scholarly journals Gut Microbiota: Critical Controller and Intervention Target in Brain Aging and Cognitive Impairment

2021 ◽  
Vol 13 ◽  
Author(s):  
Hui Li ◽  
Junjun Ni ◽  
Hong Qing
Keyword(s):  
Cognitive Impairment ◽  
Gut Microbiota ◽  
Healthy Aging ◽  
Brain Aging ◽  
Current Trend ◽  
The Body ◽  
Dietary Interventions ◽  
Age Related ◽  
Functional Features ◽  
The Brain

The current trend for the rapid growth of the global aging population poses substantial challenges for society. The human aging process has been demonstrated to be closely associated with changes in gut microbiota composition, diversity, and functional features. During the first 2 years of life, the gut microbiota undergoes dramatic changes in composition and metabolic functions as it colonizes and develops in the body. Although the gut microbiota is nearly established by the age of three, it continues to mature until adulthood, when it comprises more stable and diverse microbial species. Meanwhile, as the physiological functions of the human body deteriorated with age, which may be a result of immunosenescence and “inflammaging,” the guts of elderly people are generally characterized by an enrichment of pro-inflammatory microbes and a reduced abundance of beneficial species. The gut microbiota affects the development of the brain through a bidirectional communication system, called the brain-gut-microbiota (BGM) axis, and dysregulation of this communication is pivotal in aging-related cognitive impairment. Microbiota-targeted dietary interventions and the intake of probiotics/prebiotics can increase the abundance of beneficial species, boost host immunity, and prevent gut-related diseases. This review summarizes the age-related changes in the human gut microbiota based on recent research developments. Understanding these changes will likely facilitate the design of novel therapeutic strategies to achieve healthy aging.

scholarly journals Impairments in Brain Bioenergetics in Aging and Tau Pathology: A Chicken and Egg Situation?

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2531
Author(s):  
Amandine Grimm
Keyword(s):  
Brain Metabolism ◽  
Brain Aging ◽  
Cognitive Impairments ◽  
Tau Phosphorylation ◽  
The Body ◽  
Tau Pathology ◽  
Age Related ◽  
Energy Consuming ◽  
Effects Of Aging ◽  
The Brain

The brain is the most energy-consuming organ of the body and impairments in brain energy metabolism will affect neuronal functionality and viability. Brain aging is marked by defects in energetic metabolism. Abnormal tau protein is a hallmark of tauopathies, including Alzheimer’s disease (AD). Pathological tau was shown to induce bioenergetic impairments by affecting mitochondrial function. Although it is now clear that mutations in the tau-coding gene lead to tau pathology, the causes of abnormal tau phosphorylation and aggregation in non-familial tauopathies, such as sporadic AD, remain elusive. Strikingly, both tau pathology and brain hypometabolism correlate with cognitive impairments in AD. The aim of this review is to discuss the link between age-related decrease in brain metabolism and tau pathology. In particular, the following points will be discussed: (i) the common bioenergetic features observed during brain aging and tauopathies; (ii) how age-related bioenergetic defects affect tau pathology; (iii) the influence of lifestyle factors known to modulate brain bioenergetics on tau pathology. The findings compiled here suggest that age-related bioenergetic defects may trigger abnormal tau phosphorylation/aggregation and cognitive impairments after passing a pathological threshold. Understanding the effects of aging on brain metabolism may therefore help to identify disease-modifying strategies against tau-induced neurodegeneration.

scholarly journals Bile Acids as Key Modulators of the Brain-Gut-Microbiota Axis in Alzheimer’s Disease

2021 ◽  
pp. 1-17
Author(s):  
Agata Mulak
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gut Microbiota ◽  
Bile Acids ◽  
Microbiota Composition ◽  
Dietary Interventions ◽  
Age Related ◽  
Host Metabolism ◽  
The Brain ◽  
Gut Microbiota Composition

Recently, the concept of the brain-gut-microbiota (BGM) axis disturbances in the pathogenesis of Alzheimer’s disease (AD) has been receiving growing attention. At the same time, accumulating data revealing complex interplay between bile acids (BAs), gut microbiota, and host metabolism have shed new light on a potential impact of BAs on the BGM axis. The crosstalk between BAs and gut microbiota is based on reciprocal interactions since microbiota determines BA metabolism, while BAs affect gut microbiota composition. Secondary BAs as microbe-derived neuroactive molecules may affect each of three main routes through which interactions within the BGM axis occur including neural, immune, and neuroendocrine pathways. BAs participate in the regulation of multiple gut-derived molecule release since their receptors are expressed on various cells. The presence of BAs and their receptors in the brain implies a direct effect of BAs on the regulation of neurological functions. Experimental and clinical data confirm that disturbances in BA signaling are present in the course of AD. Disturbed ratio of primary to secondary BAs as well as alterations in BA concertation in serum and brain samples have been reported. An age-related shift in the gut microbiota composition associated with its decreased diversity and stability observed in AD patients may significantly affect BA metabolism and signaling. Given recent evidence on BA neuroprotective and anti-inflammatory effects, new therapeutic targets have been explored including gut microbiota modulation by probiotics and dietary interventions, ursodeoxycholic acid supplementation, and use of BA receptor agonists.

Longitudinal Changes in Individual BrainAGE in Healthy Aging, Mild Cognitive Impairment, and Alzheimer’s Disease

GeroPsych ◽  
2012 ◽  
Vol 25 (4) ◽  
pp. 235-245 ◽  
Author(s):  
Katja Franke ◽  
Christian Gaser
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Healthy Aging ◽  
Brain Aging ◽  
Elderly Subjects ◽  
Additional Increase ◽  
Longitudinal Changes ◽  
Novel Method ◽  
The Brain

We recently proposed a novel method that aggregates the multidimensional aging pattern across the brain to a single value. This method proved to provide stable and reliable estimates of brain aging – even across different scanners. While investigating longitudinal changes in BrainAGE in about 400 elderly subjects, we discovered that patients with Alzheimer’s disease and subjects who had converted to AD within 3 years showed accelerated brain atrophy by +6 years at baseline. An additional increase in BrainAGE accumulated to a score of about +9 years during follow-up. Accelerated brain aging was related to prospective cognitive decline and disease severity. In conclusion, the BrainAGE framework indicates discrepancies in brain aging and could thus serve as an indicator for cognitive functioning in the future.

scholarly journals A fiber-deprived diet causes cognitive impairment and hippocampal microglia-mediated synaptic loss through the gut microbiota and metabolites

Microbiome ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Hongli Shi ◽  
Xing Ge ◽  
Xi Ma ◽  
Mingxuan Zheng ◽  
Xiaoying Cui ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Gut Microbiota ◽  
Neurodegenerative Diseases ◽  
Dietary Fiber ◽  
Brain Aging ◽  
Synaptic Proteins ◽  
Aging Brain ◽  
Normal Brain ◽  
Fiber Intake ◽  
Synaptic Ultrastructure

Abstract Background Cognitive impairment, an increasing mental health issue, is a core feature of the aging brain and neurodegenerative diseases. Industrialized nations especially, have experienced a marked decrease in dietary fiber intake, but the potential mechanism linking low fiber intake and cognitive impairment is poorly understood. Emerging research reported that the diversity of gut microbiota in Western populations is significantly reduced. However, it is unknown whether a fiber-deficient diet (which alters gut microbiota) could impair cognition and brain functional elements through the gut-brain axis. Results In this study, a mouse model of long-term (15 weeks) dietary fiber deficiency (FD) was used to mimic a sustained low fiber intake in humans. We found that FD mice showed impaired cognition, including deficits in object location memory, temporal order memory, and the ability to perform daily living activities. The hippocampal synaptic ultrastructure was damaged in FD mice, characterized by widened synaptic clefts and thinned postsynaptic densities. A hippocampal proteomic analysis further identified a deficit of CaMKIId and its associated synaptic proteins (including GAP43 and SV2C) in the FD mice, along with neuroinflammation and microglial engulfment of synapses. The FD mice also exhibited gut microbiota dysbiosis (decreased Bacteroidetes and increased Proteobacteria), which was significantly associated with the cognitive deficits. Of note, a rapid differentiating microbiota change was observed in the mice with a short-term FD diet (7 days) before cognitive impairment, highlighting a possible causal impact of the gut microbiota profile on cognitive outcomes. Moreover, the FD diet compromised the intestinal barrier and reduced short-chain fatty acid (SCFA) production. We exploit these findings for SCFA receptor knockout mice and oral SCFA supplementation that verified SCFA playing a critical role linking the altered gut microbiota and cognitive impairment. Conclusions This study, for the first time, reports that a fiber-deprived diet leads to cognitive impairment through altering the gut microbiota-hippocampal axis, which is pathologically distinct from normal brain aging. These findings alert the adverse impact of dietary fiber deficiency on brain function, and highlight an increase in fiber intake as a nutritional strategy to reduce the risk of developing diet-associated cognitive decline and neurodegenerative diseases.

Aging

2019 ◽  
pp. 105-112
Author(s):  
Risto Näätänen ◽  
Teija Kujala ◽  
Gregory Light
Keyword(s):  
Hearing Loss ◽  
Speech Perception ◽  
Cognitive Decline ◽  
Temporal Processing ◽  
Brain Aging ◽  
Brain Plasticity ◽  
Part Of Speech ◽  
Memory Traces ◽  
Age Related ◽  
The Brain

This chapter shows that MMN and its magnetoencephalographic (MEG) equivalent MMNm are sensitive indices of aging-related perceptual and cognitive decline. Importantly, the age-related neural changes are associated with a decrease of general brain plasticity, i.e. that of the ability of the brain to form and maintain sensory-memory traces, a necessary basis for veridical perception and appropriate cognitive brain function. MMN/MMNm to change in stimulus duration is particularly affected by aging, suggesting the increased vulnerability of temporal processing to brain aging and accounting, for instance, for a large part of speech-perception difficulties of the aged beyond the age-related peripheral hearing loss.

scholarly journals The Gut Microbiome, Aging, and Longevity: A Systematic Review

Nutrients ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3759
Author(s):  
Varsha D. Badal ◽  
Eleonora D. Vaccariello ◽  
Emily R. Murray ◽  
Kasey E. Yu ◽  
Rob Knight ◽  
...  
Keyword(s):  
Systematic Review ◽  
Older Adults ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Oldest Old ◽  
Amino Acid Synthesis ◽  
Old Adults ◽  
Age Related ◽  
Functional Features ◽  
Functional Pathways

Aging is determined by complex interactions among genetic and environmental factors. Increasing evidence suggests that the gut microbiome lies at the core of many age-associated changes, including immune system dysregulation and susceptibility to diseases. The gut microbiota undergoes extensive changes across the lifespan, and age-related processes may influence the gut microbiota and its related metabolic alterations. The aim of this systematic review was to summarize the current literature on aging-associated alterations in diversity, composition, and functional features of the gut microbiota. We identified 27 empirical human studies of normal and successful aging suitable for inclusion. Alpha diversity of microbial taxa, functional pathways, and metabolites was higher in older adults, particularly among the oldest-old adults, compared to younger individuals. Beta diversity distances significantly differed across various developmental stages and were different even between oldest-old and younger-old adults. Differences in taxonomic composition and functional potential varied across studies, but Akkermansia was most consistently reported to be relatively more abundant with aging, whereas Faecalibacterium, Bacteroidaceae, and Lachnospiraceae were relatively reduced. Older adults have reduced pathways related to carbohydrate metabolism and amino acid synthesis; however, oldest-old adults exhibited functional differences that distinguished their microbiota from that of young-old adults, such as greater potential for short-chain fatty acid production and increased butyrate derivatives. Although a definitive interpretation is limited by the cross-sectional design of published reports, we integrated findings of microbial composition and downstream functional pathways and metabolites, offering possible explanations regarding age-related processes.

scholarly journals A Cross-Sectional Study of Compositional and Functional Profiles of Gut Microbiota in Sardinian Centenarians

mSystems ◽  
2019 ◽  
Vol 4 (4) ◽  
Author(s):  
Lu Wu ◽  
Tiansheng Zeng ◽  
Angelo Zinellu ◽  
Salvatore Rubino ◽  
David J. Kelvin ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Healthy Aging ◽  
High Capacity ◽  
Functional Independence ◽  
Metagenomic Sequencing ◽  
Bifidobacterium Adolescentis ◽  
Content Type ◽  
Age Related ◽  
Genes Encoding ◽  
Functional Profiles

ABSTRACT Sardinia, Italy, has a high prevalence of residents who live more than 100 years. The reasons for longevity in this isolated region are currently unknown. Gut microbiota may hold a clue. To explore the role gut microbiota may play in healthy aging and longevity, we used metagenomic sequencing to determine the compositional and functional differences in gut microbiota associated with populations of different ages in Sardinia. Our data revealed that the gut microbiota of both young and elderly Sardinians shared similar taxonomic and functional profiles. A different pattern was found in centenarians. Within the centenarian group, the gut microbiota was correlated with the functional independence measurement of the host. Centenarians had a higher diversity of core microbiota species and microbial genes than those in the young and elderly. We found that the gut microbiota in Sardinian centenarians displayed a rearranged taxonomic pattern compared with those of the young and elderly, featured by depletion of Faecalibacterium prausnitzii and Eubacterium rectale and enriched for Methanobrevibacter smithii and Bifidobacterium adolescentis. Moreover, functional analysis revealed that the microbiota in centenarians had high capacity for central metabolism, especially glycolysis and fermentation to short-chain fatty acids (SCFAs), although the gut microbiota in centenarians was low in genes encoding enzymes involved in degradation of carbohydrates, including fibers and galactose. IMPORTANCE The gut microbiota has been proposed as a promising determinant for human health. Centenarians as a model for extreme aging may help us understand the correlation of gut microbiota with healthy aging and longevity. Here we confirmed that centenarians had microbiota elements usually associated with benefits to health. Our finding of a high capacity of glycolysis and related SCFA production represented a healthy microbiome and environment that is regarded as beneficial for host gut epithelium. The low abundance of genes encoding components of pathways involved in carbohydrate degradation was also found in the gut microbiota of Sardinian centenarians and is often associated with poor gut health. Overall, our study here represents an expansion of previous research investigating the age-related changes in gut microbiota. Furthermore, our study provides a new prospective for potential targets for gut microbiota intervention directed at limiting gut inflammation and pathology and enhancing a healthy gut barrier.

scholarly journals Ophthalmology: ozone therapy applied to dystrophic maculopathy

Ozone Therapy ◽  
2017 ◽  
Vol 2 (1) ◽  
Author(s):  
Giorgio Grechi
Keyword(s):  
The Body ◽  
Age Related Macular Degeneration ◽  
Antioxidant Systems ◽  
Macular Area ◽  
Ozone Therapy ◽  
Rods And Cones ◽  
Age Related ◽  
Small Structure ◽  
Colloid Cysts ◽  
The Brain

The macula, which is the noblest part of the retina, is a very small structure, containing the photoreceptors (rods and cones) responsible for visual acuity. Over the years, observations have confirmed that alterations that modify the optimal state of the eye also give rise to similar diseases in the brain: ischemias, structural circulatory alterations and neurodegeneration. As the body ages, oxidative alterations take place and they change the antioxidant systems that serves as a neurological and ocular defence. In industrialised nations, age-related macular degeneration is the leading cause of blindness in patients over 55 years of age. Initially, this creates drusen (or colloid cysts) in the macular area.

scholarly journals Mild cognitive impairment (MCI) twenty years on

2011 ◽  
Vol 24 (1) ◽  
pp. 1-5 ◽  
Author(s):  
Karen Ritchie ◽  
Craig W Ritchie
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cognitive Decline ◽  
Brain Aging ◽  
Cognitive Change ◽  
Cognitive Disorder ◽  
Everyday Functioning ◽  
Normal Limits ◽  
Age Related ◽  
The Usa

Cognitive decline has commonly been considered an inevitable result of brain aging and has been of clinical interest principally because of related difficulties with everyday functioning. Since the 1990s the “normality” of age-related cognitive decline has been called into question, being commonly attributed to a number of underlying disorders. Numerous concepts have been proposed which link subclinical cognitive change to pathological states (mild cognitive disorder, mild neurocognitive disorder, mild cognitive impairment). Of these, mild cognitive impairment (MCI) has become the most popular, driven on the one hand by industrial interests seeking to extend new dementia treatments for a more prevalent subclinical syndrome, and on the other by researchers attempting to identify at-risk populations. MCI has been both criticized for “medicalizing” behavior still within normal limits (Stephan et al., 2008; Moreira et al., 2008) and welcomed in that it suggests cognitive decline with aging may not be inevitable, but rather due to abnormalities which could ultimately be treated. Recently, in both Europe (DuBois et al., 2007) and the USA (Albert et al., 2011), panels of experts have scrutinized the concept of MCI and more broadly the pre-dementia stages of neurodegenerative diseases and offered new research diagnostic criteria. These proposed criteria have highlighted the (potential) value of biomarkers in assisting diagnosis, although some have considered the elevation of biomarkers to this level of importance in diagnosing disease before dementia develops to be premature given both the extent and quality of diagnostic biomarker data currently available (McShane et al., 2011a; 2011b).

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