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UMass Metabolic Network Publications

Biochemistry

Aging

Articles 1 - 3 of 3

Full-Text Articles in Molecular Biology

Mitochondrial Stress Restores The Heat Shock Response And Prevents Proteostasis Collapse During Aging, Johnathan Labbadia, Renee M. Brielmann, Mario F. Neto, Yi-Fan Lin, Cole M. Haynes, Richard I. Morimoto Nov 2017

Mitochondrial Stress Restores The Heat Shock Response And Prevents Proteostasis Collapse During Aging, Johnathan Labbadia, Renee M. Brielmann, Mario F. Neto, Yi-Fan Lin, Cole M. Haynes, Richard I. Morimoto

UMass Metabolic Network Publications

In Caenorhabditis elegans, the programmed repression of the heat shock response (HSR) accompanies the transition to reproductive maturity, leaving cells vulnerable to environmental stress and protein aggregation with age. To identify the factors driving this event, we performed an unbiased genetic screen for suppressors of stress resistance and identified the mitochondrial electron transport chain (ETC) as a central regulator of the age-related decline of the HSR and cytosolic proteostasis. Mild downregulation of ETC activity, either by genetic modulation or exposure to mitochondria-targeted xenobiotics, maintained the HSR in adulthood by increasing HSF-1 binding and RNA polymerase II recruitment at HSF-1 target ...


Age-Associated Microrna Expression In Human Peripheral Blood Is Associated With All-Cause Mortality And Age-Related Traits, Tianxiao Huan, George Chen, Chunyu Liu, Anindya Bhattacharya, Jian Rong, Brian H. Chen, Sudha Seshadri, Kahraman Tanriverdi, Jane E. Freedman, Martin G. Larson, Joanne M. Murabito, Daniel Levy Oct 2017

Age-Associated Microrna Expression In Human Peripheral Blood Is Associated With All-Cause Mortality And Age-Related Traits, Tianxiao Huan, George Chen, Chunyu Liu, Anindya Bhattacharya, Jian Rong, Brian H. Chen, Sudha Seshadri, Kahraman Tanriverdi, Jane E. Freedman, Martin G. Larson, Joanne M. Murabito, Daniel Levy

UMass Metabolic Network Publications

Recent studies provide evidence of correlations of DNA methylation and expression of protein-coding genes with human aging. The relations of microRNA expression with age and age-related clinical outcomes have not been characterized thoroughly. We explored associations of age with whole-blood microRNA expression in 5221 adults and identified 127 microRNAs that were differentially expressed by age at P < 3.3 x 10(-4) (Bonferroni-corrected). Most microRNAs were underexpressed in older individuals. Integrative analysis of microRNA and mRNA expression revealed changes in age-associated mRNA expression possibly driven by age-associated microRNAs in pathways that involve RNA processing, translation, and immune function. We fitted a linear model to predict 'microRNA age' that incorporated expression levels of 80 microRNAs. MicroRNA age correlated modestly with predicted age from DNA methylation (r = 0.3) and mRNA expression (r = 0.2), suggesting that microRNA age may complement mRNA and epigenetic age prediction models. We used the difference between microRNA age and chronological age as a biomarker of accelerated aging (Deltaage) and found that Deltaage was associated with all-cause mortality (hazards ratio 1.1 per year difference, P = 4.2 x 10(-5) adjusted for sex and chronological age). Additionally, Deltaage was associated with coronary heart disease, hypertension, blood pressure, and glucose levels. In conclusion, we constructed a microRNA age prediction model based on whole-blood microRNA expression profiling. Age-associated microRNAs and their targets have potential utility to detect accelerated aging and to predict risks for age-related diseases. Wiley and Sons Ltd.


Cross-Sectional Relations Of Whole-Blood Mirna Expression Levels And Hand Grip Strength In A Community Sample, Joanne M. Murabito, Jian Rong, Kathryn L. Lunetta, Tianxiao Huan, Honghuang Lin, Qiang Zhao, Jane E. Freedman, Kahraman Tanriverdi, Daniel Levy, Martin G. Larson Aug 2017

Cross-Sectional Relations Of Whole-Blood Mirna Expression Levels And Hand Grip Strength In A Community Sample, Joanne M. Murabito, Jian Rong, Kathryn L. Lunetta, Tianxiao Huan, Honghuang Lin, Qiang Zhao, Jane E. Freedman, Kahraman Tanriverdi, Daniel Levy, Martin G. Larson

UMass Metabolic Network Publications

MicroRNAs (miRNAs) regulate gene expression with emerging data suggesting miRNAs play a role in skeletal muscle biology. We sought to examine the association of miRNAs with grip strength in a community-based sample. Framingham Heart Study Offspring and Generation 3 participants (n = 5668 54% women, mean age 55 years, range 24, 90 years) underwent grip strength measurement and miRNA profiling using whole blood from fasting morning samples. Linear mixed-effects regression modeling of grip strength (kg) versus continuous miRNA 'Cq' values and versus binary miRNA expression was performed. We conducted an integrative miRNA-mRNA coexpression analysis and examined the enrichment of biologic pathways ...