Proteomics analysis provides insight into caloric restriction mediated oxidation and expression of brain proteins associated with age-related impaired cellular processes: Mitochondrial dysfunction, glutamate dysregulation and impaired protein synthesis

2006 ◽  
Vol 27 (7) ◽  
pp. 1020-1034 ◽  
Author(s):  
H. Fai Poon ◽  
Holly M. Shepherd ◽  
Tanea T. Reed ◽  
Vittorio Calabrese ◽  
Anna-Maria Giuffrida Stella ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Mitochondrial Dysfunction ◽  
Caloric Restriction ◽  
Proteomics Analysis ◽  
Brain Proteins ◽  
Cellular Processes ◽  
Age Related ◽  
Mediated Oxidation ◽  
Insight Into

An Insight Into Mitochondrial Dysfunction and its Implications in Neuro-logical Diseases

2020 ◽  
Vol 22 ◽  
Author(s):  
Asimul Islam ◽  
Anas Shamsi ◽  
Rashid Waseem ◽  
Syed Kazim
Keyword(s):  
Mitochondrial Dysfunction ◽  
Neurodegenerative Disorders ◽  
Large Body ◽  
Ros Generation ◽  
Cell Organelles ◽  
Ischemic Brain ◽  
Cellular Processes ◽  
Vital Cell ◽  
Insight Into

Abstract:: In the last few years, a massive increase in the research has been observed that focusses on investigating the role of mitochondria in pathogenesis of several neurodegenerative disorders. Mitochondria are vital cell organelles having im-portant roles in different cellular processes including energy production, calcium signaling, ROS generation, apoptosis, etc. Therefore, healthy mitochondria are necessary for cell survival and functioning. It would seem feasible that mitochondrial dysfunction will have implications in various pathological conditions. A large body of evidence indicates the role of mito-chondrion as a potential key player in the loss or dysfunction of neurons in various neurodegenerative disorders. In this review, we provide an insight into the mitochondrial dysfunction and its involvement in the pathology of several neurolog-ical diseases such as Alzheimer’s disease, Parkinson’s disease, Amyotrophic Lateral Sclerosis, Hypoxic-Ischemic Brain Injury and many more.

scholarly journals A Single Cell Transcriptomic Atlas Characterizes Aging Tissues in the Mouse

2019 ◽  
Author(s):  
◽  
Angela Oliveira Pisco ◽  
Aaron McGeever ◽  
Nicholas Schaum ◽  
Jim Karkanias ◽  
...  
Keyword(s):  
Single Cell ◽  
Cell Types ◽  
Cell Type ◽  
Cellular Processes ◽  
Progressive Loss ◽  
Age Related ◽  
Multiple Cell ◽  
Cell Type Specific ◽  
Molecular Information ◽  
Insight Into

AbstractAging is characterized by a progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death1. Despite rapid advances over recent years, many of the molecular and cellular processes which underlie progressive loss of healthy physiology are poorly understood2. To gain a better insight into these processes we have created a single cell transcriptomic atlas across the life span of Mus musculus which includes data from 23 tissues and organs. We discovered cell-specific changes occurring across multiple cell types and organs, as well as age related changes in the cellular composition of different organs. Using single-cell transcriptomic data we were able to assess cell type specific manifestations of different hallmarks of aging, such as senescence3, genomic instability4 and changes in the organism’s immune system2. This Tabula Muris Senis provides a wealth of new molecular information about how the most significant hallmarks of aging are reflected in a broad range of tissues and cell types.

Cardiac mitochondrial bioenergetics, oxidative stress, and aging

2007 ◽  
Vol 292 (6) ◽  
pp. C1983-C1992 ◽  
Author(s):  
Sharon Judge ◽  
Christiaan Leeuwenburgh
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dysfunction ◽  
Caloric Restriction ◽  
Critical Role ◽  
Antioxidant Enzyme Activities ◽  
Theories Of Aging ◽  
Age Related ◽  
Interfibrillar Mitochondria ◽  
Oxidant Production ◽  
Subsarcolemmal Mitochondria

Mitochondria have been a central focus of several theories of aging as a result of their critical role in bioenergetics, oxidant production, and regulation of cell death. A decline in cardiac mitochondrial function coupled with the accumulation of oxidative damage to macromolecules may be causal to the decline in cardiac performance with age. In contrast, regular physical activity and lifelong caloric restriction can prevent oxidative stress, delay the onset of morbidity, increase life span, and reduce the risk of developing several pathological conditions. The health benefits of life long exercise and caloric restriction may be, at least partially, due to a reduction in the chronic amount of mitochondrial oxidant production. In addition, the available data suggest that chronic exercise may serve to enhance antioxidant enzyme activities, and augment certain repair/removal pathways, thereby reducing the amount of oxidative tissue damage. However, the characterization of age-related changes to cardiac mitochondria has been complicated by the fact that two distinct populations of mitochondria exist in the myocardium: subsarcolemmal mitochondria and interfibrillar mitochondria. Several studies now suggest the importance of studying both mitochondrial populations when attempting to elucidate the contribution of mitochondrial dysfunction to myocardial aging. The role that mitochondrial dysfunction and oxidative stress play in contributing to cardiac aging will be discussed along with the use of lifelong exercise and calorie restriction as countermeasures to aging.

scholarly journals Phytochemical Nrf2 activator attenuates skeletal muscle mitochondrial dysfunction and impaired proteostasis in a preclinical model of musculoskeletal aging

2021 ◽  
Author(s):  
Robert V Musci ◽  
Kendra M Andrie ◽  
Maureen A Walsh ◽  
Zackary J Valenti ◽  
Maryam F Afzali ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Function ◽  
Guinea Pigs ◽  
Muscle Protein ◽  
System Capacity ◽  
Related Factor ◽  
Age Related ◽  
Nrf2 Activator

Musculoskeletal dysfunction is an age-related syndrome associated with impaired mitochondrial function and proteostasis. However, few interventions have tested targeting two drivers of musculoskeletal decline. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that stimulates transcription of cytoprotective genes and improves mitochondrial function. We hypothesized daily treatment with a Nrf2 activator in Hartley guinea pigs, a model of age-related musculoskeletal dysfunction, attenuates the progression of skeletal muscle mitochondrial dysfunction and impaired proteostasis, preserving musculoskeletal function. We treated 2-month- and 5-month-old male and female Hartley guinea pigs for 3 and 10 months, respectively, with the phytochemical Nrf2 activator PB125 (Nrf2a). Longitudinal assessments of voluntary mobility were measured using Any-Maze™ open-field enclosure monitoring. Cumulative skeletal muscle protein synthesis rates were measured using deuterium oxide over the final 30 days of treatment. Mitochondrial oxygen consumption in permeabilized soleus muscles was measured using ex vivo high resolution respirometry. In both sexes, Nrf2a 1) increased electron transfer system capacity; 2) attenuated the disease/age-related decline in coupled and uncoupled mitochondrial respiration; and 3) attenuated declines in protein synthesis in the myofibrillar, mitochondrial, and cytosolic subfractions of the soleus. These improvements were not associated with statistically significant prolonged maintenance of voluntary mobility in guinea pigs. Collectively, these results demonstrate that treatment with an oral Nrf2 activator contributes to maintenance of skeletal muscle mitochondrial function and proteostasis in a pre-clinical model of musculoskeletal decline. Further investigation is necessary to determine if these improvements are also accompanied by slowed progression of other aspects of musculoskeletal decline.

scholarly journals Impact of Caloric Restriction on Molecular and Functional Networks in Rhesus Monkeys

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 116-116
Author(s):  
Rozalyn Anderson
Keyword(s):  
Caloric Restriction ◽  
Rhesus Monkeys ◽  
Large Scale ◽  
Functional Networks ◽  
Functional Changes ◽  
Cellular Processes ◽  
Metabolic Component ◽  
Diverse Species ◽  
Age Related ◽  
Regulation Of Metabolism

Abstract Caloric restriction (CR) delays aging and the onset of age-related disease in diverse species. Several diseases of aging including diabetes, cancer, and neurodegeneration, have an established metabolic component. Although the mechanisms of CR remain unknown, numerous factors implicated in longevity regulation by CR converge on regulation of metabolism. The reprograming of metabolism with CR is tissue specific, but mitochondrial activation and changes in redox metabolism are among the shared features. Changes in non-coding miRNA and in processing of transcripts are contributing mechanisms in integrating metabolic and growth pathways. Our studies in simple cell culture shows that small changes in metabolic status can precipitate large-scale multi-modal functional changes across cellular processes. We propose that modest failures in metabolic integrity with age broadly impact homeostasis and adaptation, creating shared vulnerability to diseases and conditions despite differences in their etiology, and that CR harnesses this same axis to promote health and enhanced longevity.

Spatial localization of unknown proteins in the endoplasmic reticulum predicts functions

2007 ◽  
Vol 30 (4) ◽  
pp. 84
Author(s):  
Michael D. Jain ◽  
Hisao Nagaya ◽  
Annalyn Gilchrist ◽  
Miroslaw Cygler ◽  
John J.M. Bergeron
Keyword(s):  
Endoplasmic Reticulum ◽  
Protein Folding ◽  
Protein Synthesis ◽  
Protein Function ◽  
Protein Translocation ◽  
Spatial Localization ◽  
Predict Protein Function ◽  
Insight Into ◽  
Soluble Fractions ◽  
Er Membrane

Protein synthesis, folding and degradation functions are spatially segregated in the endoplasmic reticulum (ER) with respect to the membrane and the ribosome (rough and smooth ER). Interrogation of a proteomics resource characterizing rough and smooth ER membranes subfractionated into cytosolic, membrane, and soluble fractions gives a spatial map of known proteins involved in ER function. The spatial localization of 224 identified unknown proteins in the ER is predicted to give insight into their function. Here we provide evidence that the proteomics resource accurately predicts the function of new proteins involved in protein synthesis (nudilin), protein translocation across the ER membrane (nicalin), co-translational protein folding (stexin), and distal protein folding in the lumen of the ER (erlin-1, TMX2). Proteomics provides the spatial localization of proteins and can be used to accurately predict protein function.

scholarly journals DNA methylation differs extensively between strains of the same geographical origin and changes with age in Daphnia magna

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Jack Hearn ◽  
Fiona Plenderleith ◽  
Tom J. Little
Keyword(s):  
Dna Methylation ◽  
Caloric Restriction ◽  
Daphnia Magna ◽  
Single Gene ◽  
Methylation Status ◽  
Strain Differences ◽  
Life History Trait ◽  
Food Level ◽  
Epigenetic Clock ◽  
Age Related

Abstract Background Patterns of methylation influence lifespan, but methylation and lifespan may also depend on diet, or differ between genotypes. Prior to this study, interactions between diet and genotype have not been explored together to determine their influence on methylation. The invertebrate Daphnia magna is an excellent choice for testing the epigenetic response to the environment: parthenogenetic offspring are identical to their siblings (making for powerful genetic comparisons), they are relatively short lived and have well-characterised inter-strain life-history trait differences. We performed a survival analysis in response to caloric restriction and then undertook a 47-replicate experiment testing the DNA methylation response to ageing and caloric restriction of two strains of D. magna. Results Methylated cytosines (CpGs) were most prevalent in exons two to five of gene bodies. One strain exhibited a significantly increased lifespan in response to caloric restriction, but there was no effect of food-level CpG methylation status. Inter-strain differences dominated the methylation experiment with over 15,000 differently methylated CpGs. One gene, Me31b, was hypermethylated extensively in one strain and is a key regulator of embryonic expression. Sixty-one CpGs were differentially methylated between young and old individuals, including multiple CpGs within the histone H3 gene, which were hypermethylated in old individuals. Across all age-related CpGs, we identified a set that are highly correlated with chronological age. Conclusions Methylated cytosines are concentrated in early exons of gene sequences indicative of a directed, non-random, process despite the low overall DNA methylation percentage in this species. We identify no effect of caloric restriction on DNA methylation, contrary to our previous results, and established impacts of caloric restriction on phenotype and gene expression. We propose our approach here is more robust in invertebrates given genome-wide CpG distributions. For both strain and ageing, a single gene emerges as differentially methylated that for each factor could have widespread phenotypic effects. Our data showed the potential for an epigenetic clock at a subset of age positions, which is exciting but requires confirmation.

scholarly journals Role of amyloid β-peptide in the pathogenesis of age-related macular degeneration

2021 ◽  
Vol 6 (1) ◽  
pp. e000774
Author(s):  
Minwei Wang ◽  
Shiqi Su ◽  
Shaoyun Jiang ◽  
Xinghuai Sun ◽  
Jiantao Wang
Keyword(s):  
Mitochondrial Dysfunction ◽  
Macular Degeneration ◽  
Vision Loss ◽  
Cell Structure ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Amyloid Β ◽  
Age Related Macular Degeneration ◽  
Amyloid Β Peptide ◽  
Age Related

Age-related macular degeneration (AMD) is the most common eye disease in elderly patients, which could lead to irreversible vision loss and blindness. Increasing evidence indicates that amyloid β-peptide (Aβ) might be associated with the pathogenesis of AMD. In this review, we would like to summarise the current findings in this field. The literature search was done from 1995 to Feb, 2021 with following keywords, ‘Amyloid β-peptide and age-related macular degeneration’, ‘Inflammation and age-related macular degeneration’, ‘Angiogenesis and age-related macular degeneration’, ‘Actin cytoskeleton and amyloid β-peptide’, ‘Mitochondrial dysfunction and amyloid β-peptide’, ‘Ribosomal dysregulation and amyloid β-peptide’ using search engines Pubmed, Google Scholar and Web of Science. Aβ congregates in subretinal drusen of patients with AMD and participates in the pathogenesis of AMD through enhancing inflammatory activity, inducing mitochondrial dysfunction, altering ribosomal function, regulating the lysosomal pathway, affecting RNA splicing, modulating angiogenesis and modifying cell structure in AMD. The methods targeting Aβ are shown to inhibit inflammatory signalling pathway and restore the function of retinal pigment epithelium cells and photoreceptor cells in the subretinal region. Targeting Aβ may provide a novel therapeutic strategy for AMD.

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