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Browsing by Author "Niculescu, Alexander B., III"
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Item Convergence of recent GWAS data for suicidality with previous blood biomarkers: independent reproducibility using independent methodologies in independent cohorts(Nature, 2020) Niculescu, Alexander B., III; Le-Niculescu, Helen; Psychiatry, School of MedicineRecent genetic studies for suicidality, including four independent GWAS, have not reproduced each other’s top implicated genes. While arguments of heterogeneity, methodology, and sample sizes can be invoked, heterogeneity is a feature, not a “bug” (as is well understood in biology and in personalized medicine). A comprehensive body of work on blood biomarkers for suicidality has previously been published by our group. We examine the issue of reproducibility using these different approaches, and provide reassuring evidence for convergence of findings, as well as some generalizable insights.Item Suppression of transcriptional drift extends C. elegans lifespan by postponing the onset of mortality(2015-12) Rangaraju, Sunitha; Solis, Gregory M.; Thompson, Ryan C.; Gomez-Amaro, Rafael L.; Kurian, Leo; Encalada, Sandra E.; Niculescu, Alexander B., III; Salomon, Daniel R.; Petrascheck, Michael; Department of Psychiatry, IU School of MedicineLongevity mechanisms increase lifespan by counteracting the effects of aging. However, whether longevity mechanisms counteract the effects of aging continually throughout life, or whether they act during specific periods of life, preventing changes that precede mortality is unclear. Here, we uncover transcriptional drift, a phenomenon that describes how aging causes genes within functional groups to change expression in opposing directions. These changes cause a transcriptome-wide loss in mRNA stoichiometry and loss of co-expression patterns in aging animals, as compared to young adults. Using Caenorhabditis elegans as a model, we show that extending lifespan by inhibiting serotonergic signals by the antidepressant mianserin attenuates transcriptional drift, allowing the preservation of a younger transcriptome into an older age. Our data are consistent with a model in which inhibition of serotonergic signals slows age-dependent physiological decline and the associated rise in mortality levels exclusively in young adults, thereby postponing the onset of major mortality.