scholarly journals Genome-wide identification of functional tRNA-derived fragments in Senescence-accelerated mouse prone 8 brain

2018 ◽  
Author(s):  
Shuai Zhang ◽  
Hejian Li ◽  
Ling Zheng ◽  
Hong Li ◽  
Chengqiang Feng ◽  
...  
Keyword(s):  
Parkinson Disease ◽  
Target Genes ◽  
Brain Aging ◽  
State Of The Art ◽  
Regulation Of Gene Expression ◽  
Age Related ◽  
Genome Wide ◽  
Age Dependent ◽  
Samp8 Mice ◽  
Senescence Accelerated Mouse

AbstracttRNA-derived fragments (tRFs) have been linked previously to the development of various diseases, such as cancer and viral infection. However, tRFs seem also related to brain aging and related diseases, especially Alzheimer and Parkinson disease. RNA sequencing, a state-of-the-art technology, has allowed for investigation of tRFs in this field. In this study, we investigated the changes of tRFs in the brains of a senescence-accelerated mouse model, senescence-accelerated mouse prone 8 (SAMP8), that show age-dependent deficits in learning and memory; and a control model, senescence-accelerated mouse resistant 1 (SAMR1), with normal aging, both at 7 months of age. A total of 570 tRF transcripts were discovered. Among these transcripts, 8, including 3 upregulated and 5 downregulated transcripts, were differentially expressed in the SAMP8 mice. Then, we obtained 110 potential target genes in a miRNA-like pattern. GO survey implicated these target genes in the function of various aspects, e.g. postsynaptic density (GO: 0014069). Furthermore, we assessed in detail those tRFs whose miRNA-like pattern was most likely to affect the progression of either Alzheimer and Parkinson disease, such as AS-tDR-011775 acting onMobpandPark2. In fact, we found the tRFs to be involved in the regulation of gene expression by means other than the miRNA-like pattern. Therefore, these 8 dysregulated tRFs may hold consequences far into the future and can be attractive biomarkers and valid targets. In brief, our study is the first to provide a comprehensive analysis on tRFs in SAMP8 mouse brain, and this breakthrough identified promising new targets for preventing the age-related changes of brain and the therapeutic intervention of Alzheimer’s and Parkinson’s.

scholarly journals Erinacine A-Enriched Hericium erinaceus Mycelium Delays Progression of Age-Related Cognitive Decline in Senescence Accelerated Mouse Prone 8 (SAMP8) Mice

Nutrients ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 3659
Author(s):  
Li-Ya Lee ◽  
Wayne Chou ◽  
Wan-Ping Chen ◽  
Ming-Fu Wang ◽  
Ying-Ju Chen ◽  
...  
Keyword(s):  
Learning And Memory ◽  
Active Avoidance ◽  
Brain Aging ◽  
Cognitive Disability ◽  
Neuroprotective Effects ◽  
Hericium Erinaceus ◽  
Age Related ◽  
Erinacine A ◽  
Samp8 Mice ◽  
Senescence Accelerated Mouse

There have been many reports on the neuroprotective effects of Hericium erinaceus mycelium, in which the most well-known active compounds found are diterpenoids, such as erinacine A. Previously, erinacine A-enriched Hericeum erinaceus mycelium (EAHEM) was shown to decrease amyloid plaque aggregation and improve cognitive disability in Alzheimer’s disease model APP/PS1 mice. However, its effects on brain aging have not yet been touched upon. Here, we used senescence accelerated mouse prone 8 (SAMP8) mice as a model to elucidate the mechanism by which EAHEM delays the aging of the brain. Three-month-old SAMP8 mice were divided into three EAHEM dosage groups, administered at 108, 215 and 431 mg/kg/BW/day, respectively. During the 12th week of EAHEM feeding, learning and memory of the mice were evaluated by single-trial passive avoidance and active avoidance test. After sacrifice, the amyloid plaques, induced nitric oxidase synthase (iNOS) activity, thiobarbituric acid-reactive substances (TBARS) and 8-OHdG levels were analyzed. We found that the lowest dose of 108 mg/kg/BW EAHEM was sufficient to significantly improve learning and memory in the passive and active avoidance tests. In all three EAHEM dose groups, iNOS, TBARS and 8-OHdG levels all decreased significantly and showed a dose-dependent response. The results indicate that EAHEM improved learning and memory and delayed degenerative aging in mice brains.

scholarly journals Genome-wide H3K9 Acetylation Level Increases with Age-Dependent Senescence of Flag Leaf in Rice (Oryza sativa)

2021 ◽  
Author(s):  
Yu Zhang ◽  
Yanyun Li ◽  
Yuanyuan Zhang ◽  
Zeyu Zhang ◽  
Deyu Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Oryza Sativa ◽  
Leaf Senescence ◽  
Epigenetic Modification ◽  
Flag Leaf ◽  
Regulation Of Gene Expression ◽  
Leaf Aging ◽  
Genome Wide ◽  
Age Dependent ◽  
H3k9 Acetylation

Flag leaf senescence is an important biological process that drives the remobilization of nutrients to the growing organs of rice. Leaf senescence is controlled by genetic information via gene expression and epigenetic modification, but the precise mechanism is as of yet unclear. Here, we analyzed genome-wide acetylated lysine residue 9 of histone H3 (H3K9ac) enrichment by chromatin immunoprecipitation-sequencing (ChIP-seq) and examined its association with transcriptomes by RNA-seq during flag leaf aging in rice (Oryza sativa). We found that genome-wide H3K9 acetylation levels increased with age-dependent senescence in rice flag leaf, and there was a positive correlation between the density and breadth of H3K9ac and gene expression and transcript elongation. A set of 1,249 up-regulated, differentially expressed genes (DEGs) and 996 down-regulated DEGs showing a strong relationship between temporal changes in gene expression and gain/loss of H3K9ac was observed during rice flag leaf aging. We produced a landscape of H3K9 acetylation- modified gene expression targets that includes known senescence-associated genes, metabolism-related genes, as well as miRNA biosynthesis- related genes. Our findings reveal a complex regulatory network of metabolism- and senescence-related pathways mediated by H3K9ac and also elucidate patterns of H3K9ac-mediated regulation of gene expression during flag leaf aging in rice.

scholarly journals 3,4-Dihydroxybenzalacetone (DBL) Prevents Aging-Induced Myocardial Changes in Senescence-Accelerated Mouse-Prone 8 (SAMP8) Mice

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 597
Author(s):  
Vijayasree V. Giridharan ◽  
Vengadeshprabhu Karupppagounder ◽  
Somasundaram Arumugam ◽  
Yutaka Nakamura ◽  
Ashrith Guha ◽  
...  
Keyword(s):  
Dna Damage ◽  
Oxidative Dna Damage ◽  
Cardiac Fibrosis ◽  
Myocardial Dysfunction ◽  
The Elderly ◽  
Tunel Staining ◽  
Inonotus Obliquus ◽  
Age Related ◽  
Samp8 Mice ◽  
Senescence Accelerated Mouse

Aging is a predominant risk factor for the development and progression of cardiovascular complications. Physiologically and anatomically, the heart undergoes numerous changes that result in poor cardiac function in the elderly population. Recently, several studies have provided promising results, confirming the ability of the senescence-accelerated mouse-prone 8 (SAMP8) model to accurately model age-related cardiovascular alterations. In this study, using a murine model of senescence, SAMP8, we aimed to investigate the effect of 3,4-dihydroxybenzalacetone (DBL), a catechol-containing phenylpropanoid derivative isolated from Inonotus obliquus (Chaga), on cardiac aging. DBL was administered at the doses of 10 mg/kg and 20 mg/kg by oral gavage to SAMP8 mice to examine aging-mediated cardiac changes, such as oxidative DNA damage, oxygen radical antioxidant capacity (ORAC) value, fibrosis, inflammation, and apoptosis. The treatment with DBL at both doses significantly reduced aging-mediated oxidative DNA damage, and simultaneously increased the ORAC value in the SAMP8 assay. Cardiac fibrosis was assessed with Azan-Mallory staining, and the number of cardiac remodeling markers was found to be significantly reduced after the treatment with DBL. We also observed a decrease in cardiomyocyte apoptosis as measured by the terminal transferase-mediated dUTP nick end labeling (TUNEL) staining method and the caspase-3 levels in SAMP8 mice compared with senescence-resistant control (SAMR1) mice. The findings from this study suggest that DBL has a potentially beneficial effect on aging-mediated myocardial alterations. Further studies are warranted to confirm the promising potential of this catechol compound against aging-associated myocardial dysfunction.

scholarly journals Family-based exome sequencing identifies rare coding variants in age-related macular degeneration

2020 ◽  
Vol 29 (12) ◽  
pp. 2022-2034 ◽  
Author(s):  
Rinki Ratnapriya ◽  
İlhan E Acar ◽  
Maartje J Geerlings ◽  
Kari Branham ◽  
Alan Kwong ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Exome Sequencing ◽  
Target Genes ◽  
Rare Variants ◽  
Age Related Macular Degeneration ◽  
Genome Wide Association Studies ◽  
Age Related ◽  
Genome Wide ◽  
Candidate Target ◽  
Coding Variants

Abstract Genome-wide association studies (GWAS) have identified 52 independent variants at 34 genetic loci that are associated with age-related macular degeneration (AMD), the most common cause of incurable vision loss in the elderly worldwide. However, causal genes at the majority of these loci remain unknown. In this study, we performed whole exome sequencing of 264 individuals from 63 multiplex families with AMD and analyzed the data for rare protein-altering variants in candidate target genes at AMD-associated loci. Rare coding variants were identified in the CFH, PUS7, RXFP2, PHF12 and TACC2 genes in three or more families. In addition, we detected rare coding variants in the C9, SPEF2 and BCAR1 genes, which were previously suggested as likely causative genes at respective AMD susceptibility loci. Identification of rare variants in the CFH and C9 genes in our study validated previous reports of rare variants in complement pathway genes in AMD. We then extended our exome-wide analysis and identified rare protein-altering variants in 13 genes outside the AMD-GWAS loci in three or more families. Two of these genes, SCN10A and KIR2DL4, are of interest because variants in these genes also showed association with AMD in case-control cohorts, albeit not at the level of genome-wide significance. Our study presents the first large-scale, exome-wide analysis of rare variants in AMD. Further independent replications and molecular investigation of candidate target genes, reported here, would assist in gaining novel insights into mechanisms underlying AMD pathogenesis.

scholarly journals Lactobacillus paracasei PS23 Delays Progression of Age-Related Cognitive Decline in Senescence Accelerated Mouse Prone 8 (SAMP8) Mice

Nutrients ◽  
2018 ◽  
Vol 10 (7) ◽  
pp. 894 ◽  
Author(s):  
Shih-Yi Huang ◽  
Li-Han Chen ◽  
Ming-Fu Wang ◽  
Chih-Chieh Hsu ◽  
Ching-Hung Chan ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Brain Dysfunction ◽  
Lactobacillus Paracasei ◽  
Oxidative Enzymes ◽  
Control Group ◽  
Age Related ◽  
Chemotactic Protein ◽  
Age Related Cognitive Decline ◽  
Samp8 Mice ◽  
Senescence Accelerated Mouse

Probiotic supplements are potential therapeutic agents for age-related disorders due to their antioxidant and anti-inflammatory properties. However, the effect of probiotics on age-related brain dysfunction remains unclear. To investigate the effects of Lactobacillus paracasei PS23 (LPPS23) on the progression of age-related cognitive decline, male and female senescence-accelerated mouse prone 8 (SAMP8) mice were divided into two groups (n = 6 each): the control and PS23 groups. From the age of 16 weeks, these groups were given saline and LPPS23, respectively, because SAMP8 mice start aging rapidly after four months of age. After 12 weeks of treatment, we evaluated the effect of LPPS23 by analyzing their appearance, behavior, neural monoamines, anti-oxidative enzymes, and inflammatory cytokines. The PS23 group showed lower scores of senescence and less serious anxiety-like behaviors and memory impairment compared to the control group. The control mice also showed lower levels of neural monoamines in the striatum, hippocampus, and serum. Moreover, LPPS23 induced the anti-oxidative enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx). Higher levels of tumor necrosis factor (TNF)-α and monocyte chemotactic protein-1 (MCP1) and lower levels of interleukin (IL)-10 indicated that LPPS23 modulated the inflammation. Our results suggest that LPPS23 supplements could delay age-related cognitive decline, possibly by preventing oxidation and inflammation and modulating gut–brain axis communication.

Age-related changes in the oestrous cycle and reproductive hormones in senescence-accelerated mouse

2005 ◽  
Vol 17 (5) ◽  
pp. 507 ◽  
Author(s):  
Ma Yuan ◽  
Zhou Wen-Xia ◽  
Cheng Jun-Ping ◽  
Zhang Yong-Xiang
Keyword(s):  
Substance P ◽  
Luteinising Hormone ◽  
Reproductive Hormones ◽  
Oestrous Cycle ◽  
Reproductive Hormone ◽  
Hormone Levels ◽  
Age Related ◽  
Samp8 Mice ◽  
Senescence Accelerated Mouse ◽  
Age Related Changes

To investigate age-related changes in the oestrous cycle and reproductive hormone levels in senescence-accelerated mouse (SAM), we examined these parameters in 3-, 5-, 7-, 9- and 11-month-old female SAM-prone/8 (SAMP8) and SAM-resistant/1 (SAMR1) strains. Levels of β-endorphin (β-EP) and substance P (SP) in the hypothalamus were also measured. The oestrous cycle and dioestrus of 9-month-old SAMP8 mice were significantly prolonged compared with age-matched SAMR1 mice. Furthermore, the concentration of serum oestradiol was lower and the level of pituitary luteinising hormone was higher in SAMP8 mice compared with SAMR1 mice. This characterises the hypothalamus–pituitary–ovary (HPO) axis of the SAMP8 strain as hypergonadotropic–hypogonad. The levels of β-EP and SP in the SAMP8 hypothalamus were lower than in the SAMR1 hypothalamus. These results indicate that the function of the HPO axis in SAMP8 mice declines early and this may be attributed, in part, to the decline in β-EP and SP concentrations in the hypothalamus.

Erratum to: Age-related changes in the oestrous cycle and reproductive hormones in senescence-accelerated mouse

2009 ◽  
Vol 21 (4) ◽  
pp. 624
Author(s):  
Ma Yuan ◽  
Zhou Wen-Xia ◽  
Cheng Jun-Ping ◽  
Zhang Yong-Xiang
Keyword(s):  
Substance P ◽  
Luteinising Hormone ◽  
Reproductive Hormones ◽  
Oestrous Cycle ◽  
Reproductive Hormone ◽  
Hormone Levels ◽  
Age Related ◽  
Samp8 Mice ◽  
Senescence Accelerated Mouse ◽  
Age Related Changes

To investigate age-related changes in the oestrous cycle and reproductive hormone levels in senescence-accelerated mouse (SAM), we examined these parameters in 3-, 5-, 7-, 9- and 11-month-old female SAM-prone/8 (SAMP8) and SAM-resistant/1 (SAMR1) strains. Levels of �-endorphin (�-EP) and substance P (SP) in the hypothalamus were also measured. The oestrous cycle and dioestrus of 9-month-old SAMP8 mice were significantly prolonged compared with age-matched SAMR1 mice. Furthermore, the concentration of serum oestradiol was lower and the level of pituitary luteinising hormone was higher in SAMP8 mice compared with SAMR1 mice. This characterises the hypothalamus.pituitary.ovary (HPO) axis of the SAMP8 strain as hypergonadotropic.hypogonad. The levels of �-EP and SP in the SAMP8 hypothalamus were lower than in the SAMR1 hypothalamus. These results indicate that the function of the HPO axis in SAMP8 mice declines early and this may be attributed, in part, to the decline in �-EP and SP concentrations in the hypothalamus.

Age-related autophagy alterations in the brain of senescence accelerated mouse prone 8 (SAMP8) mice

2011 ◽  
Vol 46 (7) ◽  
pp. 533-541 ◽  
Author(s):  
Qinying Ma ◽  
Jing Qiang ◽  
Ping Gu ◽  
Yanyong Wang ◽  
Yuan Geng ◽  
...  
Keyword(s):  
Age Related ◽  
Samp8 Mice ◽  
The Brain ◽  
Senescence Accelerated Mouse

scholarly journals Long Non-coding RNA Signatures Associated With Liver Aging in Senescence-Accelerated Mouse Prone 8 Model

2021 ◽  
Vol 9 ◽  
Author(s):  
Shuai Zhang ◽  
Juanjuan Duan ◽  
Yu Du ◽  
Jinlu Xie ◽  
Haijing Zhang ◽  
...  
Keyword(s):  
Mouse Liver ◽  
Systematic Research ◽  
Physiological Processes ◽  
Age Related ◽  
Non Coding Rna ◽  
Genome Wide ◽  
Potential Link ◽  
Non Coding Rnas ◽  
Long Non Coding Rna ◽  
Senescence Accelerated Mouse

The liver is sensitive to aging because the risk of hepatopathy, including fatty liver, hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma, increases dramatically with age. Long non-coding RNAs (lncRNAs) are >200 nucleotides long and affect many pathological and physiological processes. A potential link was recently discovered between lncRNAs and liver aging; however, comprehensive and systematic research on this topic is still limited. In this study, the mouse liver genome-wide lncRNA profiles of 8-month-old SAMP8 and SAMR1 models were explored through deep RNA sequencing. A total of 605,801,688 clean reads were generated. Among the 2,182 identified lncRNAs, 28 were differentially expressed between SAMP8 and SAMR1 mice. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) surveys showed that these substantially dysregulated lncRNAs participated in liver aging from different aspects, such as lipid catabolic (GO: 0016042) and metabolic pathways. Further assessment was conducted on lncRNAs that are most likely to be involved in liver aging and related diseases, such as LNC_000027, LNC_000204E, NSMUST00000144661.1, and ENSMUST00000181906.1 acted on Ces1g. This study provided the first comprehensive dissection of lncRNA landscape in SAMP8 mouse liver. These lncRNAs could be exploited as potential targets for the molecular-based diagnosis and therapy of age-related liver diseases.

scholarly journals Impaired dynamics of brain precapillary sphincters and first order capillaries explains reduced neurovascular functions in aging

2021 ◽  
Author(s):  
Changsi Cai ◽  
Stefan Andreas Zambach ◽  
Soeren Grubb ◽  
Kirsten Joan Thomsen ◽  
Barbara Lykke Lind ◽  
...  
Keyword(s):  
Blood Flow ◽  
Vascular Reactivity ◽  
Brain Aging ◽  
Capillary Density ◽  
Nitric Oxide Synthase Inhibitor ◽  
First Order ◽  
Age Related ◽  
Age Dependent ◽  
Synthase Inhibitor

The microvascular inflow tract (MIT), i.e. penetrating arterioles, precapillary sphincters and first order capillaries, is the bottleneck for brain blood flow and energy supply. However, the exact structural and functional alterations during aging remain elusive. Using in vivo 4-dimensional (xyzt) two-photon imaging, we showed an age-dependent decrease in vaso-responsivity, which was accompanied by reduced sensitivity of MIT to pinacidil and papaverine, and to vasoconstrictors endothelin-1 and to L-NAME, a nitric oxide synthase inhibitor. Reduced responsivity was accompanied by an age-dependent decrease in capillary density close to the arterioles and by loss of pericyte processes, whereas the number of pericyte somas and the pericyte αSMA density were preserved. The age-related reduction in vascular reactivity was most pronounced at precapillary sphincters, highlighting its crucial role for capillary blood flow regulation. Mathematical modeling further revealed dysregulated but protected pressure and flow in aged mice towards vasoconstriction. Prevention of reduced responsivity of the MIT may ameliorate the blood flow decrease associated with brain aging and age-related brain frailty.

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