scholarly journals Adropin expression correlates with aging-related neuropathology in the human brain and improves neuroinflammation and cognitive function in aging mice

2021 ◽  
Author(s):  
Subhashis Banerjee ◽  
Sarbani Ghoshal ◽  
Clemence Girardet ◽  
Kelly M. DeMars ◽  
Changjun Yang ◽  
...  
Keyword(s):  
Cellular Metabolism ◽  
Enrichment Analysis ◽  
Spatial Learning And Memory ◽  
Oligodendrocyte Progenitor Cells ◽  
Protein Markers ◽  
Novel Therapy ◽  
Markers Of Inflammation ◽  
Expression Of Genes ◽  
Age Related ◽  
And Function

Abstract The neural functions of adropin, a secreted peptide highly expressed in the brain, have not been investigated. In humans, adropin is highly expressed in astrocytes and peaks during critical postnatal periods of brain development. Gene enrichment analysis of transcripts correlating with adropin expression suggests processes relevance to aging-related neurodegenerative diseases that vary with age and dementia state, possibly indicating survivor bias. In people aged <40y and ‘oldold’ (>75y) diagnosed with dementia, adropin correlates positively with genes involved in mitochondrial processes. In the ‘old-old’ without dementia adropin expression correlates positively with morphogenesis and synapse function. Potent neurotrophic responses in primary cultured neurons are consistent with adropin supporting the development and function of neural networks. Adropin expression in the ‘old-old’ also correlates positively with protein markers of tau-related neuropathologies and inflammation, particularly in those without dementia. How variation in brain adropin expression affects neurological aging was investigated using old (18- month) C57BL/6J mice. In mice adropin is expressed in neurons, oligodendrocyte progenitor cells, oligodendrocytes, and microglia and shows correlative relationships with groups of genes involved in neurodegeneration and cellular metabolism. Increasing adropin expression using transgenesis improved spatial learning and memory, novel object recognition, resilience to exposure to new environments, and reduced mRNA markers of inflammation in old mice. Treatment with synthetic adropin peptide also reversed age-related declines of cognitive functions and affected expression of genes involved in morphogenesis and cellular metabolism. Collectively, these results establish a link between adropin expression and neural energy metabolism and indicate a potential novel therapy against neurological aging.

scholarly journals Adropin correlates with aging-related neuropathology in humans and improves cognitive function in aging mice

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Subhashis Banerjee ◽  
Sarbani Ghoshal ◽  
Clemence Girardet ◽  
Kelly M. DeMars ◽  
Changjun Yang ◽  
...  
Keyword(s):  
Cellular Metabolism ◽  
Enrichment Analysis ◽  
Spatial Learning And Memory ◽  
Oligodendrocyte Progenitor Cells ◽  
Protein Markers ◽  
Markers Of Inflammation ◽  
Expression Of Genes ◽  
Age Related ◽  
And Function ◽  
Mrna Markers

AbstractThe neural functions of adropin, a secreted peptide highly expressed in the brain, have not been investigated. In humans, adropin is highly expressed in astrocytes and peaks during critical postnatal periods of brain development. Gene enrichment analysis of transcripts correlating with adropin expression suggests processes relevant to aging-related neurodegenerative diseases that vary with age and dementia state, possibly indicating survivor bias. In people aged <40 y and ‘old-old’ (>75 y) diagnosed with dementia, adropin correlates positively with genes involved in mitochondrial processes. In the ‘old-old’ without dementia adropin expression correlates positively with morphogenesis and synapse function. Potent neurotrophic responses in primary cultured neurons are consistent with adropin supporting the development and function of neural networks. Adropin expression in the ‘old-old’ also correlates positively with protein markers of tau-related neuropathologies and inflammation, particularly in those without dementia. How variation in brain adropin expression affects neurological aging was investigated using old (18-month) C57BL/6J mice. In mice adropin is expressed in neurons, oligodendrocyte progenitor cells, oligodendrocytes, and microglia and shows correlative relationships with groups of genes involved in neurodegeneration and cellular metabolism. Increasing adropin expression using transgenesis improved spatial learning and memory, novel object recognition, resilience to exposure to new environments, and reduced mRNA markers of inflammation in old mice. Treatment with synthetic adropin peptide also reversed age-related declines in cognitive functions and affected expression of genes involved in morphogenesis and cellular metabolism. Collectively, these results establish a link between adropin expression and neural energy metabolism and indicate a potential therapy against neurological aging.

scholarly journals The Microalgae Aurantiochytrium Sp. Increases Neurogenesis and Improves Spatial Learning and Memory in Senescence-Accelerated Prone 8 Mice

2020 ◽  
Author(s):  
Kazunori Sasaki ◽  
Noelia Geribaldi-Doldan ◽  
Qingqing Wu ◽  
Julie Davies ◽  
Francis G. Szele ◽  
...  
Keyword(s):  
Stem Cells ◽  
Learning And Memory ◽  
Spatial Learning ◽  
Neural Development ◽  
Learning Ability ◽  
Morris Water Maze Test ◽  
Spatial Learning And Memory ◽  
Age Related ◽  
And Function ◽  
Samp8 Mice

Abstract Background Much attention has recently focused on nutraceuticals which are widely used to promote health. In particular, nutraceuticals with minimal side effects have been developed for preventing or treating neurological diseases such as Alzheimer’s disease (AD). The present study was conducted to investigate the potential effect on neural development and function of the microalgae Aurantiochytrium sp. as a nutraceutical. Methods To test the neuroprotection of ethanol extract of Aurantiochytrium (EEA) and n-Hex layer of EEA (HEEA), amyloid-beta (Aβ)-stimulated SH-SY5Y cells was used for in vitro AD model. We then assessed the enhancement of neurogenesis of EEA and HEEA using murine ex vivo neurospheres. We also administered EEA or HEEA to SAMP8 mice, a non-transgenic strain with accelerated aging and Alzheimer’s-like memory loss for evaluation of spatial learning and memory using MWM test. Finally, we performed immunohistochemical analysis using mice brain fed with EEA for assessment of neurogenesis. Results Pre-treatment of SH-SY5Y cells with EEA or the squalene-rich fraction of EEA, n-Hex layer (HEEA), ameliorated Aβ-induced cytotoxicity. Interestingly, only EEA-treated cells showed a significant increase in cell metabolism and intracellular ATP production. Moreover, EEA treatment significantly increased the number of neurospheres, whilst HEEA treatment significantly increased the number of β-III-tubulin + young neurons and GFAP + astrocytes. SAMP8 mice were given 50 mg/kg EEA or HEEA orally for 30 days. Learning ability was assessed in the Morris water maze test. EEA and HEEA decreased escape latency time in SAMP8 mice, indicating improved memory. To detect activated stem cells and newborn neurons, we administered BrdU for 9 days and measured BrdU + cells in the dentate gyrus, a neurogenic stem cell niche of the hippocampus. In SAMP8 mice, EEA rapidly and significantly increased the number of BrdU + GFAP + stem cells as well as their progeny, BrdU + NeuN + mature neurons. Conclusions Our data in aggregate indicate that EEA and its constituents could be developed into a nutraceutical for promoting brain health and function against some age-related diseases including neurodegenerative desease, particularly AD.

scholarly journals Triple nanoemulsion potentiates the effects of topical treatments with microencapsulated retinol and modulates biological processes related to skin aging

2013 ◽  
Vol 88 (6) ◽  
pp. 930-936 ◽  
Author(s):  
Alessandro Afornali ◽  
Rodrigo de Vecchi ◽  
Rodrigo Makowiecky Stuart ◽  
Gustavo Dieamant ◽  
Luciana Lima de Oliveira ◽  
...  
Keyword(s):  
Genetic Factors ◽  
Biological Process ◽  
Ex Vivo ◽  
Skin Aging ◽  
Biological Processes ◽  
Skin Damage ◽  
Expression Of Genes ◽  
Age Related ◽  
Reverse Transcription Quantitative Pcr ◽  
And Function

BACKGROUND: The sum of environmental and genetic factors affects the appearance and function of the skin as it ages. The identification of molecular changes that take place during skin aging provides biomarkers and possible targets for therapeutic intervention. Retinoic acid in different formulations has emerged as an alternative to prevent and repair age-related skin damage. OBJECTIVES: To understand the effects of different retinoid formulations on the expression of genes associated with biological processes that undergo changes during skin aging. METHODS: Ex-vivo skin samples were treated topically with different retinoid formulations. The modulation of biological processes associated with skin aging was measured by Reverse Transcription quantitative PCR (RT-qPCR). RESULTS: A formulation containing microencapsulated retinol and a blend of active ingredients prepared as a triple nanoemulsion provided the best results for the modulation of biological, process-related genes that are usually affected during skin aging. CONCLUSION: This association proved to be therapeutically more effective than tretinoin or microencapsulated retinol used singly.

scholarly journals Increased Endogenous GDNF in Mice Protects Against Age-Related Decline in Neuronal Cholinergic Markers

2021 ◽  
Vol 13 ◽  
Author(s):  
Sumonto Mitra ◽  
Giorgio Turconi ◽  
Taher Darreh-Shori ◽  
Kärt Mätlik ◽  
Matilde Aquilino ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Cholinergic Neurons ◽  
Lewy Body Dementia ◽  
Cholinergic Transmission ◽  
Expression Of Genes ◽  
Age Related ◽  
Y Maze ◽  
In The Wild ◽  
And Function ◽  
Cholinergic Markers

Gradual decline in cholinergic transmission and cognitive function occurs during normal aging, whereas pathological loss of cholinergic function is a hallmark of different types of dementia, including Alzheimer’s disease (AD), Lewy body dementia (LBD), and Parkinson’s disease dementia (PDD). Glial cell line-derived neurotrophic factor (GDNF) is known to modulate and enhance the dopamine system. However, how endogenous GDNF influences brain cholinergic transmission has remained elusive. In this study, we explored the effect of a twofold increase in endogenous GDNF (Gdnf hypermorphic mice, Gdnfwt/hyper) on cholinergic markers and cognitive function upon aging. We found that Gdnfwt/hyper mice resisted an overall age-associated decline in the cholinergic index observed in the brain of Gdnfwt/wt animals. Biochemical analysis revealed that the level of nerve growth factor (NGF), which is important for survival and function of central cholinergic neurons, was significantly increased in several brain areas of old Gdnfwt/hyper mice. Analysis of expression of genes involved in cholinergic transmission in the cortex and striatum confirmed modulation of cholinergic pathways by GDNF upon aging. In line with these findings, Gdnfwt/hyper mice did not undergo an age-related decline in cognitive function in the Y-maze test, as observed in the wild type littermates. Our results identify endogenous GDNF as a potential modulator of cholinergic transmission and call for future studies on endogenous GDNF function in neurodegenerative disorders characterized by cognitive impairments, including AD, LBD, and PDD.

scholarly journals Adropin expression correlates with age-related neuropathologies in the human brain and improves neuroinflammation and cognitive function in aging mice

2021 ◽  
Author(s):  
Subhashis Banerjee ◽  
Sarbani Ghoshal ◽  
Clemence Girardet ◽  
Kelly M. DeMars ◽  
Changjun Yang ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Human Brain ◽  
Stress Responses ◽  
Gene Clusters ◽  
Mitochondrial Metabolism ◽  
Protein Markers ◽  
Human Brain Tissue ◽  
Markers Of Inflammation ◽  
Age Related ◽  
Old Mice

Abstract Adropin is most abundant in neural tissues yet its neurological functions are unclear. Data from post-mortem human brain tissue samples indicates adropin expression occurs predominantly in astrocytes, peaks during critical post-natal periods of brain development, and then declines with aging. Previous experiments indicate adropin regulates mitochondrial metabolism. Gene clusters correlating with adropin are age- and dementia-specific, possibly indicating survivor bias. In people aged <40y adropin correlates positively with genes involved in mitochondrial metabolism, APOE and Clusterin. In the ‘old-old’ (>75y) with dementia, adropin expression correlates with genes linked to mitochondrial metabolism and neurodegenerative conditions. In the ‘old-old’ (>75y) without dementia, adropin correlates with genes involved in morphogenesis, growth of neuronal processes (dendrites, axons) and synapse function. Accordingly, adropin elicits neurotrophic responses in primary cultured neurons. Adropin expression also correlates positively with protein markers of tau-related neuropathologies and inflammation, particularly in people without dementia, indicating a link to cellular stressors. How variation in brain adropin expression affects neurological aging was investigated using C57BL/6J mice. In mice, adropin is more widely expressed in neurons, oligodendrocyte progenitor cells, oligodendrocytes, and microglia. Preventing the decline in expression observed with aging of mice using transgenesis improved cognitive function and resilience, while also reducing mRNA markers of inflammation in 18-month old mice. Treating 18-month old mice with adropin peptide also improved cognitive performance. These results link adropin expression to cellular energy metabolism and stress responses in the brain and indicates a possible relationship with aging-related cognitive decline.

scholarly journals Exosome-Mediated Activation of Neuronal Cells Triggered by γ-Aminobutyric Acid (GABA)

Nutrients ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 2544
Author(s):  
Ryo Inotsuka ◽  
Miyako Udono ◽  
Atsushi Yamatsu ◽  
Mujo Kim ◽  
Yoshinori Katakura
Keyword(s):  
Oral Administration ◽  
Memory Function ◽  
Neuronal Cells ◽  
Neuronal Cell ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Aminobutyric Acid ◽  
Intestinal Cells ◽  
Cell Functions ◽  
Expression Of Genes

γ-Aminobutyric acid (GABA) is a potent bioactive amino acid, and several studies have shown that oral administration of GABA induces relaxation, improves sleep, and reduces psychological stress and fatigue. In a recent study, we reported that exosomes derived from GABA-treated intestinal cells serve as signal transducers that mediate brain–gut interactions. Therefore, the purpose of this study was to verify the functionality of GABA-derived exosomes and to examine the possibility of improving memory function following GABA administration. The results showed that exosomes derived from GABA-treated intestinal cells (Caco-2) activated neuronal cells (SH-SY5Y) by regulating genes related to neuronal cell functions. Furthermore, we found that exosomes derived from the serum of GABA-treated mice also activated SH-SY5Y cells, indicating that exosomes, which are capable of activating neuronal cells, circulate in the blood of mice orally administered GABA. Finally, we performed a microarray analysis of mRNA isolated from the hippocampus of mice that were orally administered GABA. The results revealed changes in the expression of genes related to brain function. Gene Set Enrichment Analysis (GSEA) showed that oral administration of GABA affected the expression of genes related to memory function in the hippocampus.

scholarly journals Molecular and phenotypic analysis of rodent models reveals conserved and species-specific modulators of human sarcopenia

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Anastasiya Börsch ◽  
Daniel J. Ham ◽  
Nitish Mittal ◽  
Lionel A. Tintignac ◽  
Eugenia Migliavacca ◽  
...  
Keyword(s):  
Muscle Mass ◽  
Inflammatory Responses ◽  
Molecular Data ◽  
Model Organisms ◽  
Sequencing Data ◽  
Phenotypic Analysis ◽  
Age Related ◽  
Analogous Data ◽  
Species Specific ◽  
And Function

AbstractSarcopenia, the age-related loss of skeletal muscle mass and function, affects 5–13% of individuals aged over 60 years. While rodents are widely-used model organisms, which aspects of sarcopenia are recapitulated in different animal models is unknown. Here we generated a time series of phenotypic measurements and RNA sequencing data in mouse gastrocnemius muscle and analyzed them alongside analogous data from rats and humans. We found that rodents recapitulate mitochondrial changes observed in human sarcopenia, while inflammatory responses are conserved at pathway but not gene level. Perturbations in the extracellular matrix are shared by rats, while mice recapitulate changes in RNA processing and autophagy. We inferred transcription regulators of early and late transcriptome changes, which could be targeted therapeutically. Our study demonstrates that phenotypic measurements, such as muscle mass, are better indicators of muscle health than chronological age and should be considered when analyzing aging-related molecular data.

The Association Between Sarcopenia and Postoperative Outcomes Among Older Adults With Hip Fracture: A Systematic Review

2021 ◽  
pp. 073346482110065
Author(s):  
Ming-Hsiu Chiang ◽  
Yi-Jie Kuo ◽  
Yu-Pin Chen
Keyword(s):  
Systematic Review ◽  
Older Adults ◽  
Hip Fracture ◽  
Postoperative Mortality ◽  
Clinical Event ◽  
High Morbidity ◽  
Adverse Health Outcomes ◽  
Age Related ◽  
Study Selection ◽  
And Function

Hip fracture is a serious clinical event with high morbidity and mortality. Sarcopenia is characterized by age-related loss of muscle mass and function, leading to several adverse health outcomes. In this systematic review, no limitation criteria were used for study selection and 327 studies were identified in the initial search. Of these, 11 studies comprising a total of 2,314 patients were selected. The overall proportion of older adults with hip fracture having sarcopenia was 44%, with a disparity of approximately 10% between men and women. Most studies have indicated that older adults with sarcopenia had poorer postoperative functional recovery than those without sarcopenia; the association between sarcopenia and high postoperative mortality or long hospital stay was heterogeneous. Well-organized studies with longer follow-up periods are warranted.

scholarly journals Targeting Senescent Cells to Counter Aging and Aging-Related Conditions

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 818-818
Author(s):  
Nathan LeBrasseur
Keyword(s):  
Human Populations ◽  
Geriatric Syndromes ◽  
Preclinical Models ◽  
Pharmacological Agents ◽  
New Class ◽  
Age Related ◽  
Selective Elimination ◽  
Early Phase Clinical Trials ◽  
And Function ◽  
State Of The Science

Abstract In response to various forms of age-associated damage, cells can enter a state of senescence. Senescent cells can compromise the health and function of a tissue, and their accumulation with advancing age is believed to contribute to age-related diseases and geriatric syndromes. In preclinical models (i.e., mice), selective elimination of senescent cells through either genetic approaches or a new class of pharmacological agents, termed “senolytics”, has been show to effectively delay, prevent, or reverse the onset and/or progression of pulmonary disease, osteoporosis, atherosclerosis, diabetes, cognitive decline, and several other conditions. Thus, considerable efforts are underway to optimize pharmacological strategies and test their effectiveness in human populations. This seminar will highlight the state-of-the-science of senolytic drugs, and the opportunities and challenges for early phase clinical trials in humans.

scholarly journals Telomere Length and Oxidative Stress and Its Relation with Metabolic Syndrome Components in the Aging

Biology ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 253
Author(s):  
Graciela Gavia-García ◽  
Juana Rosado-Pérez ◽  
Taide Laurita Arista-Ugalde ◽  
Itzen Aguiñiga-Sánchez ◽  
Edelmiro Santiago-Osorio ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Metabolic Syndrome ◽  
Telomere Length ◽  
Scientific Evidence ◽  
Telomeric Dna ◽  
Biochemical Alterations ◽  
The Metabolic Syndrome ◽  
Age Related ◽  
And Function

A great amount of scientific evidence supports that Oxidative Stress (OxS) can contribute to telomeric attrition and also plays an important role in the development of certain age-related diseases, among them the metabolic syndrome (MetS), which is characterised by clinical and biochemical alterations such as obesity, dyslipidaemia, arterial hypertension, hyperglycaemia, and insulin resistance, all of which are considered as risk factors for type 2 diabetes mellitus (T2DM) and cardiovascular diseases, which are associated in turn with an increase of OxS. In this sense, we review scientific evidence that supports the association between OxS with telomere length (TL) dynamics and the relationship with MetS components in aging. It was analysed whether each MetS component affects the telomere length separately or if they all affect it together. Likewise, this review provides a summary of the structure and function of telomeres and telomerase, the mechanisms of telomeric DNA repair, how telomere length may influence the fate of cells or be linked to inflammation and the development of age-related diseases, and finally, how the lifestyles can affect telomere length.

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