Transcriptomic and epigenetic acceleration of neuronal maturation and aging

One of the major obstacles to using human stem cells in the laboratory is that even the best protocols yield immature or inconsistent cells. Geschwind and Horvath are using mathematical predictions to identify factors that drive neuronal maturation in the human brain but that are absent in neurons grown from stem cells in cell culture. They will use these factors to create more stable cultures that are more similar to functioning neurons in the brain. They have also identified an aging clock based on genetic measurements from thousands of cells and tissues, and will use similar methods to mimic the effects of aging in the laboratory.

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Affiliated Investigators

Daniel Geschwind, Ph.D.

University of California, Los Angeles

Dr. Daniel Geschwind is the Gordon and Virginia MacDonald Distinguished Professor of neurology, psychiatry and human genetics at the UCLA School of Medicine. He is director of the Neurogenetics Program and the Center for Autism Research and Treatment (CART) and co-director of the Center for Neurobehavioral Genetics in the Semel Institute at UCLA. His laboratory aims to develop a mechanistic understanding of neuropsychiatric diseases both via human genetic studies and in vivo and in vitro model systems, such as neural progenitors. The lab’s approach relies heavily on computational and bioinformatic methods, including gene network analysis in addition to wet laboratory experimentation. He received the Derek Denny-Brown Neurological Scholar Award from the American Neurological Association in 2004, the Scientific Service Award from Autism Speaks in 2007, the Ruane Prize for Child and Adolescent Psychiatric Research from the Brain and Behavior foundation in 2012 and is an elected member of the Institute of Medicine of the National Academies.

Steve Horvath, Ph.D.

University of California, Los Angeles

Dr. Steve Horvath is a Professor in the Departments of Human Genetics and Biostatistics at the University of California, Los Angeles. His research lies at the intersection of computational biology, genetics, epidemiology, and systems biology. He works on all aspects of biomarker development with a particular focus on genomic biomarkers of aging. He recently published an article that describes a highly accurate biomarker of aging known as epigenetic clock. Salient features of the epigenetic clock include its high accuracy and its applicability to a broad spectrum of tissues and cell types. Dr. Horvath's most recent work demonstrates that the epigenetic clock captures aspects of biological age.