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Article ; Online: Investigating the effects of age and prior military service on fluid and crystallized cognitive functions using virtual morris water maze (vMWM) and NIH Toolbox tasks.

Mollusky, Adina / Reynolds-Lallement, Nadjalisse / Lee, Dylan / Zhong, Jimmy Y / Magnusson, Kathy R

2023 Volume 116, Page(s) 105156

Abstract: Much of current knowledge of aging involves war veterans and research about age-related cognitive changes in veterans involves generalized or single function tests or health or neurological disorders. The current study examined military service within ... ...

Abstract	Much of current knowledge of aging involves war veterans and research about age-related cognitive changes in veterans involves generalized or single function tests or health or neurological disorders. The current study examined military service within the context of comparisons of young and old humans involving generally healthy individuals to address normal age-associated cognitive changes. Adult participants included 11 young females (8 non-veterans; 3 veterans; 21-31 years), 5 young males (non-veterans, 21-24 years), 9 older females (non-veterans, 62-80 years), and 21 older males (11 non-veterans; 10 veterans; 60-86 years). They were tested in virtual Morris water maze (vMWM) tasks, which were designed to test spatial learning, cognitive flexibility and working memory, similar to rodent studies, and were validated by correlations with specific NIH Toolbox (NIH-TB) Cognitive Battery or Wechsler Memory Scale (WMS) Logical Memory I and II tests. Significant age-related deficits were seen on multiple vMWM tasks and NIH-TB fluid cognition tasks. Among older males, vMWM tasks appeared to be more sensitive, based on finding statistical differences, to prior military service than NIH Toolbox tasks. Compared with male non-veterans of comparable age and younger, older male veterans exhibited significant deficits in spatial learning, cognitive flexibility, and working memory on vMWM tasks. Our findings support continued development and characterization of vMWM tasks that are comparable between rodents and humans for translating aging interventions between species, and provide impetus for larger investigations examining the extent to which prior military service can serve as a "hidden" variable in normal biological declines of cognitive functions.
MeSH term(s)	Female ; Humans ; Male ; Morris Water Maze Test ; Maze Learning ; Cognition ; Aging
Language	English
Publishing date	2023-08-12
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	603162-6
ISSN	1872-6976 ; 0167-4943
ISSN (online)	1872-6976
ISSN	0167-4943
DOI	10.1016/j.archger.2023.105156
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Article ; Online: Multivitamin/Multimineral Supplementation Prevents or Reverses Decline in Vitamin Biomarkers and Cellular Energy Metabolism in Healthy Older Men: A Randomized, Double-Blind, Placebo-Controlled Study.

Michels, Alexander J / Butler, Judy A / Uesugi, Sandra L / Lee, Ken / Frei, Balz B / Bobe, Gerd / Magnusson, Kathy R / Hagen, Tory M

Nutrients

2023 Volume 15, Issue 12

Abstract: Despite the reported prevalence of micronutrient deficiencies in older adults, it is not yet established whether multivitamin/multimineral (MV/MM) supplements improve blood micronutrient status in individuals over the age of 65. Therefore, a cohort of 35 ...

Abstract	Despite the reported prevalence of micronutrient deficiencies in older adults, it is not yet established whether multivitamin/multimineral (MV/MM) supplements improve blood micronutrient status in individuals over the age of 65. Therefore, a cohort of 35 healthy men (>67 years) was recruited for an MV/MM supplementation trial. The primary endpoint was, as an indicator of micronutrient status, changes in blood micronutrient biomarkers from baseline to at least six months of supplementation with MV/MM or placebo. The secondary endpoint was basal O
MeSH term(s)	Male ; Humans ; Aged ; Vitamins ; Dietary Supplements ; Minerals ; Trace Elements ; Micronutrients ; Biomarkers ; Energy Metabolism ; Double-Blind Method
Chemical Substances	Vitamins ; Minerals ; Trace Elements ; Micronutrients ; Biomarkers
Language	English
Publishing date	2023-06-09
Publishing country	Switzerland
Document type	Randomized Controlled Trial ; Journal Article
ZDB-ID	2518386-2
ISSN	2072-6643 ; 2072-6643
ISSN (online)	2072-6643
ISSN	2072-6643
DOI	10.3390/nu15122691
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Article ; Online: Effects of zinc status on age-related T cell dysfunction and chronic inflammation.

Wong, Carmen P / Magnusson, Kathy R / Sharpton, Thomas J / Ho, Emily

Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine

2021 Volume 34, Issue 2, Page(s) 291–301

Abstract: Age-related T cell dysfunction contributes to immunosenescence and chronic inflammation. Aging is also associated with a progressive decline in zinc status. Zinc is an essential micronutrient critical for immune function. A significant portion of the ... ...

Abstract	Age-related T cell dysfunction contributes to immunosenescence and chronic inflammation. Aging is also associated with a progressive decline in zinc status. Zinc is an essential micronutrient critical for immune function. A significant portion of the older populations are at risk for marginal zinc deficiency. The combined impact of dietary zinc deficiency and age on immune dysfunction has not been well explored despite the common occurrence together in the elderly population. We hypothesize that age-related zinc loss contributes to T cell dysfunction and chronic inflammation in the elderly and is exacerbated by inadequate dietary intake and improved with zinc supplementation. Using an aging mouse model, the effects of marginal zinc deficiency and zinc supplementation on Th1/Th17/proinflammatory cytokine profiles and CD4
MeSH term(s)	Aging/drug effects ; Animals ; Chronic Disease ; Cytokines/antagonists & inhibitors ; Cytokines/biosynthesis ; Dietary Supplements ; Inflammation/drug therapy ; Inflammation/metabolism ; Inflammation/pathology ; Lipopolysaccharides/antagonists & inhibitors ; Lipopolysaccharides/pharmacology ; Male ; Mice ; Mice, Inbred C57BL ; T-Lymphocytes/drug effects ; T-Lymphocytes/metabolism ; Zinc/administration & dosage ; Zinc/blood ; Zinc/pharmacology
Chemical Substances	Cytokines ; Lipopolysaccharides ; Zinc (J41CSQ7QDS)
Language	English
Publishing date	2021-01-03
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	1112688-7
ISSN	1572-8773 ; 0966-0844
ISSN (online)	1572-8773
ISSN	0966-0844
DOI	10.1007/s10534-020-00279-5
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Article: Aging of the NMDA receptor: from a mouse's point of view.

Magnusson, Kathy R

Future neurology

2012 Volume 7, Issue 5, Page(s) 627–637

Abstract: Our elderly population is growing and declines in cognitive abilities, such as memory, can be costly, because it can interfere with a person's ability to live independently. The NMDA receptor is very important for many different forms of memory and this ... ...

Abstract	Our elderly population is growing and declines in cognitive abilities, such as memory, can be costly, because it can interfere with a person's ability to live independently. The NMDA receptor is very important for many different forms of memory and this receptor is negatively affected by aging. This review examines the progress that has been made recently in characterizing selective vulnerabilities of different subunits and splice variants of the NMDA receptor to normal aging in C57BL/6 mice. Evidence is also presented for changes in the relationships of NMDA receptors to plasticity across aging. Recent interventions show that enhancing NMDA receptors in aged individuals is associated with improvements in memory, but mouse models of neurodegenerative diseases suggest that finding the right balance between too little and too much NMDA receptor activity will be the key to enhancing memory without inducing pathology.
Language	English
Publishing date	2012-06-28
Publishing country	England
Document type	Journal Article
ISSN	1479-6708
ISSN	1479-6708
DOI	10.2217/fnl.12.54
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Article ; Online: Strategies to protect against age-related mitochondrial decay: Do natural products and their derivatives help?

Visioli, Francesco / Ingram, Avery / Beckman, Joseph S / Magnusson, Kathy R / Hagen, Tory M

Free radical biology & medicine

2021 Volume 178, Page(s) 330–346

Abstract: Mitochondria serve vital roles critical for overall cellular function outside of energy transduction. Thus, mitochondrial decay is postulated to be a key factor in aging and in age-related diseases. Mitochondria may be targets of their own decay through ... ...

Abstract	Mitochondria serve vital roles critical for overall cellular function outside of energy transduction. Thus, mitochondrial decay is postulated to be a key factor in aging and in age-related diseases. Mitochondria may be targets of their own decay through oxidative damage. However, treating animals with antioxidants has been met with only limited success in rejuvenating mitochondrial function or in increasing lifespan. A host of nutritional strategies outside of using traditional antioxidants have been devised to promote mitochondrial function. Dietary compounds are under study that induce gene expression, enhance mitochondrial biogenesis, mitophagy, or replenish key metabolites that decline with age. Moreover, redox-active compounds may now be targeted to mitochondria which improve their effectiveness. Herein we review the evidence that representative dietary effectors modulate mitochondrial function by stimulating their renewal or reversing the age-related loss of key metabolites. While in vitro evidence continues to accumulate that many of these compounds benefit mitochondrial function and/or prevent their decay, the results using animal models and, in some instances human clinical trials, are more mixed and sometimes even contraindicated. Thus, further research on optimal dosage and age of intervention are warranted before recommending potential mitochondrial rejuvenating compounds for human use.
MeSH term(s)	Animals ; Antioxidants/metabolism ; Antioxidants/pharmacology ; Biological Products/metabolism ; Biological Products/pharmacology ; Humans ; Mitochondria/metabolism ; Mitophagy ; Oxidative Stress
Chemical Substances	Antioxidants ; Biological Products
Language	English
Publishing date	2021-12-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	807032-5
ISSN	1873-4596 ; 0891-5849
ISSN (online)	1873-4596
ISSN	0891-5849
DOI	10.1016/j.freeradbiomed.2021.12.008
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Zs.A 2109: Show issues

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Article ; Online: Higher Levels of Protein Palmitoylation in the Frontal Cortex across Aging Were Associated with Reference Memory and Executive Function Declines.

Zamzow, Daniel R / Elias, Valerie / Acosta, Varinia A / Escobedo, Emily / Magnusson, Kathy R

eNeuro

2019 Volume 6, Issue 1

Abstract: Cognitive decline with aging is often due to altered levels of protein expression. The NMDA receptor (NMDAR) and the complex of proteins surrounding the receptor are susceptible to age-related changes in expression. In the frontal cortex of aged mice, ... ...

Abstract	Cognitive decline with aging is often due to altered levels of protein expression. The NMDA receptor (NMDAR) and the complex of proteins surrounding the receptor are susceptible to age-related changes in expression. In the frontal cortex of aged mice, there is a significant loss of expression of the GluN2B subunit of the NMDAR, an increase in Fyn expression, and no change in PSD-95. Studies have also found that, in the frontal cortex, phosphorylation of GluN2B subunits and palmitoylation of GluN2 subunits and NMDAR complex proteins are affected by age. In this study, we examined some of the factors that may lead to the differences in the palmitoylation levels of NMDAR complex proteins in the frontal cortex of aged animals. The Morris water maze was used to test spatial learning in 3- and 24-month-old mice. The acyl-biotinyl exchange method was used to precipitate palmitoylated proteins from the frontal cortices and hippocampi of the mice. Additionally, brain lysates from old and young mice were probed for the expression of fatty acid transporter proteins. An age-related increase of palmitoylated GluN2A, GluN2B, Fyn, PSD-95, and APT1 (acyl protein thioesterase 1) in the frontal cortex was associated with poorer reference memory and/or executive functions. These data suggest that there may be a perturbation in the palmitoylation cycle in the frontal cortex of aged mice that contributes to age-related cognitive declines.
MeSH term(s)	Aging/metabolism ; Aging/psychology ; Animals ; Cognitive Dysfunction/metabolism ; Executive Function/physiology ; Frontal Lobe/metabolism ; Lipoylation ; Male ; Maze Learning/physiology ; Memory/physiology ; Mice, Inbred C57BL ; Receptors, N-Methyl-D-Aspartate/metabolism
Chemical Substances	Receptors, N-Methyl-D-Aspartate
Language	English
Publishing date	2019-02-07
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2800598-3
ISSN	2373-2822 ; 2373-2822
ISSN (online)	2373-2822
ISSN	2373-2822
DOI	10.1523/ENEURO.0310-18.2019
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Article ; Online: Age-related differences in brain activations during spatial memory formation in a well-learned virtual Morris water maze (vMWM) task.

Reynolds, Nadjalisse C / Zhong, Jimmy Y / Clendinen, Cherita A / Moffat, Scott D / Magnusson, Kathy R

NeuroImage

2019 Volume 202, Page(s) 116069

Abstract: The current study applied a rodent-based virtual Morris water maze (vMWM) protocol to an investigation of differences in search performance and brain activations between young and older male human adults. All participants completed in-lab practice and ... ...

Abstract	The current study applied a rodent-based virtual Morris water maze (vMWM) protocol to an investigation of differences in search performance and brain activations between young and older male human adults. All participants completed in-lab practice and testing before performing the task in the fMRI scanner. Behavioral performance during fMRI scanning - measured in terms of corrected cumulative proximity (CCProx) to the goal - showed that a subgroup of older good performers attained comparable levels of search accuracy to the young while another subgroup of older poor performers exhibited consistently lower levels of search accuracy than both older good performers and the young. With regard to brain activations, young adults exhibited greater activations in the cerebellum and cuneus than all older adults, as well as older poor performers. Older good performers exhibited higher activation than older poor performers in the orbitofrontal cortex (BA 10/11), as well as in the cuneus and cerebellum. Brain-behavior correlations further showed that activations in regions involved in visuomotor control (cerebellum, lingual gyrus) and egocentric spatial processing (premotor cortex, precuneus) correlated positively with search accuracy (i.e., closer proximity to goal) in all participants. Notably, activations in the anterior hippocampus correlated positively with search accuracy (CCProx inversed) in the young but not in the old. Taken together, these findings implicated the orbitofrontal cortex and the cerebellum as playing crucial roles in executive and visuospatial processing in older adults, supporting the proposal of an age-related compensatory shift in spatial memory functions away from the hippocampus toward the prefrontal cortex.
MeSH term(s)	Adolescent ; Adult ; Age Factors ; Aged ; Aging/physiology ; Brain/physiology ; Humans ; Magnetic Resonance Imaging ; Male ; Maze Learning/physiology ; Middle Aged ; Spatial Memory/physiology ; Young Adult
Language	English
Publishing date	2019-08-02
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1147767-2
ISSN	1095-9572 ; 1053-8119
ISSN (online)	1095-9572
ISSN	1053-8119
DOI	10.1016/j.neuroimage.2019.116069
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Zs.A 3664: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 7: Show issues

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Article ; Online: Changes in expression of splice cassettes of NMDA receptor GluN1 subunits within the frontal lobe and memory in mice during aging.

Das, Siba R / Magnusson, Kathy R

Behavioural brain research

2011 Volume 222, Issue 1, Page(s) 122–133

Abstract: Age-related decline in memory has been associated with changes in mRNA and protein expression of different NMDA receptor subunits. The NMDA receptor GluN1 subunit appears to be necessary and sufficient for receptor function. There is evidence that the ... ...

Abstract	Age-related decline in memory has been associated with changes in mRNA and protein expression of different NMDA receptor subunits. The NMDA receptor GluN1 subunit appears to be necessary and sufficient for receptor function. There is evidence that the mRNA expressions of some splice forms of the subunit are influenced by aging and/or behavioral testing experience in old mice. The present study explored the relationships between behavioral testing experience and protein expression of different GluN1 subunit isoforms in the prefrontal/frontal cortex of the brain during aging. Aged C57BL/6 mice with behavioral testing experience showed declines in performance in both spatial working and reference memory tasks. Protein expression of GluN1 C-terminal cassettes C2 and C2', but not the C1 or N1 cassettes, was observed to decline with increasing age, regardless of experience. In middle-age animals, higher expressions of the GluN1 subunit and C2' cassette proteins were associated with good reference memory on initial search. Aged animals with a higher protein expression of GluN1 subunits containing C1 cassettes and the whole population of GluN1 subunits exhibited a closer proximity to the former platform location within the final phase of probe trials. However, the old mice with high expression of the C1 cassette did not show an accurate search during this phase. The old mice with lower expression of the C1 cassette protein more closely mimicked the performances of the young and middle-aged mice. These results indicate that there was heterogeneity in the effect of aging on the expression of the GluN1 subunits containing different splice cassettes. It also suggests that the GluN1 subunit might be most important for good reference memory during middle age, but this relationship may not be maintained into old age.
MeSH term(s)	Age Factors ; Aging/physiology ; Animals ; Behavior, Animal ; Cues ; Frontal Lobe/metabolism ; Gene Expression Regulation/physiology ; Male ; Maze Learning/physiology ; Memory/classification ; Memory/physiology ; Mice ; Mice, Inbred C57BL ; Protein Isoforms/metabolism ; Receptors, N-Methyl-D-Aspartate/genetics ; Receptors, N-Methyl-D-Aspartate/metabolism ; Space Perception/physiology ; Time Factors
Chemical Substances	NR1 NMDA receptor ; Protein Isoforms ; Receptors, N-Methyl-D-Aspartate
Language	English
Publishing date	2011-04-02
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	449927-x
ISSN	1872-7549 ; 0166-4328
ISSN (online)	1872-7549
ISSN	0166-4328
DOI	10.1016/j.bbr.2011.03.045
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Zs.A 1599: Show issues

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Article ; Online: Effects of ibuprofen on cognition and NMDA receptor subunit expression across aging.

Márquez Loza, Alejandra / Elias, Valerie / Wong, Carmen P / Ho, Emily / Bermudez, Michelle / Magnusson, Kathy R

Neuroscience

2017 Volume 344, Page(s) 276–292

Abstract: Age-related declines in long- and short-term memory show relationships to decreases in N-methyl-d-aspartate (NMDA) receptor expression, which may involve inflammation. This study was designed to determine effects of an anti-inflammatory drug, ibuprofen, ... ...

Abstract	Age-related declines in long- and short-term memory show relationships to decreases in N-methyl-d-aspartate (NMDA) receptor expression, which may involve inflammation. This study was designed to determine effects of an anti-inflammatory drug, ibuprofen, on cognitive function and NMDA receptor expression across aging. Male C57BL/6 mice (ages 5, 14, 20, and 26months) were fed ibuprofen (375ppm) in NIH31 diet or diet alone for 6weeks prior to testing. Behavioral testing using the Morris water maze showed that older mice performed significantly worse than younger in spatial long-term memory, reversal, and short-term memory tasks. Ibuprofen enhanced overall performance in the short-term memory task, but this appeared to be more related to improved executive function than memory. Ibuprofen induced significant decreases over all ages in the mRNA densities for GluN2B subunit, all GluN1 splice variants, and GluN1-1 splice forms in the frontal cortex and in protein expression of GluN2A, GluN2B and GluN1 C2' cassettes in the hippocampus. GluN1-3 splice form mRNA and C2' cassette protein were significantly increased across ages in frontal lobes of ibuprofen-treated mice. Ibuprofen did not alter expression of pro-inflammatory cytokines IL-1β and TNFα, but did reduce the area of reactive astrocyte immunostaining in frontal cortex of aged mice. Enhancement in executive function showed a relationship to increased GluN1-3 mRNA and decreased gliosis. These findings suggest that inflammation may play a role in executive function declines in aged animals, but other effects of ibuprofen on NMDA receptors appeared to be unrelated to aging or inflammation.
MeSH term(s)	Aging/drug effects ; Aging/metabolism ; Aging/pathology ; Aging/psychology ; Alternative Splicing ; Animals ; Anti-Inflammatory Agents, Non-Steroidal/pharmacology ; Astrocytes/drug effects ; Astrocytes/metabolism ; Astrocytes/pathology ; Brain/drug effects ; Brain/metabolism ; Brain/pathology ; Cognition/drug effects ; Cognition/physiology ; Cytokines/metabolism ; Executive Function/drug effects ; Executive Function/physiology ; Gliosis/drug therapy ; Gliosis/metabolism ; Gliosis/pathology ; Ibuprofen/pharmacology ; Male ; Maze Learning/drug effects ; Maze Learning/physiology ; Memory, Long-Term/drug effects ; Memory, Long-Term/physiology ; Memory, Short-Term/drug effects ; Memory, Short-Term/physiology ; Mice, Inbred C57BL ; Nootropic Agents/pharmacology ; RNA, Messenger/metabolism ; Random Allocation ; Receptors, N-Methyl-D-Aspartate/metabolism ; Spatial Memory/drug effects ; Spatial Memory/physiology ; Spleen/drug effects ; Spleen/metabolism
Chemical Substances	Anti-Inflammatory Agents, Non-Steroidal ; Cytokines ; Nootropic Agents ; RNA, Messenger ; Receptors, N-Methyl-D-Aspartate ; Ibuprofen (WK2XYI10QM)
Language	English
Publishing date	2017-01-03
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	196739-3
ISSN	1873-7544 ; 0306-4522
ISSN (online)	1873-7544
ISSN	0306-4522
DOI	10.1016/j.neuroscience.2016.12.041
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Article ; Online: Brain cellular senescence in mouse models of Alzheimer's disease.

Dorigatti, Angela O / Riordan, Ruben / Yu, Zhen / Ross, Grace / Wang, Rong / Reynolds-Lallement, Nadjalisse / Magnusson, Kathy / Galvan, Veronica / Perez, Viviana I

GeroScience

2022 Volume 44, Issue 2, Page(s) 1157–1168

Abstract: The accumulation of senescent cells contributes to aging pathologies, including neurodegenerative diseases, and its selective removal improves physiological and cognitive function in wild-type mice as well as in Alzheimer's disease (AD) models. AD models ...

Abstract	The accumulation of senescent cells contributes to aging pathologies, including neurodegenerative diseases, and its selective removal improves physiological and cognitive function in wild-type mice as well as in Alzheimer's disease (AD) models. AD models recapitulate some, but not all components of disease and do so at different rates. Whether brain cellular senescence is recapitulated in some or all AD models and whether the emergence of cellular senescence in AD mouse models occurs before or after the expected onset of AD-like cognitive deficits in these models are not yet known. The goal of this study was to identify mouse models of AD and AD-related dementias that develop measurable markers of cellular senescence in brain and thus may be useful to study the role of cellular senescence in these conditions. We measured the levels of cellular senescence markers in the brains of P301S(PS19), P301L, hTau, and 3xTg-AD mice that model amyloidopathy and/or tauopathy in AD and related dementias and in wild-type, age-matched control mice for each strain. Expression of cellular senescence markers in brains of transgenic P301L and 3xTg-AD mice was largely indistinguishable from that in WT control age-matched mice. In contrast, markers of cellular senescence were differentially increased in brains of transgenic hTau and P301S(PS19) mice as compared to WT control mice before the onset of AD-like cognitive deficits. Taken together, our data suggest that P301S(PS19) and hTau mice may be useful models for the study of brain cellular senescence in tauopathies including, but not limited to, AD.
MeSH term(s)	Alzheimer Disease ; Animals ; Brain/metabolism ; Cellular Senescence/physiology ; Disease Models, Animal ; Mice ; Mice, Transgenic ; Tauopathies/metabolism ; Tauopathies/pathology ; tau Proteins/genetics ; tau Proteins/metabolism
Chemical Substances	tau Proteins
Language	English
Publishing date	2022-03-06
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2886586-8
ISSN	2509-2723 ; 2509-2715
ISSN (online)	2509-2723
ISSN	2509-2715
DOI	10.1007/s11357-022-00531-5
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