Pub Date : 2023-12-23DOI: 10.1016/j.nbas.2023.100104
Camila Leite Santos , Larissa Daniele Bobermin , André Quincozes-Santos
The aging process induces neurochemical alterations in different brain regions, including hypothalamus. This pivotal area of the central nervous system (CNS) is crucial for detection and integration of nutritional and hormonal signals from the periphery of the body to maintain metabolic homeostasis. Astrocytes support the CNS homeostasis, energy metabolism, and inflammatory response, as well as increasing evidence has highlighted a critical role of astrocytes in orchestrating hypothalamic functions and in gliocrine system. In this study, we aimed to investigate the age-dependent mRNA expression of adenosine receptors, the insulin-like growth factor 1 receptor (IGF1R), and the hypoxia-inducible factor 1α (HIF1α), in addition to the levels of IGF1 and HIF1α in hypothalamic astrocyte cultures derived from newborn, adult, and aged rats. Our results revealed age-dependent changes in adenosine receptors, as well as a decrease in IGF1R/IGF1 and HIF1α. Of note, adenosine receptors, IGF1, and HIF1α are affected by inflammatory, redox, and metabolic processes, which can remodel hypothalamic properties, as observed in aging brain, reinforcing the role of hypothalamic astrocytes as targets for understanding the onset and/or progression of age-related diseases.
{"title":"Aging changes the expression of adenosine receptors, insulin-like growth factor 1 (IGF1), and hypoxia-inducible factor 1α (HIF1α) in hypothalamic astrocyte cultures","authors":"Camila Leite Santos , Larissa Daniele Bobermin , André Quincozes-Santos","doi":"10.1016/j.nbas.2023.100104","DOIUrl":"https://doi.org/10.1016/j.nbas.2023.100104","url":null,"abstract":"<div><p>The aging process induces neurochemical alterations in different brain regions, including hypothalamus. This pivotal area of the central nervous system (CNS) is crucial for detection and integration of nutritional and hormonal signals from the periphery of the body to maintain metabolic homeostasis. Astrocytes support the CNS homeostasis, energy metabolism, and inflammatory response, as well as increasing evidence has highlighted a critical role of astrocytes in orchestrating hypothalamic functions and in gliocrine system. In this study, we aimed to investigate the age-dependent mRNA expression of adenosine receptors, the insulin-like growth factor 1 receptor (IGF1R), and the hypoxia-inducible factor 1α (HIF1α), in addition to the levels of IGF1 and HIF1α in hypothalamic astrocyte cultures derived from newborn, adult, and aged rats. Our results revealed age-dependent changes in adenosine receptors, as well as a decrease in IGF1R/IGF1 and HIF1α. Of note, adenosine receptors, IGF1, and HIF1α are affected by inflammatory, redox, and metabolic processes, which can remodel hypothalamic properties, as observed in aging brain, reinforcing the role of hypothalamic astrocytes as targets for understanding the onset and/or progression of age-related diseases.</p></div>","PeriodicalId":72131,"journal":{"name":"Aging brain","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2589958923000415/pdfft?md5=f897cae43f9c5c8b59df8005b4f6833c&pid=1-s2.0-S2589958923000415-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139033820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-07DOI: 10.1016/j.nbas.2023.100103
Ylva Köhncke , Simone Kühn , Sandra Düzel , Myriam C. Sander , Andreas M. Brandmaier , Ulman Lindenberger
According to the maintenance hypothesis (Nyberg et al., 2012), structural integrity of the brain’s grey matter helps to preserve cognitive functioning into old age. A corollary of this hypothesis that can be tested in cross-sectional data is that grey-matter structural integrity and general cognitive ability are positively associated in old age. Building on Köhncke et al. (2021), who found that region-specific latent factors of grey-matter integrity are positively associated with episodic memory ability among older adults, we examine associations between general factors of grey-matter integrity and a general factor of cognitive ability in a cross-sectional sample of 1466 participants aged 60–88 years, 319 of whom contributed imaging data. Indicator variables based on T1-weighted images (voxel-based morphometry, VBM), magnetization-transfer imaging (MT), and diffusion tensor imaging-derived mean diffusivity (MD) had sufficient portions of variance in common to establish latent factors of grey-matter structure for a comprehensive set of regions of interest (ROI). Individual differences in grey-matter factors were positively correlated across neocortical and limbic areas, allowing for the definition of second-order, general factors for neocortical and limbic ROI, respectively. Both general grey-matter factors were positively correlated with general cognitive ability. For the basal ganglia, the three modality-specific indicators showed heterogenous loading patterns, and no reliable associations of the general grey-matter factor to general cognitive ability were found. To provide more direct tests of the maintenance hypothesis, we recommend applying the present structural modeling approach to longitudinal data, thereby enhancing the physiological validity of latent constructs of brain structure.
{"title":"Grey-matter structure in cortical and limbic regions correlates with general cognitive ability in old age","authors":"Ylva Köhncke , Simone Kühn , Sandra Düzel , Myriam C. Sander , Andreas M. Brandmaier , Ulman Lindenberger","doi":"10.1016/j.nbas.2023.100103","DOIUrl":"10.1016/j.nbas.2023.100103","url":null,"abstract":"<div><p>According to the maintenance hypothesis (Nyberg et al., 2012), structural integrity of the brain’s grey matter helps to preserve cognitive functioning into old age. A corollary of this hypothesis that can be tested in cross-sectional data is that grey-matter structural integrity and general cognitive ability are positively associated in old age. Building on Köhncke et al. (2021), who found that region-specific latent factors of grey-matter integrity are positively associated with episodic memory ability among older adults, we examine associations between general factors of grey-matter integrity and a general factor of cognitive ability in a cross-sectional sample of 1466 participants aged 60–88 years, 319 of whom contributed imaging data. Indicator variables based on T1-weighted images (voxel-based morphometry, VBM), magnetization-transfer imaging (MT), and diffusion tensor imaging-derived mean diffusivity (MD) had sufficient portions of variance in common to establish latent factors of grey-matter structure for a comprehensive set of regions of interest (ROI). Individual differences in grey-matter factors were positively correlated across neocortical and limbic areas, allowing for the definition of second-order, general factors for neocortical and limbic ROI, respectively. Both general grey-matter factors were positively correlated with general cognitive ability. For the basal ganglia, the three modality-specific indicators showed heterogenous loading patterns, and no reliable associations of the general grey-matter factor to general cognitive ability were found. To provide more direct tests of the maintenance hypothesis, we recommend applying the present structural modeling approach to longitudinal data, thereby enhancing the physiological validity of latent constructs of brain structure.</p></div>","PeriodicalId":72131,"journal":{"name":"Aging brain","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2589958923000403/pdfft?md5=46899d9fa369da5b9c325e455852af3b&pid=1-s2.0-S2589958923000403-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138625743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-07-07eCollection Date: 2023-01-01DOI: 10.1016/j.nbas.2023.100083
Susanne M Jaeggi, Alexandria N Weaver, Elena Carbone, Francesca E Trane, Rachel N Smith-Peirce, Martin Buschkuehl, Christoph Flueckiger, Madison Carlson, John Jonides, Erika Borella
Working Memory (WM) training has shown promise in supporting cognitive functioning in older adult populations, but effects that generalize beyond the trained task have been inconsistent. Targeting cognitive processes in isolation might be a limiting factor given that metacognitive and motivational factors have been shown to impact older adults' engagement with challenging cognitive activities, such as WM training. The current feasibility study implemented a novel metacognitive intervention in conjunction with WM training in older adults and examined its potential amplifying short- and long-term effects on cognitive and self-report outcomes as compared to WM or active control training alone. One-hundred and nineteen older adults completed a cognitive training over the course of 20 sessions at home. The cognitive training targeted either WM or general knowledge. In addition, one of the WM training groups completed a metacognitive program via group seminars. We tested for group differences in WM, inhibitory control, and episodic memory, and we assessed participants' perceived self-efficacy and everyday memory failures. At post-test, we replicated earlier work by demonstrating that participants who completed the WM intervention outperformed the active control group in non-trained WM measures, and to some extent, in inhibitory control. However, we found no evidence that the supplemental metacognitive program led to benefits over and above the WM intervention. Nonetheless, we conclude that our metacognitive program is a step in the right direction given the tentative long-term effects and participants' positive feedback, but more longitudinal data with larger sample sizes are needed to confirm these early findings.
{"title":"EngAge - A metacognitive intervention to supplement working memory training: A feasibility study in older adults.","authors":"Susanne M Jaeggi, Alexandria N Weaver, Elena Carbone, Francesca E Trane, Rachel N Smith-Peirce, Martin Buschkuehl, Christoph Flueckiger, Madison Carlson, John Jonides, Erika Borella","doi":"10.1016/j.nbas.2023.100083","DOIUrl":"10.1016/j.nbas.2023.100083","url":null,"abstract":"<p><p>Working Memory (WM) training has shown promise in supporting cognitive functioning in older adult populations, but effects that generalize beyond the trained task have been inconsistent. Targeting cognitive processes in isolation might be a limiting factor given that metacognitive and motivational factors have been shown to impact older adults' engagement with challenging cognitive activities, such as WM training. The current feasibility study implemented a novel metacognitive intervention in conjunction with WM training in older adults and examined its potential amplifying short- and long-term effects on cognitive and self-report outcomes as compared to WM or active control training alone. One-hundred and nineteen older adults completed a cognitive training over the course of 20 sessions at home. The cognitive training targeted either WM or general knowledge. In addition, one of the WM training groups completed a metacognitive program via group seminars. We tested for group differences in WM, inhibitory control, and episodic memory, and we assessed participants' perceived self-efficacy and everyday memory failures. At post-test, we replicated earlier work by demonstrating that participants who completed the WM intervention outperformed the active control group in non-trained WM measures, and to some extent, in inhibitory control. However, we found no evidence that the supplemental metacognitive program led to benefits over and above the WM intervention. Nonetheless, we conclude that our metacognitive program is a step in the right direction given the tentative long-term effects and participants' positive feedback, but more longitudinal data with larger sample sizes are needed to confirm these early findings.</p>","PeriodicalId":72131,"journal":{"name":"Aging brain","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10719574/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54909180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.1016/j.nbas.2022.100060
Josef Zihl , Simone Reppermund
Cognitive decline as part of mental ageing is typically assessed with standardized tests; below-average performance in such tests is used as an indicator for pathological cognitive aging. In addition, morphological and functional changes in the brain are used as parameters for age-related pathological decline in cognitive abilities. However, there is no simple link between the trajectories of changes in cognition and morphological or functional changes in the brain. Furthermore, below-average test performance does not necessarily mean a significant impairment in everyday activities. It therefore appears crucial to record individual everyday tasks and their cognitive (and other) requirements in functional terms. This would also allow reliable assessment of the ecological validity of existing and insufficient cognitive skills. Understanding and dealing with the phenomena and consequences of mental aging does of course not only depend on cognition. Motivation and emotions as well personal meaning of life and life satisfaction play an equally important role. This means, however, that cognition represents only one, albeit important, aspect of mental aging. Furthermore, creating and development of proper assessment tools for functional cognition is important. In this contribution we would like to discuss some aspects that we consider relevant for a holistic view of the aging mind and promote a strengthening of a multidisciplinary approach with close cooperation between all basic and applied sciences involved in aging research, a quick translation of the research results into practice, and a close cooperation between all disciplines and professions who advise and support older people.
{"title":"The aging mind: A complex challenge for research and practice","authors":"Josef Zihl , Simone Reppermund","doi":"10.1016/j.nbas.2022.100060","DOIUrl":"10.1016/j.nbas.2022.100060","url":null,"abstract":"<div><p>Cognitive decline as part of mental ageing is typically assessed with standardized tests; below-average performance in such tests is used as an indicator for pathological cognitive aging. In addition, morphological and functional changes in the brain are used as parameters for age-related pathological decline in cognitive abilities. However, there is no simple link between the trajectories of changes in cognition and morphological or functional changes in the brain. Furthermore, below-average test performance does not necessarily mean a significant impairment in everyday activities. It therefore appears crucial to record individual everyday tasks and their cognitive (and other) requirements in functional terms. This would also allow reliable assessment of the ecological validity of existing and insufficient cognitive skills. Understanding and dealing with the phenomena and consequences of mental aging does of course not only depend on cognition. Motivation and emotions as well personal meaning of life and life satisfaction play an equally important role. This means, however, that cognition represents only one, albeit important, aspect of mental aging. Furthermore, creating and development of proper assessment tools for functional cognition is important. In this contribution we would like to discuss some aspects that we consider relevant for a holistic view of the aging mind and promote a strengthening of a multidisciplinary approach with close cooperation between all basic and applied sciences involved in aging research, a quick translation of the research results into practice, and a close cooperation between all disciplines and professions who advise and support older people.</p></div>","PeriodicalId":72131,"journal":{"name":"Aging brain","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1d/75/main.PMC9997127.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9101408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.1016/j.nbas.2023.100069
Sadashiva K. Pai
{"title":"Role of mitochondria in α-synuclein mediated neuronal toxicity","authors":"Sadashiva K. Pai","doi":"10.1016/j.nbas.2023.100069","DOIUrl":"10.1016/j.nbas.2023.100069","url":null,"abstract":"","PeriodicalId":72131,"journal":{"name":"Aging brain","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/19/26/main.PMC10318298.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9794849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.1016/j.nbas.2023.100092
Janice X. Li , Hannah L. Nguyen , Tianchen Qian , Davis C. Woodworth , S. Ahmad Sajjadi , for the Alzheimer's Disease Neuroimaging Initiative
Hippocampal sclerosis of aging (HS-A) is a common degenerative neuropathology in older individuals and is associated with dementia. HS-A is characterized by disproportionate hippocampal atrophy at autopsy but cannot be diagnosed during life. Therefore, little is known about the onset and progression of hippocampal atrophy in individuals with HS-A. To better understand the onset and progression of hippocampal atrophy in HS-A, we examined longitudinal hippocampal atrophy using serial MRI in participants with HS-A at autopsy (HS-A+, n = 8) compared to participants with limbic-predominant age-related TDP-43 encephalopathy neuropathological change (LATE-NC) without HS-A (n = 13), Alzheimer’s disease neuropathologic change (ADNC) without HS-A or LATE-NC (n = 16), and those without these pathologies (n = 7). We found that participants with HS-A had lower hippocampal volumes compared to the other groups, and this atrophy preceded the onset of dementia. There was also some evidence that rates of hippocampal volume loss were slightly slower in those with HS-A. Together, these results suggest that the disproportionate hippocampal atrophy seen in HS-A may begin early prior to dementia.
{"title":"Longitudinal hippocampal atrophy in hippocampal sclerosis of aging","authors":"Janice X. Li , Hannah L. Nguyen , Tianchen Qian , Davis C. Woodworth , S. Ahmad Sajjadi , for the Alzheimer's Disease Neuroimaging Initiative","doi":"10.1016/j.nbas.2023.100092","DOIUrl":"10.1016/j.nbas.2023.100092","url":null,"abstract":"<div><p>Hippocampal sclerosis of aging (HS-A) is a common degenerative neuropathology in older individuals and is associated with dementia. HS-A is characterized by disproportionate hippocampal atrophy at autopsy but cannot be diagnosed during life. Therefore, little is known about the onset and progression of hippocampal atrophy in individuals with HS-A. To better understand the onset and progression of hippocampal atrophy in HS-A, we examined longitudinal hippocampal atrophy using serial MRI in participants with HS-A at autopsy (HS-A+, n = 8) compared to participants with limbic-predominant age-related TDP-43 encephalopathy neuropathological change (LATE-NC) without HS-A (n = 13), Alzheimer’s disease neuropathologic change (ADNC) without HS-A or LATE-NC (n = 16), and those without these pathologies (n = 7). We found that participants with HS-A had lower hippocampal volumes compared to the other groups, and this atrophy preceded the onset of dementia. There was also some evidence that rates of hippocampal volume loss were slightly slower in those with HS-A. Together, these results suggest that the disproportionate hippocampal atrophy seen in HS-A may begin early prior to dementia.</p></div>","PeriodicalId":72131,"journal":{"name":"Aging brain","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/07/17/main.PMC10448324.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10133623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.1016/j.nbas.2023.100094
Jarkko Johansson , Nina Karalija , Alireza Salami
Extant research suggest aging-related losses of different dopaminergic markers, including presynaptic dopamine transporters as well as post-synaptic DA receptors. Given the central role of DA in neurocognitive functions, maintenance of a healthy DA system may be a key to mitigate age-related cognitive decline. Mechanisms behind DA losses in aging are however largely uncharted. Past research documented an association between dopaminergic integrity and cerebrovascular health (via white matter lesion volumes). However, it remains unclear whether proximity to lesions affected the spatial patterns of age-related D1DR differences within the striatum, and whether such differences are related to mnemonic function. Here, a large cohort of middle-aged to older healthy participants (age = 40–80 years, n = 119, 50 % women) was assessed for D1-receptor (D1DR) availability with positron emission tomography using [11C]SCH23390, and for white matter lesions using FLAIR-MRI. We found evidence for variations in degree of age-related differences along the ventro-dorsal axis, with more pronounced differences in the dorsal caudate. Further analyses revealed an association between distance to lesions and extent of D1DR losses in the caudate. Furthermore, D1DR differences in dorsal caudate (proximal to lesions) was more strongly associated with memory performance. In conclusion, the present findings suggest that maintenance of cerebrovascular health may be a key factor in promoting successful dopaminergic and memory aging.
{"title":"Cerebrovascular integrity affects gradients of aging-related dopamine D1 differences in the striatum","authors":"Jarkko Johansson , Nina Karalija , Alireza Salami","doi":"10.1016/j.nbas.2023.100094","DOIUrl":"10.1016/j.nbas.2023.100094","url":null,"abstract":"<div><p>Extant research suggest aging-related losses of different dopaminergic markers, including presynaptic dopamine transporters as well as post-synaptic DA receptors. Given the central role of DA in neurocognitive functions, maintenance of a healthy DA system may be a key to mitigate age-related cognitive decline. Mechanisms behind DA losses in aging are however largely uncharted. Past research documented an association between dopaminergic integrity and cerebrovascular health (via white matter lesion volumes). However, it remains unclear whether proximity to lesions affected the spatial patterns of age-related D1DR differences within the striatum, and whether such differences are related to mnemonic function. Here, a large cohort of middle-aged to older healthy participants (age = 40–80 years, n = 119, 50 % women) was assessed for D1-receptor (D1DR) availability with positron emission tomography using [<sup>11</sup>C]SCH23390, and for white matter lesions using FLAIR-MRI. We found evidence for variations in degree of age-related differences along the ventro-dorsal axis, with more pronounced differences in the dorsal caudate. Further analyses revealed an association between distance to lesions and extent of D1DR losses in the caudate. Furthermore, D1DR differences in dorsal caudate (proximal to lesions) was more strongly associated with memory performance. In conclusion, the present findings suggest that maintenance of cerebrovascular health may be a key factor in promoting successful dopaminergic and memory aging.</p></div>","PeriodicalId":72131,"journal":{"name":"Aging brain","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e6/9d/main.PMC10460986.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10475849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.1016/j.nbas.2023.100085
Isabel J. Sible , Hyun Joo Yoo , Jungwon Min , Kaoru Nashiro , Catie Chang , Daniel A. Nation , Mara Mather
Blood pressure variability (BPV), independent of mean blood pressure levels, is associated with cerebrovascular disease burden on MRI and postmortem evaluation. However, less is known about relationships with markers of cerebrovascular dysfunction, such as diminished spontaneous brain activity as measured by the amplitude of low frequency fluctuations (ALFF), especially in brain regions with vascular and neuronal vulnerability in aging. We investigated the relationship between short-term BPV and concurrent regional ALFF from resting state fMRI in a sample of community-dwelling older adults (n = 44) and healthy younger adults (n = 49). In older adults, elevated systolic BPV was associated with lower ALFF in widespread medial temporal regions and the anterior cingulate cortex. Higher systolic BPV in younger adults was also related to lower ALFF in the medial temporal lobe, albeit in fewer subregions, and the amygdala. There were no significant associations between systolic BPV and ALFF across the right/left whole brain or in the insular cortex in either group. Findings suggest a possible regional vulnerability to cerebrovascular dysfunction and short-term fluctuations in blood pressure. BPV may be an understudied risk factor for cerebrovascular changes in aging.
{"title":"Short-term blood pressure variability is inversely related to regional amplitude of low frequency fluctuations in older and younger adults","authors":"Isabel J. Sible , Hyun Joo Yoo , Jungwon Min , Kaoru Nashiro , Catie Chang , Daniel A. Nation , Mara Mather","doi":"10.1016/j.nbas.2023.100085","DOIUrl":"10.1016/j.nbas.2023.100085","url":null,"abstract":"<div><p>Blood pressure variability (BPV), independent of mean blood pressure levels, is associated with cerebrovascular disease burden on MRI and postmortem evaluation. However, less is known about relationships with markers of cerebrovascular dysfunction, such as diminished spontaneous brain activity as measured by the amplitude of low frequency fluctuations (ALFF), especially in brain regions with vascular and neuronal vulnerability in aging. We investigated the relationship between short-term BPV and concurrent regional ALFF from resting state fMRI in a sample of community-dwelling older adults (<em>n</em> = 44) and healthy younger adults (<em>n</em> = 49). In older adults, elevated systolic BPV was associated with lower ALFF in widespread medial temporal regions and the anterior cingulate cortex. Higher systolic BPV in younger adults was also related to lower ALFF in the medial temporal lobe, albeit in fewer subregions, and the amygdala. There were no significant associations between systolic BPV and ALFF across the right/left whole brain or in the insular cortex in either group. Findings suggest a possible regional vulnerability to cerebrovascular dysfunction and short-term fluctuations in blood pressure. BPV may be an understudied risk factor for cerebrovascular changes in aging.</p></div>","PeriodicalId":72131,"journal":{"name":"Aging brain","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10362312/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9862521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.1016/j.nbas.2023.100087
K.G. Akbulut , A. Keskin-Aktan , S.A. Abgarmi , H. Akbulut
Background
Though the exact mechanisms regarding brain aging and its relation to neurodegenerative disorders are not precise, oxidative stress, the key regulators of apoptosis and autophagy, such as bcl-2 and beclin 1, seem to be the potential players in the aging of the cerebral cortex and hippocampus. As a type of nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases, sirtuin 2 (SIRT2) has been associated to age-related diseases. However, the exact role of SIRT2 in brain aging is not well studied. The objective of the current study was to study the role of SIRT2 inhibition on brain aging through the neuroprotective mechanisms.
Methods
We tested the effects of AGK-2, a SIRT2 inhibitor, on oxidative stress parameters, apoptosis and autophagy regulators including bcl-2, bax, beclin1 in young and old rats. 24 Wistar albino rats (3 months-old and 22 months-old) were divided into four groups; Young-Control (4% DMSO+PBS), Young-AGK-2 (10 µM/bw, ip), Aged-Control, and Aged-AGK-2. Following the 30 days of drug administration period the rats were sacrificed and the cerebral cortex, hippocampus, and cerebellum were isolated. Total antioxidant status (TAS) and total oxidant status (TOS) were measured as oxidative stress parameters in all three brain regions. SIRT2, bcl-2, and bax protein expression levels were measured by western blot and gene expression level of beclin 1, Atg5, and SIRT2 by real-time PCR.
Results
The bcl-2, bcl-2/bax ratio, beclin 1, and TAS in the cerebral cortex of the aged group were significantly decreased; however, the TOS, oxidative stress index (OSI), and SIRT2 expression in the cerebral cortex and hippocampus increased. SIRT2 inhibition by AGK-2 reduced TOS and OSI levels in all brain regions and increased bcl-2, bcl-2/bax ratio. In aged animals, AGK-2 also increased the beclin 1 levels in the cortex and hippocampus.
Conclusion
Our results indicate that SIRT2 has an essential role in brain aging. The inhibition of SIRT2 by AGK-2 may increase cell survival and decrease aging related processes in the cerebral cortex and hippocampus via decreasing oxidative stress, and increasing bcl-2 and beclin 1 expression.
{"title":"The role of SIRT2 inhibition on the aging process of brain in male rats","authors":"K.G. Akbulut , A. Keskin-Aktan , S.A. Abgarmi , H. Akbulut","doi":"10.1016/j.nbas.2023.100087","DOIUrl":"10.1016/j.nbas.2023.100087","url":null,"abstract":"<div><h3>Background</h3><p>Though the exact mechanisms regarding brain aging and its relation to neurodegenerative disorders are not precise, oxidative stress, the key regulators of apoptosis and autophagy, such as bcl-2 and beclin 1, seem to be the potential players in the aging of the cerebral cortex and hippocampus. As a type of nicotinamide adenine dinucleotide (NAD<sup>+</sup>)-dependent deacetylases, sirtuin 2 (SIRT2) has been associated to age-related diseases. However, the exact role of SIRT2 in brain aging is not well studied. The objective of the current study was to study the role of SIRT2 inhibition on brain aging through the neuroprotective mechanisms.</p></div><div><h3>Methods</h3><p>We tested the effects of AGK-2, a SIRT2 inhibitor, on oxidative stress parameters, apoptosis and autophagy regulators including bcl-2, bax, beclin1 in young and old rats. 24 Wistar albino rats (3 months-old and 22 months-old) were divided into four groups; Young-Control (4% DMSO+PBS), Young-AGK-2 (10 µM/bw, ip), Aged-Control, and Aged-AGK-2. Following the 30 days of drug administration period the rats were sacrificed and the cerebral cortex, hippocampus, and cerebellum were isolated. Total antioxidant status (TAS) and total oxidant status (TOS) were measured as oxidative stress parameters in all three brain regions. SIRT2, bcl-2, and bax protein expression levels were measured by western blot and gene expression level of beclin 1, Atg5, and SIRT2 by real-time PCR.</p></div><div><h3>Results</h3><p>The bcl-2, bcl-2/bax ratio, beclin 1, and TAS in the cerebral cortex of the aged group were significantly decreased; however, the TOS, oxidative stress index (OSI), and SIRT2 expression in the cerebral cortex and hippocampus increased. SIRT2 inhibition by AGK-2 reduced TOS and OSI levels in all brain regions and increased bcl-2, bcl-2/bax ratio. In aged animals, AGK-2 also increased the beclin 1 levels in the cortex and hippocampus.</p></div><div><h3>Conclusion</h3><p>Our results indicate that SIRT2 has an essential role in brain aging. The inhibition of SIRT2 by AGK-2 may increase cell survival and decrease aging related processes in the cerebral cortex and hippocampus via decreasing oxidative stress, and increasing bcl-2 and beclin 1 expression.</p></div>","PeriodicalId":72131,"journal":{"name":"Aging brain","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a0/85/main.PMC10372168.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9962795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}