Cellular Senescence in Health, Disease and Aging: Blessing or Curse?

Abstract

Cover image courtesy of Markus Riessland © 2021 by the authors. Articles in this book are Open Access and distributed under the Creative Commons Attribution (CC BY) license, which allows users to download, copy and build upon published articles, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. About the EditorRiessland, Markus is a trained molecular biologist with a background in neuroscience, human genetics and neurodegenerative diseases. Dr. Riessland received his PhD from the Clinic of the University of Cologne, Institute for Human Genetics, Germany. Early in his career, Dr. Riessland was involved in several internationally funded projects, where he performed and published studies on epigenetic modifiers as a potential therapy for the neurodegenerative disease spinal muscular atrophy (SMA). His research is particularly focused on the identification and characterization of neuron-specific disease-modifying factors that may facilitate the development of novel therapeutic strategies for degenerative disorders of the central nervous system. Dr. Riessland focuses on the understanding of cellular senescence. Cellular senescence is a common biological process in which mitotic cells may shut down the cell cycle when they recognize they have suffered DNA damage during division. This process causes a generation of "undead cells" (also known as "Zombie Cells"). This helps to prevent damaged cells from growing uncontrollably and causing problems such as cancer. Undead cells are, in fact, common and they are found all over the body. However, senescence is not typically seen in the nerve cells of the brain. Unlike most other cells in the body, neurons stop dividing once they are fully formed. In the lab of Nobel Laureate Paul Greengard at Rockefeller University, Dr. Riessland discovered that, surprisingly, post-mitotic dopaminergic neurons-which regulate motivation, memory, and movement by producing the chemical messenger dopamine-can nevertheless become senescent. This finding could have widespread implications for the understanding of many age-related neurodegenerative disorders (e.g., Parkinson's disease) and the aging process itself. Currently, his lab in the Center for Nervous System Disorders at the Department of Neurobiology and Behavior at Stony Brook University uses stem cell-based approaches as well as mouse models and next generation sequencing techniques (TRAP-seq, RNA-seq, ATAC-seq, scRNA-seq, etc.) to tackle the questions where and how cellular senescence in the brain could occur and spread, which cell types are involved and what the molecular triggers are. Additionally, research in the lab focuses on the identification and molecular characterization of genetic modifiers that influence the vulnerability of neuronal subtypes. The knowledge of molecular modifiers helps us to understand the underlying reasons of vulnerability that could be leveraged to protect cells from neurodegeneration. Moreover, the lab's research aims to in...