Integrated Transcriptome, Proteome, Acetylome, and Metabolome Profiling of Mouse Liver During Normal Aging

Abstract BackgroundAging is a complex biological process accompanied by a time-dependent functional decline that affects most living organisms. We aimed to obtain an integrated aging-associated profile of the mouse liver using a multi-omics approach.ResultsWe performed a combined transcriptome, proteome, acetylome, and metabolome analysis of liver tissues from young and old mice under physiological conditions. Old mice were frequently obese with a fatty liver, and the observed profile changes in different omics were generally moderate. Specifically, transcriptome, proteome, and acetylome analyses revealed different patterns in old and young mice, but metabolome analysis did not. Functional enrichment analysis showed that metabolic pathways were broadly altered during normal aging. Notably, the genes, proteins, and metabolites involved in pyrimidine and glutathione metabolisms were significantly affected in all these four omics. Moreover, we observed increased arachidonic acid metabolism and decreased complement and coagulation cascades in old mice, suggesting an alteration in the immune function during normal aging.ConclusionsWe conducted a multi-omics investigation of normal liver aging in mice and generated comprehensive datasets for aging research. Further analysis revealed that impairment of pyrimidine and glutathione metabolisms and immune function may be critical for hepatic aging and may provide targets for aging interventions.

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Phosphoproteome Profiling of Mouse Liver During Normal Aging

10.21203/rs.3.rs-966762/v1 ◽

2021 ◽

Author(s):

Jiang-Feng Liu ◽

Yue Wu ◽

Ye-Hong Yang ◽

Song-Feng Wu ◽

Shu Liu ◽

...

Keyword(s):

Fatty Liver ◽

Fatty Acid Biosynthesis ◽

Interaction Analysis ◽

Functional Decline ◽

Normal Aging ◽

Functional Enrichment ◽

Differentially Expressed ◽

Secretory Process ◽

Complex Biological Process ◽

Old Mice

Abstract BackgroundAging is a complex biological process accompanied by a time-dependent functional decline that affects most living organisms. Omics studies help to comprehensively understand the mechanism of aging and discover potential intervention methods. Old mice were frequently obese with a fatty liver. MethodsWe applied mass spectrometry-based phosphoproteomics to obtain a global phosphorylation profile of liver in mice aged 2 or 18 months. A total of 5,685 phosphosites in 2,335 proteins were filtered for quantitative analysis. Phosphoproteome weakly separated young and old mice. ResultsCombining kinase prediction, kinase-substrate interaction analysis, and KEGG functional enrichment analysis, we observed high phosphorylation of fatty acid biosynthesis, b-oxidation, and potential secretory process, together with low phosphorylation of Egfr-Sos1-Araf/Braf-Map2k1-Mapk1 pathway and Ctnnb1 during aging. Proteins with differentially expressed phosphosites seemed more directly related to aging-associated fatty liver phenotype compared to the differentially expressed transcripts. Phosphoproteome may observe distinctive biological functions lost in transcriptome and proteome. ConclusionsIn summary, we constructed a phosphorylation-associated network in the liver of mice during normal aging, which may help to discover novel anti-aging strategies.

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The effect of age on protein synthesis in mouse liver

Biochemical Journal ◽

10.1042/bj1130869 ◽

1969 ◽

Vol 113 (5) ◽

pp. 869-878 ◽

Cited By ~ 103

Author(s):

W. I. P. Mainwaring

Keyword(s):

Messenger Rna ◽

Mouse Liver ◽

Direct Evidence ◽

Similar System ◽

Ribonucleoprotein Particles ◽

Polyuridylic Acid ◽

A Cell ◽

Rate Of Hydrolysis ◽

Old Mice ◽

Effect Of Age

1. A system of microsomes and 105000g supernatant from livers of old mice is less able to promote the incorporation of [14C]phenylalanine into protein than a similar system from livers of young animals. 2. The decrease in [14C]phenylalanine incorporation is attributable to changes in microsomes from old animals rather than in the cell-sap fraction. 3. Decreased synthetic ability is found in various classes of microsomes from older animals, namely unfractionated, light and heavy microsomes, but not in detergent-washed ribonucleoprotein particles. 4. Deletions of certain detergent-soluble microsomal proteins accompany the decreased synthetic ability of microsomes from older animals. 5. Microsomes from old mice are less responsive to a synthetic messenger RNA, polyuridylic acid, and this is partly due to a higher rate of hydrolysis in the presence of cell sap from animals of extreme age. 6. Other more direct evidence, from the priming of a cell-free protein-synthesizing system from bacteria and the examination of ribonucleoprotein particles on sucrose density gradients, suggests that senescence is accompanied by a decrease in messenger RNA content.

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CIDE-A is expressed in liver of old mice and in type 2 diabetic mouse liver exhibiting steatosis

Comparative Hepatology ◽

10.1186/1476-5926-6-4 ◽

2007 ◽

Vol 6 (1) ◽

Cited By ~ 19

Author(s):

Bruce Kelder ◽

Keith Boyce ◽

Andres Kriete ◽

Ryan Clark ◽

Darlene E Berryman ◽

...

Keyword(s):

Mouse Liver ◽

Diabetic Mouse ◽

Old Mice ◽

Type 2 Diabetic

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Resveratrol: A Sirtuin Activator and The Fountain of Youth

The Indonesian Biomedical Journal ◽

10.18585/inabj.v7i1.16 ◽

2015 ◽

Vol 7 (1) ◽

pp. 1 ◽

Cited By ~ 1

Author(s):

Anna Meiliana ◽

Nurrani Mustika Dewi ◽

Andi Wijaya

Keyword(s):

Caloric Restriction ◽

Healthy Aging ◽

Myocardial Infarct ◽

Functional Decline ◽

Steady Increase ◽

Healthy Human ◽

Aging Research ◽

Human Lifespan ◽

Age Related ◽

Fountain Of Youth

BACKGROUND: An organism’s lifespan is inevitably accompanied by the aging process, which involves functional decline, a steady increase of a plethora of chronic diseases, and ultimately death. Thus, it has been an ongoing dream of mankind to improve healthspan and extend life.CONTENT: There are only a few proposed aging interventions: caloric restriction, exercise, and the use of low-molecular-weight compounds, including spermidine, metformin, resveratrol, and rapamycin. Resveratrol, a constituent of red wine, has long been suspected to have cardioprotective effects. Interest in this compound has been renewed in recent years, first from its identification as a chemopreventive agent for skin cancer, and subsequently from reports that it activates sirtuin deacetylases and extends the lifespans of lower organisms. Resveratrol have been shown to prevent and reduce the severity of age-related diseases such as atherosclerosis, stroke, myocardial infarct, diabetes, neurodegenerative diseases, osteoarthritis, tumors and metabolic syndrome, along with their ability to extend lifespan.SUMMARY: The purpose of aging research is the identification of interventions that may avoid or ameliorate the ravages of time. In other words, the quest is for healthy aging, where improved longevity is coupled to a corresponding healthspan extension. It is only by extending the healthy human lifespan that we will truly meet the premise of the Roman poet Cicero: “No one is so old as to think that he may not live a year.”KEYWORDS: aging, caloric restriction, mimetic, healthspan, sirtuin activator

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Analysis of the area and the number of pulmonary alveoli through the normal aging process in CD1 mouse

10.1101/2020.12.11.421032 ◽

2020 ◽

Author(s):

Marta Ortega-Martínez ◽

Esthefania Gutiérrez-Arenas ◽

Vanessa Gutiérrez-Dávila ◽

Alberto Niderhauser-García ◽

Ricardo M Cerda-Flores ◽

...

Keyword(s):

Aging Process ◽

Structural Changes ◽

Statistical Significance ◽

Age Groups ◽

Normal Aging ◽

P Values ◽

Pulmonary Alveoli ◽

Significant Difference ◽

Old Mice ◽

Alveolar Area

During the aging process, the lung exhibits structural changes accompanied by a decline in its function. The related information currently available is still scarce and contradictory. In addition, changes in some pulmonary parameters through aging process are species- and strain- dependent. The aim of this study was the assessment of the area and the number of pulmonary alveoli through the normal aging process in CD1 mouse. Paraffin-embedded sections of lungs from CD1 mice at age of 2, 6, 12, 18, or 24 months were stained with hematoxylin and eosin and examined using a light microscope. Images were captured using a camera linked to an image analysis software to measure areas and count alveoli. There was a significant difference in the alveolar area among the ages analyzed (F=87.53, Sig.=0.000). The alveolar area of the 6-, 12-, 18-, and 24-month-old mice was significantly greater (all p values < 0.001) than in mice at 2 months of age. Also, the alveolar number was significantly different among the ages tested (F=3.21, Sig.=0.023). The number of alveoli in mice at 2 months of age was greater than in mice at all other age groups, reaching statistical significance when compared with the 6-, 12-, and 18-month-old mice ( p values of 0.044, 0.014, and 0.002, respectively). Thus, we observed an increase in alveolar area and a decrease in alveolar number through the aging process. This information might be useful to understand pathologic changes underlying susceptibility of elderly individuals to chronic lower respiratory tract diseases.

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Identification and Analysis of Novel Biomarkers Involved in Chromophobe Renal Cell Carcinoma by Integrated Bioinformatics Analyses

BioMed Research International ◽

10.1155/2020/2671281 ◽

2020 ◽

Vol 2020 ◽

pp. 1-7

Author(s):

Wei Zhang ◽

Yin Xu ◽

Jinghan Zhang ◽

Jun Wu

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Molecular Mechanisms ◽

Clinical Manifestations ◽

Arachidonic Acid Metabolism ◽

Chromophobe Renal Cell Carcinoma ◽

Functional Enrichment ◽

Bioinformatics Analyses ◽

Novel Biomarkers

In renal cell carcinoma, chromophobe renal cell carcinoma (ChRCC) is a distinct subtype, whose clinical manifestations often lack specificity, and the molecular mechanisms of ChRCC tumorigenesis remain generally vague. The target of this study was to discover novel biomarkers involved in ChRCC by integrated bioinformatics analyses. We found 2608 differentially expressed genes (DEGs), of which 1518 were upregulated and 1090 were downregulated. Gene ontology (GO) analysis of DEGs uncovered significant functional enrichment in three aspects: biological process (BP), molecular function (MF), and cellular component (CC). The results of Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated DEGs were largely enriched in retinol metabolism, arachidonic acid metabolism, and pentose and glucuronate interconversions. Then, the protein–protein interactions (PPI) network was constructed and top three hub genes were identified by the Cytoscape plugin cytoHubba. Through calculating the degree, betweenness centrality, and Stress of mRNAs, CENPA was upregulated and KNG1 and AGT were downregulated. A survival assay performed according to Oncomine data showed only CENPA high expression exhibited a worse prognosis. This study identified crucial genes and pathways for the progress of ChRCC, and CENPA might be a novel biomarker for diagnosis, treatment, and prognosis of ChRCC.

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Extracellular Vesicles of GMSCs Alleviate Aging-Related Cell Senescence

Journal of Dental Research ◽

10.1177/0022034520962463 ◽

2020 ◽

pp. 002203452096246

Author(s):

H.Z. Shi ◽

J.C. Zeng ◽

S.H. Shi ◽

H. Giannakopoulos ◽

Q.Z. Zhang ◽

...

Keyword(s):

Oxidative Stress ◽

Endothelial Cells ◽

Extracellular Vesicles ◽

Cellular Senescence ◽

Healthy Aging ◽

Umbilical Vein ◽

Functional Decline ◽

Skin Fibroblasts ◽

Alternative Source ◽

Complex Biological Process

Healthy aging is a complex biological process with progressive accumulation of senescent cells characterized by stable cell cycle arrest, resulting in impaired homeostasis, regenerative potential, and gradual functional decline in multiple tissues and organs, whereby the aberrant activation of mammalian target of rapamycin (mTOR) signaling networks plays a central role. Herein, we explored the effects of extracellular vesicles (EVs) released by gingiva-derived mesenchymal stem cells (GMSC-EVs) on oxidative stress–induced cellular senescence in human endothelial cells and skin fibroblasts and their antiaging potentials. Our results showed that GMSC-EVs robustly abrogated oxidative stress–induced upregulation in the expression of cellular senescence-related genes, such as β-galactosidase, p21, p53, and γH2AX, and mTOR/pS6 signaling pathway, in human umbilical vein endothelial cells (HUVECs) and skin fibroblasts. Meanwhile, GMSC-EVs restored oxidative stress–induced impairment in proliferation and tube formation by HUVECs. Systemic administration of GMSC-EVs attenuated aging-associated elevation in the expression levels of p21, mTOR/pS6, interleukin 6, and tumor necrosis factor α in skin and heart tissues of aged mice. These findings suggest that GMSC-EVs could be a potential alternative source of cell-free product for attenuation of aging-related skin and vascular dysfunctions due to their potent inhibitory effects on oxidative stress–induced cellular senescence in endothelial cells and skin fibroblasts.

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Quantitative high resolution light and EM autoradiography of fluorophosphate-esterase in developing mouse liver

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s042482010008119x ◽

1978 ◽

Vol 36 (2) ◽

pp. 66-67

Author(s):

C. Budd

Keyword(s):

Electron Microscope ◽

High Resolution ◽

Mouse Liver ◽

Unit Area ◽

Irreversible Inhibitor ◽

Adult Mice ◽

Quantitative Measurements ◽

Em Autoradiography ◽

Old Mice ◽

Silver Grains

The distribution and concentration of fluorophosphate reactive (FPR) esterases in the liver of developing and adult mice was determined quantitatively from light and electron microscope autoradiograms of liver reacted with 3H - diisopropylfluorophosphate (3H-DFP) an irreversible inhibitor of carboxylesterases.The majority of labeled cells in the liver of 2, 8, 14 and 28- day-old mice and in adult mice (60-180 days old) were hepatocytes, but in the liver from 2-day-old mice and to a lesser extent 8-day-old mice, the autoradiographic silver grains were also concentrated over granulocytes of the intrahepatic hemopoietic population.Quantitative measurements of grain density (developed silver grains/unit area) in light microscope autoradiograms revealed an increase in the predominantly cytoplasmic concentration of FPR esterase sites in hepatocytes from 137o of the adult concentration in 2-day-old mice, to 497, and 78% of the adult concentration in 8- and 14-day-old animals, respectively.

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Inflammaging of Female Reproductive System: a Molecular Landscape

Current Aging Science ◽

10.2174/1874609813666200929112624 ◽

2020 ◽

Vol 13 ◽

Author(s):

Valeriia Rodichkina ◽

Igor Kvetnoy ◽

Victoria Polyakova ◽

Alexander Arutjunyan ◽

Ruslan Nasyrov ◽

...

Keyword(s):

Cellular Senescence ◽

Functional Decline ◽

Reproductive Function ◽

Reproductive Age ◽

Loss Of Function ◽

Negative Effects ◽

Age Related ◽

Complex Biological Process ◽

Secretory Phenotype ◽

Cellular Stresses

: Aging is a complex biological process, a major aspect of which is the accumulation of somatic changes throughout the life. Cellular senescence is a condition in which cells undergo an irreversible cell cycle arrest in response to various cellular stresses. Once the cells begin to senesce, they become more resistant to any mutagens, including oncogenic factors. Inflammaging (inflammatory aging) is an age-related, chronic and systemic inflammatory condition realized by cells with the senescence associated secretory phenotype (SASP). These recently recognized senescent phenotypes associated with aging have been reported to promote better wound healing, embryonic development, as well as stimulation and extension of the tumor process. It is assumed that cellular senescence contributes to age-related decline of reproductive function due to the association of senescent cells with aging and age-related diseases. Thus, SASPs have both positive and negative effects, depending on the biological context. SASP cell accumulation in tissues contributes to an age-related functional decline of the tissue and organ state. In this review, the term “cellular senescence” is used to refer the processes of cells irreversible growth inhibition during their viable state, while the term “aging” is used to indicate the deterioration of tissues due to loss of function. Late reproductive age is associated with infertility and possible complications of the onset and maintenance of pregnancy. Senescent cells express pro-inflammatory cytokines, growth factors, and matrix metalloproteinases and some other molecules, collectively called the senescence associated secretory phenotype (SASP).

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INTEREST GROUP SESSION—EPIDEMIOLOGY OF AGING: BIOSOCIAL RESEARCH ON BRAIN AGING AND BIOLOGICAL AGING

Innovation in Aging ◽

10.1093/geroni/igz038.1259 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

pp. S348-S348

Author(s):

Daniel W Belsky

Keyword(s):

Life Course ◽

Cognitive Aging ◽

Brain Aging ◽

Functional Decline ◽

Biological Aging ◽

Social Psychological ◽

Aging Research ◽

System Integrity ◽

Organ Systems ◽

The Brain

Abstract Our aging global population presents a new set of challenges for public health. Individual-disease focused models are becoming outmoded as geriatricians recognize multimorbidity and frailty as the central challenges in preserving health for older adults. Evidence from research into the biology of aging suggests that a set of common cellular-level processes underpin decline in system integrity that induces vulnerability to disease across multiple organ systems, including the brain. In parallel, research in life-course gerontology indicates that the roots of aging-related decline in system integrity extend from early life and encompass histories of social, psychological, and biochemical exposures. The research presented in this symposium aims to integrate these emerging paradigms in aging research by mapping connections among measures of aging in the brain and body and social, psychological, and nutrition exposures. Our symposium focuses on (1) links between social-psychological determinants of health and biological aging in the brain and body; and (2) social and behavioral protective factors that may buffer emerging biological risk in aging. The overarching goal of this symposium is to introduce an approach to gerontology that integrates geroscience with life-course social and psychiatric epidemiology to advance understanding of cognitive aging and functional decline, and ultimately identify novel interventions to extend healthy lifespan.

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