Epigenomic, Transcriptome and Image-Based Biomarkers of Aging

Abstract Background Biological aging estimators derived from DNA methylation data are heritable and correlate with morbidity and mortality. Consequently, identification of genetic and environmental contributors to the variation in these measures in populations has become a major goal in the field. Results Leveraging DNA methylation and SNP data from more than 40,000 individuals, we identify 137 genome-wide significant loci, of which 113 are novel, from genome-wide association study (GWAS) meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We find evidence for shared genetic loci associated with the Horvath clock and expression of transcripts encoding genes linked to lipid metabolism and immune function. Notably, these loci are independent of those reported to regulate DNA methylation levels at constituent clock CpGs. A polygenic score for GrimAge acceleration showed strong associations with adiposity-related traits, educational attainment, parental longevity, and C-reactive protein levels. Conclusion This study illuminates the genetic architecture underlying epigenetic aging and its shared genetic contributions with lifestyle factors and longevity.

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Financial Resources and Biomarkers of Aging in the National Health and Aging Trends Study

Innovation in Aging ◽

10.1093/geroni/igaa057.1974 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

pp. 589-589

Author(s):

Laura Samuel ◽

Laken Roberts ◽

Danielle Boyce ◽

Melissa Hladek ◽

Sarah LaFave ◽

...

Keyword(s):

Hemoglobin A1c ◽

Income Group ◽

Cross Sectional Study ◽

Financial Strain ◽

Diabetes Diagnosis ◽

Lower Income ◽

Sampling Weights ◽

Cross Sectional ◽

Lower Income Group ◽

Biomarkers Of Aging

Abstract Lower income and financial strain (i.e. difficulty making ends meet) are associated with worse aging biomarkers, but evidence among nationally representative samples is limited. This cross-sectional study tested whether income to poverty ratio (analyzed separately for those <500% vs. ≥500% poverty threshold) and financial strain are associated with biomarkers of aging among NHATS participants aged ≥65 years (n=4,648), adjusting for age, race/ethnicity, gender, smoking, BMI, and diabetes diagnosis for hemoglobin A1c. Sampling weights were applied. Among those with incomes <500% poverty, higher income was associated with lower hemoglobin A1c (b= -0.0196, p=0.007), CMV (b= -0.0689, p<0.001) and CRP (b= -0.0428, p=0.012). Among those with incomes ≥500%, higher income was associated with lower IL-6 (b= -0.0001, p=0.023) and lower CMV (b= -0.0001, p<0.001). Financial strain was not associated with biomarkers. Income is more strongly associated with biomarkers among the lower income group, calling for special attention to this vulnerable population.

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Influence of Dopamine on Fluorescent Advanced Glycation End Products Formation Using Drosophila melanogaster

Biomolecules ◽

10.3390/biom11030453 ◽

2021 ◽

Vol 11 (3) ◽

pp. 453

Author(s):

Ana Filošević Vujnović ◽

Katarina Jović ◽

Emanuel Pištan ◽

Rozi Andretić Waldowski

Keyword(s):

Drosophila Melanogaster ◽

Advanced Glycation End Products ◽

Model Organism ◽

Covalent Modification ◽

Advanced Glycation ◽

Biomarkers Of Aging ◽

Glycation End Products ◽

End Products

Non-enzymatic glycation and covalent modification of proteins leads to Advanced Glycation End products (AGEs). AGEs are biomarkers of aging and neurodegenerative disease, and can be induced by impaired neuronal signaling. The objective of this study was to investigate if manipulation of dopamine (DA) in vitro using the model protein, bovine serum albumin (BSA), and in vivo using the model organism Drosophila melanogaster, influences fluorescent AGEs (fAGEs) formation as an indicator of dopamine-induced oxidation events. DA inhibited fAGEs-BSA synthesis in vitro, suggesting an anti-oxidative effect, which was not observed when flies were fed DA. Feeding flies cocaine and methamphetamine led to increased fAGEs formation. Mutants lacking the dopaminergic transporter or the D1-type showed further elevation of fAGEs accumulation, indicating that the long-term perturbation in DA function leads to higher production of fAGEs. To confirm that DA has oxidative properties in vivo, we fed flies antioxidant quercetin (QUE) together with methamphetamine. QUE significantly decreased methamphetamine-induced fAGEs formation suggesting that the perturbation of DA function in vivo leads to increased oxidation. These findings present arguments for the use of fAGEs as a biomarker of DA-associated neurodegenerative changes and for assessment of antioxidant interventions such as QUE treatment.

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Biomarkers of Aging with Prognostic and Predictive Value in Non-Oncological Diseases

Current Medicinal Chemistry ◽

10.2174/092986709789057644 ◽

2009 ◽

Vol 16 (27) ◽

pp. 3469-3475 ◽

Cited By ~ 6

Author(s):

Christian Koppelstaetter ◽

Georg Kern ◽

Gert Mayer

Keyword(s):

Predictive Value ◽

Biomarkers Of Aging ◽

Oncological Diseases

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Identifying molecular targets for reverse aging using integrated network analysis of transcriptomic and epigenomic changes during aging

Scientific Reports ◽

10.1038/s41598-021-91811-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Hwang-Yeol Lee ◽

Yeonsu Jeon ◽

Yeon Kyung Kim ◽

Jae Young Jang ◽

Yun Sung Cho ◽

...

Keyword(s):

Network Model ◽

Expression Profiles ◽

Flow Analysis ◽

Gene Expression Profiles ◽

Molecular Targets ◽

Regulatory Mechanisms ◽

Integrated Network ◽

Signal Flow ◽

Biomarkers Of Aging ◽

Candidate Target

AbstractAging is associated with widespread physiological changes, including skeletal muscle weakening, neuron system degeneration, hair loss, and skin wrinkling. Previous studies have identified numerous molecular biomarkers involved in these changes, but their regulatory mechanisms and functional repercussions remain elusive. In this study, we conducted next-generation sequencing of DNA methylation and RNA sequencing of blood samples from 51 healthy adults between 20 and 74 years of age and identified aging-related epigenetic and transcriptomic biomarkers. We also identified candidate molecular targets that can reversely regulate the transcriptomic biomarkers of aging by reconstructing a gene regulatory network model and performing signal flow analysis. For validation, we screened public experimental data including gene expression profiles in response to thousands of chemical perturbagens. Despite insufficient data on the binding targets of perturbagens and their modes of action, curcumin, which reversely regulated the biomarkers in the experimental dataset, was found to bind and inhibit JUN, which was identified as a candidate target via signal flow analysis. Collectively, our results demonstrate the utility of a network model for integrative analysis of omics data, which can help elucidate inter-omics regulatory mechanisms and develop therapeutic strategies against aging.

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