accuracy was reduced for older adults in the incongruent condition.ConclusionsIncreased cognitive load involving response inhibition, selective attention, and working memory processes within a speech production task disrupted both the stability and timing with which speech was produced by both age groups. Older adults' speech motor performance may have been more affected due to age-related changes in cognitive and motoric functions that result in altered motor cognition.


2019 ◽  
Author(s):  
Debbie Marianne Yee ◽  
Sarah L Adams ◽  
Asad Beck ◽  
Todd Samuel Braver

Motivational incentives play an influential role in value-based decision-making and cognitive control. A compelling hypothesis in the literature suggests that the brain integrates the motivational value of diverse incentives (e.g., motivational integration) into a common currency value signal that influences decision-making and behavior. To investigate whether motivational integration processes change during healthy aging, we tested older (N=44) and younger (N=54) adults in an innovative incentive integration task paradigm that establishes dissociable and additive effects of liquid (e.g., juice, neutral, saltwater) and monetary incentives on cognitive task performance. The results reveal that motivational incentives improve cognitive task performance in both older and younger adults, providing novel evidence demonstrating that age-related cognitive control deficits can be ameliorated with sufficient incentive motivation. Additional analyses revealed clear age-related differences in motivational integration. Younger adult task performance was modulated by both monetary and liquid incentives, whereas monetary reward effects were more gradual in older adults and more strongly impacted by trial-by-trial performance feedback. A surprising discovery was that older adults shifted attention from liquid valence toward monetary reward throughout task performance, but younger adults shifted attention from monetary reward toward integrating both monetary reward and liquid valence by the end of the task, suggesting differential strategic utilization of incentives. Together these data suggest that older adults may have impairments in incentive integration, and employ different motivational strategies to improve cognitive task performance. The findings suggest potential candidate neural mechanisms that may serve as the locus of age-related change, providing targets for future cognitive neuroscience investigations.


2020 ◽  
Author(s):  
Samina Rahman ◽  
Victoria Kordovski ◽  
Savanna Tierney ◽  
Steven Paul Woods

Objective: Online banking is becoming increasingly common among older adults, whomay experience difficulties effectively navigating this instrumental technology. Thisstudy examined age effects on a performance-based Internet banking task and itsassociation with neurocognitive ability and functional capacity in older and youngeradults. Method: Thirty-five older adults and 50 younger adults completed anexperimenter-controlled online banking measure in which they independentlyperformed a series of naturalistic financial tasks (e.g., account transfers, bill paying).Participants also completed a standardized battery of neuropsychological tests andmeasures of functional capacity. Results: Older adults were markedly slower and lessaccurate in completing the Internet-based banking task, which was not confounded byother demographic, mood, or computer use factors. Higher scores on measures ofneurocognition and financial functional capacity were both strongly associated withhigher Internet-based banking task accuracy scores and quicker completion times inthe older, but not the younger adults. Conclusions: Findings suggest that older adultsexperience difficultly quickly and accurately navigating online banking platforms, whichmay be partly related to age-related declines in neurocognitive functions and basicfinancial capacity. Future studies might examine whether neurocognitive approaches toremediation and compensation can be used to improve online banking capacity inolder adults.


Antioxidants ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 507
Author(s):  
Rosaria Meccariello ◽  
Stefania D’Angelo

Aging and, particularly, the onset of age-related diseases are associated with tissue dysfunction and macromolecular damage, some of which can be attributed to accumulation of oxidative damage. Recently, growing interest has emerged on the beneficial effects of plant-based diets for the prevention of chronic diseases including obesity, diabetes, and cardiovascular disease. Several studies collectively suggests that the intake of polyphenols and their major food sources may exert beneficial effects on improving insulin resistance and related diabetes risk factors, such as inflammation and oxidative stress. They are the most abundant antioxidants in the diet, and their intake has been associated with a reduced aging in humans. Polyphenolic intake has been shown to be effective at ameliorating several age-related phenotypes, including oxidative stress, inflammation, impaired proteostasis, and cellular senescence, both in vitro and in vivo. In this paper, effects of these phytochemicals (either pure forms or polyphenolic-food) are reviewed and summarized according to affected cellular signaling pathways. Finally, the effectiveness of the anti-aging preventive action of nutritional interventions based on diets rich in polyphenolic food, such as the diets of the Blue zones, are discussed.


Author(s):  
Olga Wronikowska ◽  
Maria Zykubek ◽  
Agnieszka Michalak ◽  
Anna Pankowska ◽  
Paulina Kozioł ◽  
...  

AbstractMephedrone is a widely used drug of abuse, exerting its effects by interacting with monoamine transporters. Although this mechanism has been widely studied heretofore, little is known about the involvement of glutamatergic transmission in mephedrone effects. In this study, we comprehensively evaluated glutamatergic involvement in rewarding effects of mephedrone using an interdisciplinary approach including (1) behavioural study on effects of memantine (non-selective NMDA antagonist) on expression of mephedrone-induced conditioned place preference (CPP) in rats; (2) evaluation of glutamate concentrations in the hippocampus of rats following 6 days of mephedrone administration, using in vivo magnetic resonance spectroscopy (MRS); and (3) determination of glutamate levels in the hippocampus of rats treated with mephedrone and subjected to MRS, using ion-exchange chromatography. In the presented research, we confirmed priorly reported mephedrone-induced rewarding effects in the CPP paradigm and showed that memantine (5 mg/kg) was able to reverse the expression of this effect. MRS study showed that subchronic mephedrone administration increased glutamate level in the hippocampus when measured in vivo 24 h (5 mg/kg, 10 mg/kg and 20 mg/kg) and 2 weeks (5 mg/kg and 20 mg/kg) after last injection. Ex vivo chromatographic analysis did not show significant changes in hippocampal glutamate concentrations; however, it showed similar results as obtained in the MRS study proving its validity. Taken together, the presented study provides new insight into glutamatergic involvement in rewarding properties of mephedrone.


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