Research perspectives of Biomedical Gerontology and brain aging research: Longevity genes in the brain

Abstract Our aging global population presents a new set of challenges for public health. Individual-disease focused models are becoming outmoded as geriatricians recognize multimorbidity and frailty as the central challenges in preserving health for older adults. Evidence from research into the biology of aging suggests that a set of common cellular-level processes underpin decline in system integrity that induces vulnerability to disease across multiple organ systems, including the brain. In parallel, research in life-course gerontology indicates that the roots of aging-related decline in system integrity extend from early life and encompass histories of social, psychological, and biochemical exposures. The research presented in this symposium aims to integrate these emerging paradigms in aging research by mapping connections among measures of aging in the brain and body and social, psychological, and nutrition exposures. Our symposium focuses on (1) links between social-psychological determinants of health and biological aging in the brain and body; and (2) social and behavioral protective factors that may buffer emerging biological risk in aging. The overarching goal of this symposium is to introduce an approach to gerontology that integrates geroscience with life-course social and psychiatric epidemiology to advance understanding of cognitive aging and functional decline, and ultimately identify novel interventions to extend healthy lifespan.

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CDKN2A Gene Expression as a Potential Aging Biomarker in Dogs

Frontiers in Veterinary Science ◽

10.3389/fvets.2021.660435 ◽

2021 ◽

Vol 8 ◽

Author(s):

Sára Sándor ◽

Kitti Tátrai ◽

Kálmán Czeibert ◽

Balázs Egyed ◽

Enikő Kubinyi

Keyword(s):

Gene Expression ◽

Kinase Inhibitor ◽

Brain Aging ◽

Model Organisms ◽

Aging Research ◽

Temporal Muscle ◽

Cyclin Dependent Kinase Inhibitor ◽

Age Related ◽

The Brain

Describing evolutionary conserved physiological or molecular patterns, which can reliably mark the age of both model organisms and humans or predict the onset of age-related pathologies has become a priority in aging research. The age-related gene-expression changes of the Cyclin Dependent Kinase Inhibitor 2A (CDKN2A) gene have been well-documented in humans and rodents. However, data is lacking from other relevant species, including dogs. Therefore, we quantified the CDKN2A mRNA abundance in dogs of different ages, in four tissue types: the frontal cortex of the brain, temporal muscle, skin, and blood. We found a significant, positive correlation between CDKN2A relative expression values and age in the brain, muscle, and blood; however, no correlation was detected in the skin. The strongest correlation was detected in the brain tissue (CDKN2A/GAPDH: r = 0.757, p < 0.001), similarly to human findings, while the muscle and blood showed weaker, but significant correlation. Our results suggest that CDKN2A might be a potential blood-borne biomarker of aging in dogs, although the validation and optimization will require further, more focused research. Our current results also clearly demonstrate that the role of CDKN2A in aging is conserved in dogs, regarding both tissue specificity and a pivotal role of CDKN2A in brain aging.

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Multiscale Brain Aging in the Context of Neurodegeneration and Alzheimer's Disease

Innovation in Aging ◽

10.1093/geroni/igab046.1435 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. 372-372

Author(s):

Kyra Thrush ◽

Yaroslav Markov

Keyword(s):

Brain Aging ◽

Functional Decline ◽

Organ System ◽

Normal Brain ◽

Molecular Processes ◽

Aging Research ◽

Physical Trauma ◽

New Approaches ◽

Approaches To Study ◽

The Brain

Abstract The brain, with a diverse array of specialized cells, regional substructures, and a relatively isolated microenvironment, represents a uniquely challenging organ system for aging research. The brain can experience physical trauma, interact with the periphery, and is responsible for cognitive and behavioral modifications that can feed back into the molecular processes of aging both within and external to the brain. Advances to our understanding and ability to intervene in the complexity that personifies brain aging and associated neurodegeneration will require integrated, multiscale approaches operating in tandem. Therefore, we have organized this symposium to highlight promising new approaches to study brain aging through the lens of multiple biological levels of organization. We will provide insight not only into normal brain aging, but will also suggest key spurious processes that may drive neurodegeneration and functional decline.

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

GeroPsych ◽

10.1024/1662-9647/a000074 ◽

2012 ◽

Vol 25 (4) ◽

pp. 235-245 ◽

Cited By ~ 64

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.

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Dendrobium officinalis Flower Improves Learning and Reduces Memory Impairment by Mediating Antioxidant Effect and Balancing the Release of Neurotransmitters in Senescent Rats

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207323666200407080352 ◽

2020 ◽

Vol 23 (5) ◽

pp. 402-410 ◽

Cited By ~ 1

Author(s):

Lin-Zi Li ◽

Shan-Shan Lei ◽

Bo Li ◽

Fu-Chen Zhou ◽

Ye-Hui Chen ◽

...

Keyword(s):

Learning And Memory ◽

Brain Aging ◽

Morris Water Maze Test ◽

Control Group ◽

Histopathological Analysis ◽

Hippocampal Damage ◽

Common Belief ◽

Mao B ◽

Positive Effects ◽

The Brain

Aim and Objective: The Dendrobium officinalis flower (DOF) is popular in China due to common belief in its anti-aging properties and positive effects on “nourish yin”. However, there have been relatively few confirmatory pharmacological experiments conducted to date. The aim of this work was to evaluate whether DOF has beneficial effects on learning and memory in senescent rats, and, if so, to determine its potential mechanism of effect. Materials and Methods: SD rats were administrated orally DOF at a dose of 1.38, or 0.46 g/kg once a day for 8 weeks. Two other groups included a healthy untreated control group and a senescent control group. During the 7th week, a Morris water maze test was performed to assess learning and memory. At the end of the experiment, serum and brain samples were collected to measure concentrations of antioxidant enzymes, including malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione reductase (GSH-Px) in serum, and the neurotransmitters, including γ-aminobutyric acid (γ-GABA), Glutamic (Glu), and monoamine oxidase B (MAO-B) in the brain. Histopathology of the hippocampus was assessed using hematoxylin-eosin (H&E) staining. Results: The results suggested that treatment with DOF improved learning as measured by escape latency, total distance, and target quadrant time, and also increased levels of γ-GABA in the brain. In addition, DOF decreased the levels of MDA, Glu, and MAO-B, and improved SOD and GSHPx. Histopathological analysis showed that DOF also significantly reduced structural lesions and neurodegeneration in the hippocampus relative to untreated senescent rats. Conclusion: DOF alleviated brain aging and improved the spatial learning abilities in senescent rats, potentially by attenuating oxidative stress and thus reducing hippocampal damage and balancing the release of neurotransmitters.

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Robert D. Gerry (ed.), Aging and the Brain, (Aging, Vol. 32). New York: Raven Press (1988) 314 pages. ($64.00 U.S.)

Canadian Journal on Aging / La Revue canadienne du vieillissement ◽

10.1017/s0714980800010928 ◽

1989 ◽

Vol 8 (2) ◽

pp. 197-198

Author(s):

M.J. Ball

Keyword(s):

New York ◽

Brain Aging ◽

The Brain

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Effects of Long-Term Treatment with a Blend of Highly Purified Olive Secoiridoids on Cognition and Brain ATP Levels in Aged NMRI Mice

Oxidative Medicine and Cellular Longevity ◽

10.1155/2018/4070935 ◽

2018 ◽

Vol 2018 ◽

pp. 1-10 ◽

Cited By ~ 9

Author(s):

Martina Reutzel ◽

Rekha Grewal ◽

Carmina Silaidos ◽

Jens Zotzel ◽

Stefan Marx ◽

...

Keyword(s):

Mitochondrial Dysfunction ◽

Citrate Synthase ◽

Brain Aging ◽

Mrna Levels ◽

Nmri Mice ◽

Aged Mice ◽

Atp Levels ◽

Long Term Treatment ◽

The Brain

Aging represents a major risk factor for developing neurodegenerative diseases such as Alzheimer’s disease (AD). As components of the Mediterranean diet, olive polyphenols may play a crucial role in the prevention of AD. Since mitochondrial dysfunction acts as a final pathway in both brain aging and AD, respectively, the effects of a mixture of highly purified olive secoiridoids were tested on cognition and ATP levels in a commonly used mouse model for brain aging. Over 6 months, female NMRI mice (12 months of age) were fed with a blend containing highly purified olive secoiridoids (POS) including oleuropein, hydroxytyrosol and oleurosid standardized for 50 mg oleuropein/kg diet (equivalent to 13.75 mg POS/kg b.w.) or the study diet without POS as control. Mice aged 3 months served as young controls. Behavioral tests showed deficits in cognition in aged mice. Levels of ATP and mRNA levels of NADH-reductase, cytochrome-c-oxidase, and citrate synthase were significantly reduced in the brains of aged mice indicating mitochondrial dysfunction. Moreover, gene expression of Sirt1, CREB, Gap43, and GPx-1 was significantly reduced in the brain tissue of aged mice. POS-fed mice showed improved spatial working memory. Furthermore, POS restored brain ATP levels in aged mice which were significantly increased. Our results show that a diet rich in purified olive polyphenols has positive long-term effects on cognition and energy metabolism in the brain of aged mice.

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Design-Based Stereology in Brain Aging Research

Brain Aging ◽

10.1201/9781420005523-4 ◽

2007 ◽

pp. 63-96

Author(s):

Christoph Schmitz ◽

Patrick R. Hof

Keyword(s):

Brain Aging ◽

Aging Research

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

Cells ◽

10.3390/cells10102531 ◽

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.

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Aging

The Mismatch Negativity ◽

10.1093/oso/9780198705079.003.0005 ◽

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.

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