The Impact of Bone on the Biology of Aging

Abstract We hypothesized that bone may secrete hormones that regulate energy metabolism and reproduction. Testing this hypothesis revealed that the osteoblast-specific secreted protein osteocalcin is a hormone regulating glucose homeostasis and male fertility by signaling through a GPCR, Gprc6a, expressed in pancreatic β bells and Leydig cells of the testes. The systematic exploration of osteocalcin biology, revealed that it regulates an unexpectedly large spectrum of physiological functions in the brain and peripheral organs and that it has most features of an antigeromic molecule. As will be presented at the meeting, this body of work suggests that harnessing osteocalcin for therapeutic purposes may be beneficial in the treatment of age-related diseases such as depression, age-related memory loss and the decline in muscle function seen in sarcopenia.

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Age-related differences in the impact of cannabis use on the brain and cognition: a systematic review

European Archives of Psychiatry and Clinical Neuroscience ◽

10.1007/s00406-019-00981-7 ◽

2019 ◽

Vol 269 (1) ◽

pp. 37-58 ◽

Cited By ~ 20

Author(s):

Claire Gorey ◽

Lauren Kuhns ◽

Eleni Smaragdi ◽

Emese Kroon ◽

Janna Cousijn

Keyword(s):

Systematic Review ◽

Cannabis Use ◽

Age Related ◽

The Impact ◽

The Brain

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Neuroscience Research on Human Visual Path Integration: Empirical Overview and Strategic Considerations

10.31234/osf.io/h6u3b ◽

2021 ◽

Author(s):

Jimmy Y. Zhong

Keyword(s):

Path Integration ◽

Hippocampal Formation ◽

Brain Activity ◽

Brain Regions ◽

Neural Basis ◽

Age Related ◽

Neuroscience Research ◽

Integration Strategies ◽

The Impact ◽

The Brain

Over the past two decades, many neuroimaging studies have attempted uncover the brain regions and networks involved in path integration and identify the underlying neurocognitive mechanisms. Although these studies made inroads into the neural basis of path integration, they have yet to offer a full disclosure of the functional specialization of the brain regions supporting path integration. In this paper, I reviewed notable neuroscientific studies on visual path integration in humans, identified the commonalities and discrepancies in their findings, and incorporated fresh insights from recent path integration studies. Specifically, this paper presented neuroscientific studies performed with virtual renditions of the triangle/path completion task and addressed whether or not the hippocampus is necessary for human path integration. Based on studies that showed evidence supporting and negating the involvement of the hippocampal formation in path integration, this paper introduces the proposal that the use of different path integration strategies may determine the extent to which the hippocampus and entorhinal cortex are engaged during path integration. To this end, recent studies that investigated the impact of different path integration strategies on behavioral performance and functional brain activity were discussed. Methodological concerns were raised with feasible recommendations for improving the experimental design of future strategy-related path integration studies, which can cover cognitive neuroscience research on age-related differences in the role of the hippocampal formation in path integration and Bayesian modelling of the interaction between landmark and self-motion cues. The practical value of investigating different path integration strategies was also discussed briefly from a biomedical perspective.

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Neurolinguistics Approach : A Plausible Paradigm in SLA

JOURNAL OF ADVANCES IN LINGUISTICS ◽

10.24297/jal.v2i1.2006 ◽

2014 ◽

Vol 2 (1) ◽

pp. 35-40

Author(s):

Nima Shakouri ◽

Parviz Maftoon ◽

Ogholgol Nazari

Keyword(s):

Second Language ◽

Second Language Acquisition ◽

Language Acquisition ◽

Related Factors ◽

Holistic Perspective ◽

Age Related ◽

The Impact ◽

The Brain ◽

Brain Change

Second language acquisition (SLA) can contribute to the changes in the brain. The paper having a holistic perspective towards the relation between brain and language asserts that the impact of SLA on the brain change is poorly studied. Moreover, claiming that the brain change is dynamic implicates the assumption that the plasticity of the brain is not merely determined by age-related factors. In this regard, experience, in general, and SLA, in particular, has a tremendous effect on the brain change. Thus, resting on the claim that SLA is respected as software and contributes to the function of brain, the paper directs the attention towards agrammatism which attracts much attention from the researchers in neurolinguists. The article also tends to cast lights upon our perceptions towards the notion of change in the brain from the neurolinguistic perspective.

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Multiple Causes of Dementia as Engineered Senescence

European Journal of Medical and Health Sciences ◽

10.24018/ejmed.2020.2.2.227 ◽

2020 ◽

Vol 2 (2) ◽

Author(s):

Mario Dominic Garrett

Keyword(s):

Antagonistic Pleiotropy ◽

Misfolded Protein ◽

Optimal Conditions ◽

Short Term ◽

Trade Off ◽

Age Related ◽

The Many ◽

Biology Of Aging ◽

The Brain

All traumas—cranial, cardiovascular, hormone, viral, bacterial, fungi, parasites, misfolded protein, genetic, behavior, environmental and medication—affect the brain. This paper itemizes studies showing the many different causes of dementia including Alzheimer’s disease. Causes interact with each other, act sequentially by preparing the optimal conditions for its successor, initiate other diseases, allow for other traumas to accumulate and degrade protective features of the brain. Since such age-related cognitive impairment is not exclusively a human attribute there might be support for an evolutionary theory of dementia. Relying on theories of antagonistic pleiotropy and polymorphism, the brain has been designed to sequester trauma. Because of increased longevity, the short-term tactic of sequestering trauma becomes a long-term liability. We are engineered to sequester these insults until a tipping point is reached. Dementia is an evolutionary trade-off for longevity. We cannot cure dementia without understanding the overall biology of aging.

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Age-Related Neurodegeneration and Memory Loss in Down Syndrome

Current Gerontology and Geriatrics Research ◽

10.1155/2012/463909 ◽

2012 ◽

Vol 2012 ◽

pp. 1-13 ◽

Cited By ~ 21

Author(s):

Jason P. Lockrow ◽

Ashley M. Fortress ◽

Ann-Charlotte E. Granholm

Keyword(s):

Down Syndrome ◽

Memory Loss ◽

Memory Deficits ◽

Intervention Strategies ◽

Chromosome 21 ◽

Research Groups ◽

Neuronal Populations ◽

Age Related ◽

The Brain ◽

And Oxidative Stress

Down syndrome (DS) is a condition where a complete or segmental chromosome 21 trisomy causes variable intellectual disability, and progressive memory loss and neurodegeneration with age. Many research groups have examined development of the brain in DS individuals, but studies on age-related changes should also be considered, with the increased lifespan observed in DS. DS leads to pathological hallmarks of Alzheimer's disease (AD) by 40 or 50 years of age. Progressive age-related memory deficits occurring in both AD and in DS have been connected to degeneration of several neuronal populations, but mechanisms are not fully elucidated. Inflammation and oxidative stress are early events in DS pathology, and focusing on these pathways may lead to development of successful intervention strategies for AD associated with DS. Here we discuss recent findings and potential treatment avenues regarding development of AD neuropathology and memory loss in DS.

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THE EFFECTS OF HIGH ADIPOSITY ON CONCENTRIC AND ECCENTRIC MUSCLE PERFORMANCE OF UPPER AND LOWER LIMB MUSCULATURE IN YOUNG AND OLD ADULTS

Applied Physiology Nutrition and Metabolism ◽

10.1139/apnm-2020-0945 ◽

2021 ◽

Author(s):

Sharn Shelley ◽

Rob S James ◽

Steven James Eustace ◽

Emma Eyre ◽

Jason Tallis

Keyword(s):

Older Adults ◽

Body Mass ◽

Muscle Function ◽

Handgrip Strength ◽

Peak Torque ◽

Muscle Performance ◽

Muscle Quality ◽

Upper Body ◽

Age Related ◽

The Impact

The present study uniquely examined the influence of old age and adiposity on maximal concentric and eccentric torque and fatigue of the elbow (EF, EE) and knee (KF, KE) flexors and extensors. 40 males were recruited and categorised into young (n=21, 23.7±3.4) and old (n=19, 68.3±6.1) and then further into normal (young = 16.9±2.5%, old = 20.6±3.1%) and high adiposity (young = 28.9±5.0%, old = 31.3±4.2%) groups. Handgrip strength, sit-to-stand performance, and isokinetic assessments of peak torque at 60°, 120° and 180° s-1 were measured. Older men produced significantly less concentric and eccentric peak torque (P<0.016) but this was not influenced by adiposity (P>0.055). For KE and KF, high adiposity groups demonstrated reduced peak torque normalised to body mass (P<0.021), and muscle and contractile mode specific reduction in torque normalised to segmental lean mass. Eccentric fatigue resistance was unaffected by both age and adiposity (P>0.30) and perceived muscle soreness, measured up to 72 hours post, was only enhanced in the upper body of the young group following eccentric fatigue (P=0.009). Despite the impact of adiposity on skeletal muscle function being comparable between ages, these results suggest high adiposity will have greater impact on functional performance of older adults. Novelty: •Irrespective of age, high adiposity may negatively impact force to body mass ratio and muscle quality in a muscle and contractile mode specific manner. •Whilst the magnitude of adiposity effects is similar across ages, the impact for older adults will be more substantial given the age-related decline in muscle function.

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Effects of Reactive Oxygen and Nitrogen Species on TrkA Expression and Signalling: Implications for proNGF in Aging and Alzheimer’s Disease

Cells ◽

10.3390/cells10081983 ◽

2021 ◽

Vol 10 (8) ◽

pp. 1983

Author(s):

Erika Kropf ◽

Margaret Fahnestock

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Function ◽

Basal Forebrain ◽

Memory Loss ◽

Reactive Oxygen ◽

Neurotrophin Receptor ◽

Nitrogen Species ◽

Age Related ◽

The Brain

Nerve growth factor (NGF) and its precursor form, proNGF, are critical for neuronal survival and cognitive function. In the brain, proNGF is the only detectable form of NGF. Dysregulation of proNGF in the brain is implicated in age-related memory loss and Alzheimer’s disease (AD). AD is characterized by early and progressive degeneration of the basal forebrain, an area critical for learning, memory, and attention. Learning and memory deficits in AD are associated with loss of proNGF survival signalling and impaired retrograde transport of proNGF to the basal forebrain. ProNGF transport and signalling may be impaired by the increased reactive oxygen and nitrogen species (ROS/RNS) observed in the aged and AD brain. The current literature suggests that ROS/RNS nitrate proNGF and reduce the expression of the proNGF receptor tropomyosin-related kinase A (TrkA), disrupting its downstream survival signalling. ROS/RNS-induced reductions in TrkA expression reduce cell viability, as proNGF loses its neurotrophic function in the absence of TrkA and instead generates apoptotic signalling via the pan-neurotrophin receptor p75NTR. ROS/RNS also interfere with kinesin and dynein motor functions, causing transport deficits. ROS/RNS-induced deficits in microtubule motor function and TrkA expression and signalling may contribute to the vulnerability of the basal forebrain in AD. Antioxidant treatments may be beneficial in restoring proNGF signalling and axonal transport and reducing basal forebrain neurodegeneration and related deficits in cognitive function.

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Fiber Tracts Anomalies in APPxPS1 Transgenic Mice Modeling Alzheimer's Disease

Journal of Aging Research ◽

10.4061/2011/281274 ◽

2011 ◽

Vol 2011 ◽

pp. 1-12 ◽

Cited By ~ 6

Author(s):

H. Chen ◽

S. Epelbaum ◽

B. Delatour

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Transgenic Mice ◽

Clinical Symptoms ◽

Anterior Commissure ◽

Fiber Tract ◽

Fiber Tracts ◽

Age Related ◽

The Impact ◽

The Brain

Amyloid beta (A) peptides are known to accumulate in the brain of patients with Alzheimer's disease (AD). However, the link between brain amyloidosis and clinical symptoms has not been elucidated and could be mediated by secondary neuropathological alterations such as fiber tracts anomalies. In the present study, we have investigated the impact of A overproduction in APPxPS1 transgenic mice on the integrity of forebrain axonal bundles (corpus callosum and anterior commissure). We found evidence of fiber tract volume reductions in APPxPS1 mice that were associated with an accelerated age-related loss of axonal neurofilaments and a myelin breakdown. The severity of these defects was neither correlated with the density of amyloid plaques nor associated with cell neurodegeneration. Our data suggest that commissural fiber tract alterations are present in A-overproducing transgenic mice and that intracellular A accumulation preceding extracellular deposits may act as a trigger of such morphological anomalies.

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The Potentials of Methylene Blue as an Anti-Aging Drug

Cells ◽

10.3390/cells10123379 ◽

2021 ◽

Vol 10 (12) ◽

pp. 3379

Author(s):

Huijing Xue ◽

Abhirami Thaivalappil ◽

Kan Cao

Keyword(s):

Oxidative Stress ◽

Methylene Blue ◽

Memory Loss ◽

Skin Aging ◽

Clinical Applications ◽

Premature Aging ◽

Age Related ◽

Wide Range ◽

The Brain ◽

Different Tissues

Methylene blue (MB), as the first fully man-made medicine, has a wide range of clinical applications. Apart from its well-known applications in surgical staining, malaria, and methemoglobinemia, the anti-oxidative properties of MB recently brought new attention to this century-old drug. Mitochondrial dysfunction has been observed in systematic aging that affects many different tissues, including the brain and skin. This leads to increaseding oxidative stress and results in downstream phenotypes under age-related conditions. MB can bypass Complex I/III activity in mitochondria and diminish oxidative stress to some degree. This review summarizes the recent studies on the applications of MB in treating age-related conditions, including neurodegeneration, memory loss, skin aging, and a premature aging disease, progeria.

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WWOX and Its Binding Proteins in Neurodegeneration

Cells ◽

10.3390/cells10071781 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1781

Author(s):

Che-Yu Hsu ◽

Kuan-Ting Lee ◽

Tzu-Yu Sun ◽

Chun-I Sze ◽

Shenq-Shyang Huang ◽

...

Keyword(s):

Protein Aggregation ◽

Binding Proteins ◽

Neuronal Degeneration ◽

Memory Loss ◽

Early Death ◽

Age Related ◽

Gradual Loss ◽

Gsk 3Β ◽

The Brain

WW domain-containing oxidoreductase (WWOX) is known as one of the risk factors for Alzheimer’s disease (AD), a neurodegenerative disease. WWOX binds Tau via its C-terminal SDR domain and interacts with Tau phosphorylating enzymes ERK, JNK, and GSK-3β, and thereby limits AD progression. Loss of WWOX in newborns leads to severe neural diseases and early death. Gradual loss of WWOX protein in the hippocampus and cortex starting from middle age may slowly induce aggregation of a protein cascade that ultimately causes accumulation of extracellular amyloid beta plaques and intracellular tau tangles, along with reduction in inhibitory GABAergic interneurons, in AD patients over 70 years old. Age-related increases in pS14-WWOX accumulation in the brain promotes neuronal degeneration. Suppression of Ser14 phosphorylation by a small peptide Zfra leads to enhanced protein degradation, reduction in NF-κB-mediated inflammation, and restoration of memory loss in triple transgenic mice for AD. Intriguingly, tumor suppressors p53 and WWOX may counteract each other in vivo, which leads to upregulation of AD-related protein aggregation in the brain and lung. WWOX has numerous binding proteins. We reported that the stronger the binding between WWOX and its partners, the better the suppression of cancer growth and reduction in inflammation. In this regard, the stronger complex formation between WWOX and partners may provide a better blockade of AD progression. In this review, we describe whether and how WWOX and partner proteins control inflammatory response and protein aggregation and thereby limit AD progression.

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