mTOR and autophagy in normal brain aging and caloric restriction ameliorating age-related cognition deficits

2014 ◽  
Vol 264 ◽  
pp. 82-90 ◽  
Author(s):  
Fengying Yang ◽  
Xiaolei Chu ◽  
Miaomiao Yin ◽  
Xiaolei Liu ◽  
Hairui Yuan ◽  
...  
Keyword(s):  
Caloric Restriction ◽  
Brain Aging ◽  
Normal Brain ◽  
Age Related

scholarly journals Caloric restriction mitigates age-associated hippocampal differential CG and non-CG methylation

2017 ◽  
Author(s):  
Niran Hadad ◽  
Archana Unnikrishnan ◽  
Jordan A. Jackson ◽  
Dustin R. Masser ◽  
Laura Otalora ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Caloric Restriction ◽  
Brain Aging ◽  
Regulatory Element ◽  
Memory Function ◽  
Promoter Hypermethylation ◽  
Epigenetic Mechanism ◽  
Neuroprotective Effects ◽  
Beneficial Effects ◽  
Age Related

AbstractBrain aging is marked by cognitive decline and susceptibility to neurodegeneration. Caloric-restriction (CR) increases neurogenesis, improves memory function, and protects from age-associated neurological disorders. Epigenetic mechanisms, including DNA methylation, are vital to normal CNS cellular and memory functions, and are dysregulated with aging. The beneficial effects of CR have been proposed to work through epigenetic processes, but this is largely unexplored. We therefore tested whether life-long CR prevents age-related DNA methylation changes in the brain. Hippocampal DNA from young (3 months) and old (24 months) male mice fed ad libitum and 24 month old mice fed a 40% calorierestricted diet from 3 months of age were examined by genome-wide bisulfite sequencing to measure methylation with base-specificity. Over 27 million CG and CH (non-CG) sites were examined. Of the ~40,000 differentially methylated CGs (dmCGs) and ~80,000 CHs (dmCHs) with aging, >1/3 were prevented by CR and were found across genomic regulatory regions and gene pathways. CR also caused alterations to CG and CH methylation at sites not differentially methylated with aging, and these CR-specific changes demonstrated a different pattern of regulatory element and gene pathway enrichment than those affected by aging. CR-specific DNMT1 and TET3 promoter hypermethylation corresponded to reduced gene expression. These findings demonstrate that CR attenuates age-related CG and CH hippocampal methylation changes, in combination with CR-specific methylation that may also contribute to the neuroprotective effects of CR. The prevention of age-related methylation alterations is also consistent with the pro-longevity effects of CR working through an epigenetic mechanism.

Macrosialin increases during normal brain aging are attenuated by caloric restriction

2005 ◽  
Vol 390 (2) ◽  
pp. 76-80 ◽  
Author(s):  
Angela M. Wong ◽  
Nilay V. Patel ◽  
Nimesh K. Patel ◽  
Min Wei ◽  
Todd E. Morgan ◽  
...  
Keyword(s):  
Caloric Restriction ◽  
Brain Aging ◽  
Normal Brain

scholarly journals Changes in the intracranial volume from early adulthood to the sixth decade of life: A longitudinal study

2019 ◽  
Author(s):  
Yaron Caspi ◽  
Rachel M. Brouwer ◽  
Hugo G. Schnack ◽  
Marieke E. van de Nieuwenhuijzen ◽  
Wiepke Cahn ◽  
...  
Keyword(s):  
Mixed Model ◽  
Linear Mixed Model ◽  
Brain Aging ◽  
Age Groups ◽  
Direct Calculation ◽  
Normal Brain ◽  
Intracranial Volume ◽  
Cross Sectional ◽  
Age Related ◽  
Fourth Decade

AbstractNormal brain-aging occurs at all structural levels. Excessive pathophysiological changes in the brain, beyond the normal one, are implicated in the etiology of brain disorders such as severe forms of the schizophrenia spectrum and dementia. To account for brain-aging in health and disease, it is critical to study the age-dependent trajectories of brain biomarkers at various levels and among different age groups.The intracranial volume (ICV) is a key biological marker, and changes in the ICV during the lifespan can teach us about the biology of development, aging, and gene X environment interactions. However, whether ICV changes with age in adulthood is not resolved.Applying a semi-automatic in-house-built algorithm for ICV extraction on T1w MR brain scans in the Dutch longitudinal cohort (GROUP), we measured ICV changes. Individuals between the ages of 16 and 55 years were scanned up to three consecutive times with 3.32±0.32 years between consecutive scans (N=482, 359, 302). Using the extracted ICVs, we calculated ICV longitudinal aging-trajectories based on three analysis methods; direct calculation of ICV differences between the first and the last scan, fitting all ICV measurements of individuals to a straight line and applying a global linear mixed model fitting. We report statistically significant increases in the ICV in adulthood until the fourth decade of life (average change +0.03%/y, or about 0.5 ml/y, at age 20), and decreases in the ICV afterward (−0.09%/y, or about −1.2 ml/y, at age 55). To account for previous cross-sectional reports of ICV changes, we analyzed the same data using a cross-sectional approach. Our cross-sectional analysis detected ICV changes consistent with the previously reported cross-sectional effect. However, the reported amount of cross-sectional changes within this age range was significantly larger than the longitudinal changes. We attribute the cross-sectional results to a generational effect.In conclusion, the human intracranial volume does not stay constant during adulthood but instead shows a small increase during young adulthood and a decrease thereafter from the fourth decade of life. The age-related changes in the longitudinal setup are smaller than those reported using cross-sectional approaches and unlikely to affect structural brain imaging studies correcting for intracranial volume considerably. As to the possible mechanisms involved, this awaits further study, although thickening of the meninges and skull bones have been proposed, as well as a smaller amount of brain fluids addition above the overall loss of brain tissue.

scholarly journals Proportional Changes in Cognitive Subdomains During Normal Brain Aging

2021 ◽  
Vol 13 ◽  
Author(s):  
Yauhen Statsenko ◽  
Tetiana Habuza ◽  
Klaus Neidl-Van Gorkom ◽  
Nazar Zaki ◽  
Taleb M. Almansoori ◽  
...  
Keyword(s):  
Cognitive Functions ◽  
Brain Aging ◽  
Age Groups ◽  
Normal Brain ◽  
Similar Distribution ◽  
Information Processing Speed ◽  
Cognitive Changes ◽  
Age Related ◽  
Midlife Adults ◽  
Age Related Changes

Background: Neuroscience lacks a reliable method of screening the early stages of dementia.Objective: To improve the diagnostics of age-related cognitive functions by developing insight into the proportionality of age-related changes in cognitive subdomains.Materials and Methods: We composed a battery of psychophysiological tests and collected an open-access psychophysiological outcomes of brain atrophy (POBA) dataset by testing individuals without dementia. To extend the utility of machine learning (ML) classification in cognitive studies, we proposed estimates of the disproportional changes in cognitive functions: an index of simple reaction time to decision-making time (ISD), ISD with the accuracy performance (ISDA), and an index of performance in simple and complex visual-motor reaction with account for accuracy (ISCA). Studying the distribution of the values of the indices over age allowed us to verify whether diverse cognitive functions decline equally throughout life or there is a divergence in age-related cognitive changes.Results: Unsupervised ML clustering shows that the optimal number of homogeneous age groups is four. The sample is segregated into the following age-groups: Adolescents ∈ [0, 20), Young adults ∈ [20, 40), Midlife adults ∈ [40, 60) and Older adults ≥60 year of age. For ISD, ISDA, and ISCA values, only the median of the Adolescents group is different from that of the other three age-groups sharing a similar distribution pattern (p > 0.01). After neurodevelopment and maturation, the indices preserve almost constant values with a slight trend toward functional decline. The reaction to a moving object (RMO) test results (RMO_mean) follow another tendency. The Midlife adults group's median significantly differs from the remaining three age subsamples (p < 0.01). No general trend in age-related changes of this dependent variable is observed. For all the data (ISD, ISDA, ISCA, and RMO_mean), Levene's test reveals no significant changes of the variances in age-groups (p > 0.05). Homoscedasticity also supports our assumption about a linear dependency between the observed features and age.Conclusion: In healthy brain aging, there are proportional age-related changes in the time estimates of information processing speed and inhibitory control in task switching. Future studies should test patients with dementia to determine whether the changes of the aforementioned indicators follow different patterns.

scholarly journals DNA methylation differs extensively between strains of the same geographical origin and changes with age in Daphnia magna

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Jack Hearn ◽  
Fiona Plenderleith ◽  
Tom J. Little
Keyword(s):  
Dna Methylation ◽  
Caloric Restriction ◽  
Daphnia Magna ◽  
Single Gene ◽  
Methylation Status ◽  
Strain Differences ◽  
Life History Trait ◽  
Food Level ◽  
Epigenetic Clock ◽  
Age Related

Abstract Background Patterns of methylation influence lifespan, but methylation and lifespan may also depend on diet, or differ between genotypes. Prior to this study, interactions between diet and genotype have not been explored together to determine their influence on methylation. The invertebrate Daphnia magna is an excellent choice for testing the epigenetic response to the environment: parthenogenetic offspring are identical to their siblings (making for powerful genetic comparisons), they are relatively short lived and have well-characterised inter-strain life-history trait differences. We performed a survival analysis in response to caloric restriction and then undertook a 47-replicate experiment testing the DNA methylation response to ageing and caloric restriction of two strains of D. magna. Results Methylated cytosines (CpGs) were most prevalent in exons two to five of gene bodies. One strain exhibited a significantly increased lifespan in response to caloric restriction, but there was no effect of food-level CpG methylation status. Inter-strain differences dominated the methylation experiment with over 15,000 differently methylated CpGs. One gene, Me31b, was hypermethylated extensively in one strain and is a key regulator of embryonic expression. Sixty-one CpGs were differentially methylated between young and old individuals, including multiple CpGs within the histone H3 gene, which were hypermethylated in old individuals. Across all age-related CpGs, we identified a set that are highly correlated with chronological age. Conclusions Methylated cytosines are concentrated in early exons of gene sequences indicative of a directed, non-random, process despite the low overall DNA methylation percentage in this species. We identify no effect of caloric restriction on DNA methylation, contrary to our previous results, and established impacts of caloric restriction on phenotype and gene expression. We propose our approach here is more robust in invertebrates given genome-wide CpG distributions. For both strain and ageing, a single gene emerges as differentially methylated that for each factor could have widespread phenotypic effects. Our data showed the potential for an epigenetic clock at a subset of age positions, which is exciting but requires confirmation.

scholarly journals Contribution of TMS and TMS-EEG to the Understanding of Mechanisms Underlying Physiological Brain Aging

2021 ◽  
Vol 11 (3) ◽  
pp. 405
Author(s):  
Andrea Guerra ◽  
Lorenzo Rocchi ◽  
Alberto Grego ◽  
Francesca Berardi ◽  
Concetta Luisi ◽  
...  
Keyword(s):  
Evoked Potentials ◽  
Brain Aging ◽  
Cortical Excitability ◽  
Motor Evoked Potentials ◽  
Neurological Diseases ◽  
Physiological Activity ◽  
Neuronal Loss ◽  
Normal Brain ◽  
Potential Contribution ◽  
Brain Degeneration

In the human brain, aging is characterized by progressive neuronal loss, leading to disruption of synapses and to a degree of failure in neurotransmission. However, there is increasing evidence to support the notion that the aged brain has a remarkable ability to reorganize itself, with the aim of preserving its physiological activity. It is important to develop objective markers able to characterize the biological processes underlying brain aging in the intact human, and to distinguish them from brain degeneration associated with many neurological diseases. Transcranial magnetic stimulation (TMS), coupled with electromyography or electroencephalography (EEG), is particularly suited to this aim, due to the functional nature of the information provided, and thanks to the ease with which it can be integrated with behavioral manipulation. In this review, we aimed to provide up to date information about the role of TMS and TMS-EEG in the investigation of brain aging. In particular, we focused on data about cortical excitability, connectivity and plasticity, obtained by using readouts such as motor evoked potentials and transcranial evoked potentials. Overall, findings in the literature support an important potential contribution of TMS to the understanding of the mechanisms underlying normal brain aging. Further studies are needed to expand the current body of information and to assess the applicability of TMS findings in the clinical setting.

PET imaging of neural activity, β-amyloid, and tau in normal brain aging

2021 ◽  
Author(s):  
Kai Zhang ◽  
Hiroshi Mizuma ◽  
Xiaohui Zhang ◽  
Kayo Takahashi ◽  
Chentao Jin ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Neural Activity ◽  
Brain Aging ◽  
Normal Brain ◽  
Β Amyloid

scholarly journals Loss-of-function of p53 isoform Δ113p53 accelerates brain aging in zebrafish

2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Ting Zhao ◽  
Shengfan Ye ◽  
Zimu Tang ◽  
Liwei Guo ◽  
Zhipeng Ma ◽  
...  
Keyword(s):  
Replicative Senescence ◽  
Brain Aging ◽  
Ventricular Zone ◽  
Human Fibroblasts ◽  
Cell Lineage ◽  
Lineage Tracing ◽  
Dependent Manner ◽  
Loss Of Function ◽  
Antioxidant Genes ◽  
Age Related

AbstractReactive oxygen species (ROS) stress has been demonstrated as potentially critical for induction and maintenance of cellular senescence, and been considered as a contributing factor in aging and in various neurological disorders including Alzheimer’s disease (AD) and amyotrophic lateral sclerosis (ALS). In response to low-level ROS stress, the expression of Δ133p53, a human p53 isoform, is upregulated to promote cell survival and protect cells from senescence by enhancing the expression of antioxidant genes. In normal conditions, the basal expression of Δ133p53 prevents human fibroblasts, T lymphocytes, and astrocytes from replicative senescence. It has been also found that brain tissues from AD and ALS patients showed decreased Δ133p53 expression. However, it is uncharacterized if Δ133p53 plays a role in brain aging. Here, we report that zebrafish Δ113p53, an ortholog of human Δ133p53, mainly expressed in some of the radial glial cells along the telencephalon ventricular zone in a full-length p53-dependent manner. EDU-labeling and cell lineage tracing showed that Δ113p53-positive cells underwent cell proliferation to contribute to the neuron renewal process. Importantly, Δ113p53M/M mutant telencephalon possessed less proliferation cells and more senescent cells compared to wild-type (WT) zebrafish telencephalon since 9-months old, which was associated with decreased antioxidant genes expression and increased level of ROS in the mutant telencephalon. More interestingly, unlike the mutant fish at 5-months old with cognition ability, Δ113p53M/M zebrafish, but not WT zebrafish, lost their learning and memory ability at 19-months old. The results demonstrate that Δ113p53 protects the brain from aging by its antioxidant function. Our finding provides evidence at the organism level to show that depletion of Δ113p53/Δ133p53 may result in long-term ROS stress, and finally lead to age-related diseases, such as AD and ALS in humans.

scholarly journals Aging-associated deficit in CCR7 is linked to worsened glymphatic function, cognition, neuroinflammation, and β-amyloid pathology

2021 ◽  
Vol 7 (21) ◽  
pp. eabe4601
Author(s):  
Sandro Da Mesquita ◽  
Jasmin Herz ◽  
Morgan Wall ◽  
Taitea Dykstra ◽  
Kalil Alves de Lima ◽  
...  
Keyword(s):  
T Cells ◽  
Cognitive Decline ◽  
Brain Aging ◽  
Therapeutic Potential ◽  
T Cell Response ◽  
Age Related ◽  
Lymphatic Vasculature ◽  
Amyloid Aβ ◽  
Β Amyloid ◽  
Old Mice

Aging leads to a progressive deterioration of meningeal lymphatics and peripheral immunity, which may accelerate cognitive decline. We hypothesized that an age-related reduction in C-C chemokine receptor type 7 (CCR7)–dependent egress of immune cells through the lymphatic vasculature mediates some aspects of brain aging and potentially exacerbates cognitive decline and Alzheimer’s disease–like brain β-amyloid (Aβ) pathology. We report a reduction in CCR7 expression by meningeal T cells in old mice that is linked to increased effector and regulatory T cells. Hematopoietic CCR7 deficiency mimicked the aging-associated changes in meningeal T cells and led to reduced glymphatic influx and cognitive impairment. Deletion of CCR7 in 5xFAD transgenic mice resulted in deleterious neurovascular and microglial activation, along with increased Aβ deposition in the brain. Treating old mice with anti-CD25 antibodies alleviated the exacerbated meningeal regulatory T cell response and improved cognitive function, highlighting the therapeutic potential of modulating meningeal immunity to fine-tune brain function in aging and in neurodegenerative diseases.

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