scholarly journals Cortical pencil lining on SWI MRI in NBIA and healthy aging

BMC Neurology ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Marlous C. M. van der Weijden ◽  
Peter Jan van Laar ◽  
Roald A. Lambrechts ◽  
Dineke S. Verbeek ◽  
Marina A. J. Tijssen
Keyword(s):  
Globus Pallidus ◽  
Healthy Subjects ◽  
Healthy Aging ◽  
Red Nucleus ◽  
Iron Accumulation ◽  
Specific Marker ◽  
Age Related ◽  
Potential Marker ◽  
Age Dependent ◽  
Subcortical Nuclei

Abstract Background Neurodegeneration with brain iron accumulation (NBIA) is characterized by pathological iron accumulation in the subcortical nuclei and the cortex. As age-related iron accumulation studies in these structures are lacking in healthy aging, we aimed to characterize the dynamics of age-dependent iron accumulation in subcortical nuclei in healthy aging and selected NBIA cases. This is fundamental to understand the natural age-related iron deposition in the healthy brain prior to using this marker as a potential prognostic or diagnostic tool in neurodegenerative disorders. Methods Susceptibility-weighted imaging (SWI) scans from 81 healthy volunteers (0-79 years) and four genetically confirmed patients suffering from NBIA (2-14 years) were obtained. We scored the presence or absence of pencil lining of the motor cortex and putamen and analyzed the normalized SWI signal intensity ratio (NSIR) in five subcortical nuclei. Results In healthy subjects, an age-dependent increase of pencil lining occurred starting from the second decade of life and was present in all cases at the age of 50. In their first decade, NBIA patients showed no cortical pencil lining, but we did observe putaminal pencil lining at this stage. In healthy subjects, age and NSIR of all nuclei correlated positively and was particularly dynamic in early childhood until young adulthood in the globus pallidus, dentate nucleus and red nucleus, but not in the caudate nucleus and putamen. NBIA patients showed an increased NSIR in the globus pallidus only and not in the other subcortical nuclei compared to age-matched healthy subjects. Conclusions Cortical pencil lining is part of healthy aging. This should be considered when assessing this as a potential marker in NBIA diagnosis and prognosis. Putaminal pencil lining has the potential to become a specific marker for some subtypes of NBIA in the first decade of life, as it was only observed in NBIA and not in age-matched healthy subjects. NSIR in the subcortical nuclei during healthy aging was shown to be dynamic, accentuating the importance of having an age-dependent baseline.

scholarly journals Age-dependent changes in mean and variance of gene expression across tissues in a twin cohort

2016 ◽  
Author(s):  
Ana Viñuela ◽  
Andrew A Brown ◽  
Alfonso Buil ◽  
Pei-Chien Tsai ◽  
Matthew N Davies ◽  
...  
Keyword(s):  
Gene Expression ◽  
Healthy Aging ◽  
Process Analysis ◽  
Strong Relationship ◽  
Methylation Array ◽  
Age Related ◽  
Age Dependent ◽  
Mean And Variance ◽  
The Relationship ◽  
Age Related Changes

AbstractGene expression changes with age have consequences for healthy aging and disease development. Here we investigate age-related changes in gene expression measured by RNA-seq in four tissues and the interplay between genotypes and age-related changes in expression. Using concurrently measured methylation array data from fat we also investigate the relationship between methylation, gene expression and age. We identified age-dependent changes in mean levels of gene expression in 5,631 genes and in splicing of 904 genes. Age related changes were widely shared across tissues, with up to 60% of age-related changes in expression and 47% on splicing in multi-exonic genes shared; amongst these we highlight effects on genes involved in diseases such as Alzheimer and cancer. We identified 137 genes with age-related changes in variance and 42 genes with age-dependent discordance between genetically identical individuals; implying the latter are driven by environmental effects. We also give four examples where genetic control of expression is affected by the aging process. Analysis of methylation observed a widespread and stronger effect of age on methylation than expression; however we did not find a strong relationship between age-related changes in both expression and methylation. In summary, we quantified aging affects in splicing, level and variance of gene expression, and show that these processes can be both environmentally and genetically influenced.

scholarly journals Regular and Moderate Exercise Counteracts the Decline of Antioxidant Protection but Not Methylglyoxal-Dependent Glycative Burden in the Ovary of Reproductively Aging Mice

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
S. Falone ◽  
S. Jr Santini ◽  
V. Cordone ◽  
M. Grannonico ◽  
M. Cacchio ◽  
...  
Keyword(s):  
Healthy Aging ◽  
Molecular Mechanisms ◽  
Population Aging ◽  
Oxygen Species ◽  
Moderate Exercise ◽  
Mouse Ovary ◽  
Age Related ◽  
Age Dependent ◽  
Molecular Damage

Population aging results in urgent needs of interventions aimed at ensuring healthy senescence. Exercise often results in healthy aging, yet many molecular mechanisms underlying such effects still need to be identified. We here investigated whether the age-dependent accumulation of oxidative and methylglyoxal- (MG-) related molecular damage could be delayed by moderate exercise in the mouse ovary, an organ that first exhibits impaired function with advancing age in mammals. CD1 female mice underwent two- or four-month treadmill-based running through the transition from adult to middle age, when ovaries show signs of senescence, and markers of protection against reactive oxygen species (ROS) and MG were measured. The long-term exercise reduced the protein oxidative damage in the ovaries (P<0.01), and this was linked to the preservation of the glutathione peroxidase protection against ROS (P<0.001), as well as to the increased glutathione availability (P<0.001). Conversely, even though the age-related deactivation of the MG-targeting systems was partially prevented by the long-term running programme (P<0.001), exercised mice were not protected from the age-dependent glycative burden. In summary, lately initiated regular and moderate exercise limited some changes occurring in the ovaries of middle-aged mice, and this might help to develop nonpharmacological cointerventions to reduce the vulnerability of mammalian ovaries towards redox dysfunctions.

scholarly journals Microenvironment-contextual cell signaling is attenuated with age

2019 ◽  
Author(s):  
Henriette C. Ertsås ◽  
Mark A. LaBarge ◽  
James B Lorens
Keyword(s):  
Breast Cancer ◽  
Epithelial Cells ◽  
Cell Signaling ◽  
Cancer Susceptibility ◽  
Breast Cancer Susceptibility ◽  
Mammary Epithelial ◽  
Specific Marker ◽  
Breast Cancers ◽  
Age Related ◽  
Age Dependent

AbstractPost-menopausal women are more prone to breast cancer than younger women. The increased frequency of age-related breast cancers is likely due to interactions between acquired mutations and age-dependent epigenetic changes that affect mammary epithelial lineage fidelity. We hypothesized that the aging process fundamentally affects how human mammary epithelial cells (HMEC) respond to microenvironmental signals, resulting in increased susceptibility to oncogenic transformation. In order to measure microenvironmental cell signaling in normal finite lifespan HMEC, we applied a novel microsphere-based flow cytometry technology. The microsphere cytometry allows multiparametric single cell quantification of signaling pathway activity and lineage-specific marker expression in cells adhered to surface-functionalized microspheres that mimic specific microenvironments. Using this approach, we analyzed age-dependent changes in human mammary myoepithelial and luminal epithelial cells exposed to different ECM and growth factors. We found that ECM–mediated MAP kinase and PI3 kinase activation levels in HMEC were attenuated with age. Older luminal cells displayed higher surface integrin levels consistent with acquired basal identity, albeit with decreased integrin activation and increased Src-signaling relative to myoepithelial cells. We show that the diminished signaling magnitude in HMEC from older women correlated with reduced probability of activating oncogene-induced senescence. We propose that age-related changes in ECM-mediated epithelial cell regulation may impair protective tumor suppression mechanisms and increase breast cancer susceptibility.

scholarly journals Scotopic thresholds on dark-adapted chromatic perimetry in healthy aging and age-related macular degeneration

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Manjot Kaur Grewal ◽  
Shruti Chandra ◽  
Alan Bird ◽  
Glen Jeffery ◽  
Sobha Sivaprasad
Keyword(s):  
Macular Degeneration ◽  
Healthy Aging ◽  
Intraclass Correlation ◽  
Age Related Macular Degeneration ◽  
Healthy Individuals ◽  
Age Related ◽  
Rod Function ◽  
The Mean ◽  
Highly Correlated ◽  
Effect Of Age

AbstractTo evaluate the effect of aging, intra- and intersession repeatability and regional scotopic sensitivities in healthy and age-related macular degeneration (AMD) eyes. Intra- and intersession agreement and effect of age was measured in healthy individuals. The mean sensitivity (MS) and pointwise retinal sensitivities (PWS) within the central 24° with 505 nm (cyan) and 625 nm (red) stimuli were evaluated in 50 individuals (11 healthy and 39 AMD eyes). The overall intra- and intersession had excellent reliability (intraclass correlation coefficient, ICC > 0.90) and tests were highly correlated (Spearman rs = 0.75–0.86). Eyes with subretinal drusenoid deposit (SDD) had reduced PWS centrally, particularly at inferior and nasal retinal locations compared with controls and intermediate AMD (iAMD) without SDD. There was no difference in MS or PWS at any retinal location between iAMD without SDD and healthy individuals nor between iAMD with SDD and non-foveal atrophic AMD groups. Eyes with SDD have reduced rod function compared to iAMD without SDD and healthy eyes, but similar to eyes with non-foveal atrophy. Our results highlight rod dysfunction is not directly correlated with drusen load and SDD location.

scholarly journals The serotonin transporter gene and female personality variation in a free-living passerine

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Bert Thys ◽  
Andrea S. Grunst ◽  
Nicky Staes ◽  
Rianne Pinxten ◽  
Marcel Eens ◽  
...  
Keyword(s):  
Serotonin Transporter ◽  
Strong Support ◽  
Serotonin Transporter Gene ◽  
Female Aggression ◽  
Nucleotide Polymorphisms ◽  
Transporter Gene ◽  
Evolutionary Potential ◽  
Free Living ◽  
Age Related ◽  
Age Dependent

AbstractQuantifying variation in behaviour-related genes provides insight into the evolutionary potential of repeatable among-individual variation in behaviour (i.e. personality). Yet, individuals typically also plastically adjust their behaviour in response to environmental conditions and/or age, thereby complicating the detection of genotype–phenotype associations. Here, using a population of free-living great tits (Parus major), we assessed the association between single nucleotide polymorphisms (SNPs) in the serotonin transporter gene (SERT) and two repeatable behavioural traits, i.e. female-female aggression and female hissing behaviour. For female-female aggression, a trait showing age-related plasticity, we found no evidence for associations with SERT SNPs, even when assessing potential age-dependent effects of SERT genotype on aggression. We also found no strong support for associations between SERT SNPs and hissing behaviour, yet we identified two synonymous polymorphisms (exon 13 SNP66 and exon 12 SNP144) of particular interest, each explaining about 1.3% of the total variation in hissing behaviour. Overall, our results contribute to the general understanding of the biological underpinning of complex behavioural traits and will facilitate further (meta-analytic) research on behaviour-related genes. Moreover, we emphasize that future molecular genetic studies should consider age-dependent genotype–phenotype associations for behavioural trait (co)variation, as this will vastly improve our understanding of the proximate causes and ultimate consequences of personality variation in natural populations.

scholarly journals MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Joseph C. Reynolds ◽  
Rochelle W. Lai ◽  
Jonathan S. T. Woodhead ◽  
James H. Joly ◽  
Cameron J. Mitchell ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Healthy Aging ◽  
Metabolic Stress ◽  
Muscle Metabolism ◽  
Physical Capacity ◽  
Physical Decline ◽  
Age Dependent ◽  
Exercise Induced ◽  
Muscle Homeostasis ◽  
Metabolic Fitness

AbstractHealthy aging can be promoted by enhanced metabolic fitness and physical capacity. Mitochondria are chief metabolic organelles with strong implications in aging that also coordinate broad physiological functions, in part, using peptides that are encoded within their independent genome. However, mitochondrial-encoded factors that actively regulate aging are unknown. Here, we report that mitochondrial-encoded MOTS-c can significantly enhance physical performance in young (2 mo.), middle-age (12 mo.), and old (22 mo.) mice. MOTS-c can regulate (i) nuclear genes, including those related to metabolism and proteostasis, (ii) skeletal muscle metabolism, and (iii) myoblast adaptation to metabolic stress. We provide evidence that late-life (23.5 mo.) initiated intermittent MOTS-c treatment (3x/week) can increase physical capacity and healthspan in mice. In humans, exercise induces endogenous MOTS-c expression in skeletal muscle and in circulation. Our data indicate that aging is regulated by genes encoded in both of our co-evolved mitochondrial and nuclear genomes.

scholarly journals Random errors in protein synthesis activate an age-dependent program of muscle atrophy in mice

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
James Moore ◽  
Rashid Akbergenov ◽  
Martina Nigri ◽  
Patricia Isnard-Petit ◽  
Amandine Grimm ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Muscle Atrophy ◽  
Strength Analysis ◽  
Dependent Manner ◽  
Random Errors ◽  
Age Related ◽  
Related Phenotype ◽  
Age Dependent ◽  
Translation Accuracy ◽  
Transcriptomic Changes

AbstractRandom errors in protein synthesis are prevalent and ubiquitous, yet their effect on organismal health has remained enigmatic for over five decades. Here, we studied whether mice carrying the ribosomal ambiguity (ram) mutation Rps2-A226Y, recently shown to increase the inborn error rate of mammalian translation, if at all viable, present any specific, possibly aging-related, phenotype. We introduced Rps2-A226Y using a Cre/loxP strategy. Resulting transgenic mice were mosaic and showed a muscle-related phenotype with reduced grip strength. Analysis of gene expression in skeletal muscle using RNA-Seq revealed transcriptomic changes occurring in an age-dependent manner, involving an interplay of PGC1α, FOXO3, mTOR, and glucocorticoids as key signaling pathways, and finally resulting in activation of a muscle atrophy program. Our results highlight the relevance of translation accuracy, and show how disturbances thereof may contribute to age-related pathologies.

scholarly journals Nutrition for Older Athletes: Focus on Sex-Differences

Nutrients ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1409
Author(s):  
Barbara Strasser ◽  
Dominik Pesta ◽  
Jörn Rittweger ◽  
Johannes Burtscher ◽  
Martin Burtscher
Keyword(s):  
Sex Differences ◽  
Exercise Training ◽  
Role Model ◽  
Healthy Aging ◽  
Endurance Performance ◽  
Metabolic Efficiency ◽  
Older Athletes ◽  
Age Related ◽  
Masters Athletes ◽  
Physical Capacities

Regular physical exercise and a healthy diet are major determinants of a healthy lifespan. Although aging is associated with declining endurance performance and muscle function, these components can favorably be modified by regular physical activity and especially by exercise training at all ages in both sexes. In addition, age-related changes in body composition and metabolism, which affect even highly trained masters athletes, can in part be compensated for by higher exercise metabolic efficiency in active individuals. Accordingly, masters athletes are often considered as a role model for healthy aging and their physical capacities are an impressive example of what is possible in aging individuals. In the present review, we first discuss physiological changes, performance and trainability of older athletes with a focus on sex differences. Second, we describe the most important hormonal alterations occurring during aging pertaining regulation of appetite, glucose homeostasis and energy expenditure and the modulatory role of exercise training. The third part highlights nutritional aspects that may support health and physical performance for older athletes. Key nutrition-related concerns include the need for adequate energy and protein intake for preventing low bone and muscle mass and a higher demand for specific nutrients (e.g., vitamin D and probiotics) that may reduce the infection burden in masters athletes. Fourth, we present important research findings on the association between exercise, nutrition and the microbiota, which represents a rapidly developing field in sports nutrition.

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