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 Neutrophil response to cyclophosphamide predicts resilience to age-related learning impairment

2020 ◽  
Vol 2 (4) ◽  
pp. 230-231
Author(s):  
Katie Nickel ◽  
◽  
Marianne Bjorner ◽  
Warren Ladiges ◽  
Lida Zhu
Keyword(s):  
Middle Age ◽  
Punch Biopsy ◽  
Dependent Manner ◽  
Cell Counts ◽  
Age Related ◽  
Age Dependent ◽  
White Blood Cell Counts ◽  
Improved Learning ◽  
Learning Impairment ◽  
Neutrophil Response

The ability to respond to stress, defined as resilience, was measured by white blood cell counts in C57BL/6 mice of various ages receiving a nonlethal dose of cyclophosphamide (CYP). Neutrophil counts dipped and then rebounded in a consistent and age-dependent manner. Low neutrophil rebound correlated with improved learning in middle-age mice suggesting CYP-nduced neutrophil response may predict resilience to aging. Keywords: Resilience to aging, wound healing, ear punch biopsy, aging mice

scholarly journals Aging Does Not Exacerbate Muscle Loss During Denervation and Lends Unique Muscle-Specific Atrophy Resistance With Akt Activation

2021 ◽  
Vol 12 ◽  
Author(s):  
Jae-Sung You ◽  
Jie Chen
Keyword(s):  
Muscle Atrophy ◽  
Stress Responses ◽  
Mammalian Target Of Rapamycin ◽  
Akt Signaling ◽  
Skeletal Muscle Atrophy ◽  
Muscle Loss ◽  
Akt Activation ◽  
Age Related ◽  
Age Dependent ◽  
Old Mice

Sarcopenia, or age-related skeletal muscle atrophy and weakness, imposes significant clinical and economic burdens on affected patients and societies. Neurological degeneration, such as motoneuron death, has been recognized as a key contributor to sarcopenia. However, little is known about how aged/sarcopenic muscle adapts to this denervation stress. Here, we show that mice at 27months of age exhibit clear signs of sarcopenia but no accelerated denervation-induced muscle atrophy when compared to 8-month-old mice. Surprisingly, aging lends unique atrophy resistance to tibialis anteria muscle, accompanied by an increase in the cascade of mammalian target of rapamycin complex 1 (mTORC1)-independent anabolic events involving Akt signaling, rRNA biogenesis, and protein synthesis during denervation. These results expand our understanding of age-dependent stress responses and may help develop better countermeasures to sarcopenia.

scholarly journals Age-Related Alteration in Serum Adiponectin in Rats and Its Association with Insulin Resistance Markers

2019 ◽  
Author(s):  
Marziyeh Feyzi ◽  
Mohammad Reza Tabandeh ◽  
Mehrdad Shariati ◽  
Mohammad Amin Edalatmanesh
Keyword(s):  
Insulin Resistance ◽  
Male Rats ◽  
Serum Adiponectin ◽  
Oral Glucose ◽  
Dependent Manner ◽  
Age Progression ◽  
Age Related ◽  
Glucose Ingestion ◽  
Age Dependent ◽  
Old Rats

Introduction: Adiponectin is one of the most important adipose derived hormone that conflicting data are available about serum changes of adiponectin at different ages.The present study was done to determine the age related changes in serum adiponectin and its association with insulin resistance (IR) indices in aging in male rats. Methods: In this study, serum samples were obtained from male rats at different ages, including 2, 5, 10, 18, 52 and 72 weeks age (n=10 in each age group). Oral glucose tolerance and glucose stimulated insulin secretion tests were measured using determination of glucose concentrations at 15, 30, 45 and 60 min after oral ingestion of glucose (1 mg/kg body weight) for each animal. Serum adiponectin and insulin levels were determined using species specific ELISA kits. HOMA-IR was calculated based on glucose and insulin concentrations. Data were analyzed using SPSS version 16 software (SPSS Inc., Chicago, IL) also using one way analysis of variance and LSD posthoc tests. Results: Our results showed an age dependent decrease in serum adiponectin concentration, and 72-week old rats had the lowest level of adiponectin compared with those in other ages (p<0.05). IR indices, including fasting glucose, insulin, HOMA-IR and response to oral glucose ingestion was increased in an age dependent manner and 72-week old rats showed the highest levels of the IR indices. Conclusion: Regarding the role of adiponectin in glucose homeostasis and insulin sensitization, it seems that reduction of serum adiponectin with age progression may be an important mechanism of insulin resistance in aging.

scholarly journals Mitochondrial Aging and Age-Related Dysfunction of Mitochondria

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Dimitry A. Chistiakov ◽  
Igor A. Sobenin ◽  
Victor V. Revin ◽  
Alexander N. Orekhov ◽  
Yuri V. Bobryshev
Keyword(s):  
Mitochondrial Function ◽  
Antioxidant Defense ◽  
Mitochondrial Dynamics ◽  
Oxidative Capacity ◽  
Ros Generation ◽  
Atp Production ◽  
Age Related ◽  
Related Phenotype ◽  
Age Dependent ◽  
Aged Subjects

Age-related changes in mitochondria are associated with decline in mitochondrial function. With advanced age, mitochondrial DNA volume, integrity and functionality decrease due to accumulation of mutations and oxidative damage induced by reactive oxygen species (ROS). In aged subjects, mitochondria are characterized by impaired function such as lowered oxidative capacity, reduced oxidative phosphorylation, decreased ATP production, significant increase in ROS generation, and diminished antioxidant defense. Mitochondrial biogenesis declines with age due to alterations in mitochondrial dynamics and inhibition of mitophagy, an autophagy process that removes dysfunctional mitochondria. Age-dependent abnormalities in mitochondrial quality control further weaken and impair mitochondrial function. In aged tissues, enhanced mitochondria-mediated apoptosis contributes to an increase in the percentage of apoptotic cells. However, implementation of strategies such as caloric restriction and regular physical training may delay mitochondrial aging and attenuate the age-related phenotype in humans.

Age-related Changes in Brain Regional Activity during Chewing: A Functional Magnetic Resonance Imaging Study

2003 ◽  
Vol 82 (8) ◽  
pp. 657-660 ◽  
Author(s):  
M. Onozuka ◽  
M. Fujita ◽  
K. Watanabe ◽  
Y. Hirano ◽  
M. Niwa ◽  
...  
Keyword(s):  
Neuronal Activity ◽  
Dependent Manner ◽  
Prefrontal Area ◽  
Gum Chewing ◽  
Regional Activity ◽  
Healthy Humans ◽  
Age Related ◽  
Age Dependent ◽  
The Right ◽  
Age Related Changes

Age-related changes in mastication-induced brain neuronal activity have been suggested. However, in humans, little is known about the anatomical regions involved. Using fMRI during cycles of rhythmic gum-chewing and no chewing, we have examined the effect of aging on brain regional activity during chewing in young adult (19–26 yrs), middle-aged (42–55 yrs), and aged (65–73 yrs) healthy humans. In all subjects, chewing resulted in a bilateral increase in the BOLD signals in the sensorimotor cortex, cerebellum, thalamus, supplementary motor area, and insula, and a unilateral increase in the right prefrontal area. In the first three regions, the signal increases were attenuated in an age-dependent manner, whereas, in the right prefrontal area, the converse was seen. The remaining two regions showed no significant differences with ages. These results indicate that chewing causes regional increases in neuronal activity in the brain, some of which are age-dependent.

scholarly journals Changes in Locomotor Activity and Oxidative Stress-Related Factors after the Administration of an Amino Acid Mixture by Generation and Age

2021 ◽  
Vol 22 (18) ◽  
pp. 9822
Author(s):  
Yejin Ahn ◽  
Ki-Bae Hong ◽  
Suhyeon Kim ◽  
Hyung Joo Suh ◽  
Kyungae Jo
Keyword(s):  
Oxidative Stress ◽  
Sleep Time ◽  
Behavioral Changes ◽  
Acid Mixture ◽  
Dependent Manner ◽  
Reaction Products ◽  
Related Factors ◽  
Age Related ◽  
Age Dependent ◽  
And Oxidative Stress

Amino acids, as nutrients, are expected to improve sleep disorders. This study aimed to evaluate the generation- and age-dependent sleep-improving effects of γ-aminobutyric acid (GABA) and 5-hydroxytryptophan (5-HTP) coadministration. The differentially expressed genes and generation-related behavior after the administration of a GABA/5-HTP mixture were measured in a Drosophila model, while age-related changes in gene expression and oxidative stress-related parameters were measured in a mouse model. The GABA/5-HTP-treated group showed significant behavioral changes compared to the other groups. Sequencing revealed that the GABA/5-HTP mixture influenced changes in nervous system-related genes, including those involved in the regulation of the expression of behavioral and synaptic genes. Additionally, total sleep time increased with age, and nighttime sleep time in the first- and third-generation flies was significantly different from that of the control groups. The GABA/5-HTP mixture induced significant changes in the expression of sleep-related receptors in both models. Furthermore, the GABA/5-HTP mixture reduced levels of ROS and ROS reaction products in an age-dependent manner. Therefore, the increase in behavioral changes caused by GABA/5-HTP mixture administration was effective in eliminating ROS activity across generations and ages.

scholarly journals Dendranthema zawadskii var. lucidum (Nakai) J.H. Park Extract Inhibits Cellular Senescence in Human Dermal Fibroblasts and Aging-Related Inflammation in Rats

Processes ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 801
Author(s):  
Jehun Choi ◽  
Gwi-Yeong Jang ◽  
Jeonghoon Lee ◽  
Hae-Young Chung ◽  
Hyung-Jun Noh ◽  
...  
Keyword(s):  
Cellular Senescence ◽  
Cell Cycle Progression ◽  
Inflammatory Responses ◽  
Dermal Fibroblast ◽  
Dermal Fibroblasts ◽  
Dependent Manner ◽  
Aged Rats ◽  
Age Related ◽  
Dendranthema Zawadskii ◽  
Beta Galactosidase

Senescence is the phenomenon by which physiological functions of organisms degenerate with time. Cellular senescence is marked by an inhibition of cell cycle progression. Beta-galactosidase accumulates in the lysosomes of aged cells. In this study, human dermal fibroblast cells (HDFs) were treated with 0.5 μM doxorubicin for 4 h to induce cellular senescence. Senescence-associated beta-galactosidase (SA-β-gal) activity was then measured 72 h after treatment with aerial parts of Dendranthema zawadskii var. lucidum (Nakai) J.H. Park (DZ) extract. Treatment with DZ extract significantly decreased SA-β-gal activity in a dose-dependent manner in HDFs. Additionally, DZ extract treatment reduced age-related oxidative stress and inflammation in the aortas of aged rats. The reactive oxygen species (ROS) levels in aortas of aged control rats were higher than those in young rats. However, DZ extract-fed aged rats showed significantly lower ROS levels than the aged control rats. When the aged rats were treated with DZ extract at either 0.2 or 1.0 mg∙kg−1∙day−1, NF-κB levels in aorta tissue decreased significantly compared to those in aorta tissue of the aged control rats without DZ treatment. In addition, DZ extract-fed aged rat aortas showed significant reductions in expression of iNOS and COX-2 induced by NF-κB translocation. Therefore, these results suggest that DZ effectively inhibited senescence-related NF-κB activation and inflammation. DZ extract may have a role in the prevention of the vascular inflammatory responses that occur during vascular aging.

scholarly journals Loss-of-function of p53 isoform Δ113p53 accelerates brain aging in zebrafish

2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Ting Zhao ◽  
Shengfan Ye ◽  
Zimu Tang ◽  
Liwei Guo ◽  
Zhipeng Ma ◽  
...  
Keyword(s):  
Replicative Senescence ◽  
Brain Aging ◽  
Ventricular Zone ◽  
Human Fibroblasts ◽  
Cell Lineage ◽  
Lineage Tracing ◽  
Dependent Manner ◽  
Loss Of Function ◽  
Antioxidant Genes ◽  
Age Related

AbstractReactive oxygen species (ROS) stress has been demonstrated as potentially critical for induction and maintenance of cellular senescence, and been considered as a contributing factor in aging and in various neurological disorders including Alzheimer’s disease (AD) and amyotrophic lateral sclerosis (ALS). In response to low-level ROS stress, the expression of Δ133p53, a human p53 isoform, is upregulated to promote cell survival and protect cells from senescence by enhancing the expression of antioxidant genes. In normal conditions, the basal expression of Δ133p53 prevents human fibroblasts, T lymphocytes, and astrocytes from replicative senescence. It has been also found that brain tissues from AD and ALS patients showed decreased Δ133p53 expression. However, it is uncharacterized if Δ133p53 plays a role in brain aging. Here, we report that zebrafish Δ113p53, an ortholog of human Δ133p53, mainly expressed in some of the radial glial cells along the telencephalon ventricular zone in a full-length p53-dependent manner. EDU-labeling and cell lineage tracing showed that Δ113p53-positive cells underwent cell proliferation to contribute to the neuron renewal process. Importantly, Δ113p53M/M mutant telencephalon possessed less proliferation cells and more senescent cells compared to wild-type (WT) zebrafish telencephalon since 9-months old, which was associated with decreased antioxidant genes expression and increased level of ROS in the mutant telencephalon. More interestingly, unlike the mutant fish at 5-months old with cognition ability, Δ113p53M/M zebrafish, but not WT zebrafish, lost their learning and memory ability at 19-months old. The results demonstrate that Δ113p53 protects the brain from aging by its antioxidant function. Our finding provides evidence at the organism level to show that depletion of Δ113p53/Δ133p53 may result in long-term ROS stress, and finally lead to age-related diseases, such as AD and ALS in humans.

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 Identification of Withania somnifera-Silybum marianum-Trigonella foenum-graecum Formulation as a Nutritional Supplement to Contrast Muscle Atrophy and Sarcopenia

Nutrients ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 49
Author(s):  
Laura Salvadori ◽  
Manuela Mandrone ◽  
Tommaso Manenti ◽  
Catia Ercolani ◽  
Luca Cornioli ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Muscle Mass ◽  
Muscle Atrophy ◽  
Withania Somnifera ◽  
Myoblast Differentiation ◽  
C2c12 Myotubes ◽  
Silybum Marianum ◽  
Trigonella Foenum Graecum ◽  
Age Related

Background: Muscle atrophy, i.e., the loss of skeletal muscle mass and function, is an unresolved problem associated with aging (sarcopenia) and several pathological conditions. The imbalance between myofibrillary protein breakdown (especially the adult isoforms of myosin heavy chain, MyHC) and synthesis, and the reduction of muscle regenerative potential are main causes of muscle atrophy. Methods: Starting from one-hundred dried hydroalcoholic extracts of medical plants, we identified those able to contrast the reduction of C2C12 myotube diameter in well-characterized in vitro models mimicking muscle atrophy associated to inflammatory states, glucocorticoid treatment or nutrient deprivation. Based on their ability to rescue type II MyHC (MyHC-II) expression in atrophying conditions, six extracts with different phytochemical profiles were selected, mixed in groups of three, and tested on atrophic myotubes. The molecular mechanism underpinning the effects of the most efficacious formulation, and its efficacy on myotubes obtained from muscle biopsies of young and sarcopenic subjects were also investigated. Results: We identified WST (Withania somnifera, Silybum marianum, Trigonella foenum-graecum) formulation as extremely efficacious in protecting C2C12 myotubes against MyHC-II degradation by stimulating Akt (protein kinase B)-dependent protein synthesis and p38 MAPK (p38 mitogen-activated protein kinase)/myogenin-dependent myoblast differentiation. WST sustains trophism in C2C12 and young myotubes, and rescues the size, developmental MyHC expression and myoblast fusion in sarcopenic myotubes. Conclusion: WST strongly counteracts muscle atrophy associated to different conditions in vitro. The future validation in vivo of our results might lead to the use of WST as a food supplement to sustain muscle mass in diffuse atrophying conditions, and to reverse the age-related functional decline of human muscles, thus improving people quality of life and reducing social and health-care costs.

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