scholarly journals Multidimensional Proteomics Identifies Declines in Protein Homeostasis and Mitochondria as Early Signals for Normal Aging and Age-associated Disease in Drosophila

2019 ◽  
Vol 18 (10) ◽  
pp. 2078-2088 ◽  
Author(s):  
Lu Yang ◽  
Ye Cao ◽  
Jing Zhao ◽  
Yanshan Fang ◽  
Nan Liu ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Protein Dynamics ◽  
Isotope Labeling ◽  
Specific Protein ◽  
Normal Aging ◽  
Protein Homeostasis ◽  
Age Related ◽  
Muscle Tissues ◽  
Proteomic Study ◽  
Related Proteins

Aging is characterized by a gradual deterioration in proteome. However, how protein dynamics that changes with normal aging and in disease is less well understood. Here, we profiled the snapshots of aging proteome in Drosophila, from head and muscle tissues of post-mitotic somatic cells, and the testis of mitotically-active cells. Our data demonstrated that dysregulation of proteome homeostasis, or proteostasis, might be a common feature associated with age. We further used pulsed metabolic stable isotope labeling analysis to characterize protein synthesis. Interestingly, this study determined an age-modulated decline in protein synthesis with age, particularly in the pathways related to mitochondria, neurotransmission, and proteostasis. Importantly, this decline became dramatically accelerated in Pink1 mutants, a Drosophila model of human age-related Parkinson's disease. Taken together, our multidimensional proteomic study revealed tissue-specific protein dynamics with age, highlighting mitochondrial and proteostasis-related proteins. We suggest that declines in proteostasis and mitochondria early in life are critical signals prior to the onset of aging and aging-associated diseases.

scholarly journals Location, location, location: subcellular protein partitioning in proteostasis and aging

2021 ◽  
Author(s):  
Anita V. Kumar ◽  
Louis R. Lapierre
Keyword(s):  
Quality Control ◽  
Protein Folding ◽  
Protein Synthesis ◽  
Cell Survival ◽  
Recent Literature ◽  
Protein Homeostasis ◽  
Control Mechanisms ◽  
Somatic Maintenance ◽  
Age Related ◽  
Protein Partitioning

AbstractSomatic maintenance and cell survival rely on proper protein homeostasis to ensure reliable functions across the cell and to prevent proteome collapse. Maintaining protein folding and solubility is central to proteostasis and is coordinated by protein synthesis, chaperoning, and degradation capacities. An emerging aspect that influences proteostasis is the dynamic protein partitioning across different subcellular structures and compartments. Here, we review recent literature related to nucleocytoplasmic partitioning of proteins, nuclear and cytoplasmic quality control mechanisms, and their impact on the development of age-related diseases. We also highlight new points of entry to modulate spatially-regulated proteostatic mechanisms to delay aging.

scholarly journals The ATP Synthase Deficiency in Human Diseases

Life ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 325
Author(s):  
Chiara Galber ◽  
Stefania Carissimi ◽  
Alessandra Baracca ◽  
Valentina Giorgio
Keyword(s):  
Oxidative Phosphorylation ◽  
Atp Synthase ◽  
Mitochondrial Protein ◽  
High Energy ◽  
Neurocognitive Disorders ◽  
Human Diseases ◽  
Age Related ◽  
Muscle Tissues ◽  
Mitochondrial Atp Synthase ◽  
Genes Encoding

Human diseases range from gene-associated to gene-non-associated disorders, including age-related diseases, neurodegenerative, neuromuscular, cardiovascular, diabetic diseases, neurocognitive disorders and cancer. Mitochondria participate to the cascades of pathogenic events leading to the onset and progression of these diseases independently of their association to mutations of genes encoding mitochondrial protein. Under physiological conditions, the mitochondrial ATP synthase provides the most energy of the cell via the oxidative phosphorylation. Alterations of oxidative phosphorylation mainly affect the tissues characterized by a high-energy metabolism, such as nervous, cardiac and skeletal muscle tissues. In this review, we focus on human diseases caused by altered expressions of ATP synthase genes of both mitochondrial and nuclear origin. Moreover, we describe the contribution of ATP synthase to the pathophysiological mechanisms of other human diseases such as cardiovascular, neurodegenerative diseases or neurocognitive disorders.

scholarly journals Sex-Specific Differences in Extracellular Vesicle Protein Cargo in Synovial Fluid of Patients with Osteoarthritis

Life ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 337
Author(s):  
Ravindra Kolhe ◽  
Virgenal Owens ◽  
Ashok Sharma ◽  
Tae Jin Lee ◽  
Wenbo Zhi ◽  
...  
Keyword(s):  
Synovial Fluid ◽  
Protein Content ◽  
Extracellular Vesicle ◽  
Specific Protein ◽  
Paracrine Signaling ◽  
Age Related ◽  
Specific Manner ◽  
Inflammatory Processes ◽  
Novel Biomarkers ◽  
Cellular Pathways

Women are at a significantly higher risk of developing osteoarthritis (OA) compared to males. The pathogenesis of osteoarthritis (OA) in women is poorly understood. Extracellular vesicles (EVs) have been shown to play an essential role in numerous signaling processes during the pathogenesis of age-related diseases via paracrine signaling. Molecular profiling of the synovial fluid-derived EVs cargo in women may help in the discovery of novel biomarkers and therapeutics for the treatment of OA in women. Previously, we reported that synovial fluid-derived EV miRNA cargo differs in a sex-specific manner. This study aims to characterize synovial fluid-derived EV protein cargo in OA patients. Our data showed sex-specific EVs protein content in OA. We found haptoglobin, orosomucoid, and ceruloplasmin significantly up-regulated, whereas apolipoprotein down-regulated in female OA EVs. In males, we discovered β-2-glycoprotein, and complement component 5 proteins significantly up-regulated and Spt-Ada-Gcn5 acetyltransferase (SAGA)-associated factor 29 down-regulated in male OA EVs. Database for Annotation, Visualization, and Integrated Discovery (DAVID) and QuickGO analysis revealed OA-specific protein involvement in several biological, molecular, and cellular pathways, specifically in inflammatory processes. In conclusion, synovial fluid EV protein content is altered in a sex-specific manner with OA, explaining the increased prevalence and severity of OA in women.

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.

Influence of Neurosecretory Cells and of Corpus Allatum on Intestinal Protease Activity in the Adult Calliphora Erythrocephala MEIG

1963 ◽  
Vol 40 (2) ◽  
pp. 301-321
Author(s):  
ELLEN THOMSEN ◽  
IB MØLLER
Keyword(s):  
Protein Synthesis ◽  
Protease Activity ◽  
Proteolytic Enzymes ◽  
Specific Protein ◽  
Neurosecretory Cells ◽  
Corpus Allatum ◽  
Minor Effect ◽  
Calliphora Erythrocephala ◽  
Sugar Water ◽  
The Mean

1. The protease activity of the adult Calliphora female measured on the first 5 days after emergence was found to be highly influenced by the diet, the activity of females fed on sugar, water and meat (meat-flies) being much higher than that of females fed only on sugar and water (sugar-flies). 2. The development of the enzyme(s) was found to be controlled by the medial neurosecretory cells (m.n.c.), the mean protease activity of females deprived of their m.n.c. only amounting to one-quarter to one-third of the maximum values for the meat-flies. 3. Implantation of corpora cardiaca-allata (presumably containing m.n.c. hormone) into females without m.n.c. raised the protease activity of these significantly, showing that the influence of the implanted organs must be hormonal. 4. The corpus allatum was found to have a certain, if minor, effect on the protease activity. 5. It is concluded that in Calliphora the eating of meat exerts its effect on the production of protease mainly indirectly by causing liberation of m.n.c. hormone into the blood. 6. As proteases are themselves proteins, the effect of the m.n.c. hormone on the production of proteolytic enzymes by the gut cells must be regarded as an effect on the specific protein synthesis of these cells. There is some evidence that the m.n.c. hormone might be involved in the regulation of protein synthesis in general.

The initial synthesis of haemoglobin in de-embryonated chick blastoderms.

Development ◽  
1964 ◽  
Vol 12 (4) ◽  
pp. 609-619
Author(s):  
Anna Hell
Keyword(s):  
Protein Synthesis ◽  
Deoxyribonucleic Acid ◽  
Primitive Streak ◽  
Specific Protein ◽  
In Vitro System ◽  
Embryonic Tissues ◽  
Different Types ◽  
Excellent Tool ◽  
Made In

Enormous progress has been made in the last few years towards the elucidation of the mechanism of protein synthesis, and great interest is centred on the steps leading to cellular differentiation and specific protein synthesis. We know that genetic information is passed on from one generation of cells to the next by deoxyribonucleic acid (DNA), and that this material directs all protein synthesis by the intermediary of the different types of ribonucleic acid (RNA). A simple in vitro system described by O'Brien (1959) seemed to offer an excellent tool for the study of the differentiation of the blood islands, and the initial formation of a well-known protein, haemoglobin (Hb), in chick embryonic tissues. After de-embryonation, chick blastoderms, from the stage of primitive streak onwards, can be cultured in vitro on a saline agar medium supplemented with glucose.

Scaphechinus mirabilis extract effectively inhibits the proliferation of BPH-1 and LNCaP prostate epithelial cells

2021 ◽  
Vol 11 ◽  
Author(s):  
Kyung-Hyun Kim ◽  
Geum-Lan Hong ◽  
Shanika Karunasagara ◽  
Ju-Young Jung
Keyword(s):  
Epithelial Cells ◽  
Sea Urchins ◽  
Specific Antigen ◽  
Marine Species ◽  
Lncap Cells ◽  
Caspase 9 ◽  
Scaphechinus Mirabilis ◽  
Age Related ◽  
Prostate Epithelial Cells ◽  
Related Proteins

Background: Benign prostatic hyperplasia (BPH) is an age-related disease characterized by progressive proliferation of prostate stromal and epithelial cells. While the precise etiology of BPH is still not clear, the proliferation of epithelial cells has been implicated in the development of the disease. Scaphechinus mirabilis (S. mirabilis) is a marine species belonging to the order Clypeasteroida, which contains flat, burrowing sea urchins. Objective: This study examined the effects of S. mirabilis extract on the proliferation of BPH-1 and LNCaP prostate epithelial cells. Methods: BPH-1 and LNCaP cells were cultured and treated with S. mirabilis extract (50, 100, and 200 μg/ml). The viability of cells treated with S. mirabilis extract was determined by the MTT assay. Results: Proliferation of BPH-1 and testosterone-induced LNCaP cells was inhibited by treatment with S. mirabilis extract. S. mirabilis extract suppressed the expression of androgen-related proteins, such as androgen receptor, prostate-specific antigen, and 5α-reductase 2. S. mirabilis extract inhibited testosterone-induced proliferation. Moreover, S. mirabilis extract induced apoptotic responses by regulating the expression of caspase-9, Bcl-2, and Bax. Conclusion: These findings suggest that S. mirabilis extract abrogated the expression of androgen-related proteins by inducing apoptotic responses, which could be valuable for the design of new therapeutic agents for the treatment of BPH.

Mechanism of Sequential Swallowing During Straw Drinking in Healthy Young and Older Adults

2004 ◽  
Vol 47 (1) ◽  
pp. 33-45 ◽  
Author(s):  
Stephanie K. Daniels ◽  
David M. Corey ◽  
Leslie D. Hadskey ◽  
Calli Legendre ◽  
Daniel H. Priestly ◽  
...  
Keyword(s):  
Older Adults ◽  
Young Adults ◽  
Movement Patterns ◽  
Leading Edge ◽  
Normal Aging ◽  
Significant Relation ◽  
Age Related ◽  
Laryngeal Penetration ◽  
Airway Invasion ◽  
Edge Location

Recent research has revealed differences between isolated and sequential swallowing in healthy young adults; however, the influence of normal aging on sequential swallowing has not been studied. Thus, the purpose of this investigation was to examine the effects of normal aging on deglutition during sequential straw drinking. Videofluoroscopic samples of two 10-s straw drinking trials were obtained for 20 healthy young men (age 29±3 years) and 18 healthy older men (age 69±7 years). Hyolaryngeal complex (HLC) movement patterns, leading edge of the bolus location at swallow onset, and occurrences of airway invasion were determined. Two HLC patterns were identified: (a) HLC lowering with the epiglottis returned to upright between swallows and (b) partially maintained HLC elevation with the epiglottis inverted between swallows. The bolus was frequently in the hypopharynx at swallow onset. Strong associations were identified between age and HLC pattern, age and leading edge of the bolus location, and HLC pattern and leading edge location. Laryngeal penetration was uncommon overall; however, it occurred more frequently in the older adults than in the young adults. A significant relation was identified between age and the average Penetration-Aspiration Scale score. Laryngeal penetration was associated with both HLC movement patterns and hypopharyngeal bolus location, particularly in older adults. Results indicate that subtle age-related differences are evident in healthy young and older adults with sequential straw drinking. These data suggest that specific inherent swallowing patterns may increase the risk of laryngeal penetration with normal aging.

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