0000000000559830

AUTHOR

Steve Horvath

Genome-wide association studies identify 137 genetic loci for DNA methylation 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 ass…

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Additional file 4 of Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging

Additional file 4. Assessment of genomic inflation and heterogeneity.

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Additional file 3 of Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging

Additional file 3. Supplementary Figures - Figures S1-S31.

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Additional file 6 of Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging

Additional file 6. Review history.

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Small extracellular vesicles from young mice prevent frailty, improve healthspan and decrease epigenetic age in old mice

SummaryAging is associated with an increased risk of frailty, disability, comorbidities, institutionalization, falls, fractures, hospitalization, and mortality. Searching for strategies to delay the degenerative changes associated with aging and frailty is interesting. We treated old animals intravenously with small extracellular vesicles (sEVs) derived from adipose mesenchymal stem cells (ADSCs) of young animals, and we found an improvement of several functional parameters usually altered with aging, such as motor coordination, grip strength, fatigue resistance, fur regeneration, and renal function. Frailty index analysis showed that 40% of old control mice were frail, whereas none of the …

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Additional file 5 of Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging

Additional file 5. Colocalization plots.

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Additional file 1 of Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging

Additional file 1. Individual cohort descriptions and acknowledgements.

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Additional file 5 of Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging

Additional file 5. Colocalization plots.

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Additional file 6 of Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging

Additional file 6. Review history.

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Genome-wide association studies identify 137 loci for DNA methylation biomarkers of ageing

AbstractBiological ageing estimators derived from DNA methylation (DNAm) data are heritable and correlate with morbidity and mortality. Leveraging DNAm and SNP data from >41,000 individuals, we identify 137 genome-wide significant loci (113 novel) from meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We report strong genetic correlations with longevity and lifestyle factors such as smoking, education, and obesity. Significant associations are observed in polygenic risk score analysis and to a lesser extent in Mendelian randomization analyses. This study illuminates the genetic …

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Small extracellular vesicles from young adipose-derived stem cells prevent frailty, improve health span, and decrease epigenetic age in old mice.

Aging is associated with an increased risk of frailty, disability, and mortality. Strategies to delay the degenerative changes associated with aging and frailty are particularly interesting. We treated old animals with small extracellular vesicles (sEVs) derived from adipose mesenchymal stem cells (ADSCs) of young animals, and we found an improvement in several parameters usually altered with aging, such as motor coordination, grip strength, fatigue resistance, fur regeneration, and renal function, as well as an important decrease in frailty. ADSC-sEVs induced proregenerative effects and a decrease in oxidative stress, inflammation, and senescence markers in muscle and kidney. Moreover, pre…

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Additional file 2 of Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging

Additional file 2. Supplementary Tables -Tables S1-S31.

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Additional file 2 of Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging

Additional file 2. Supplementary Tables -Tables S1-S31.

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