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BACKGROUND: Recent advances in medical care have increased life expectancy and improved the quality of life for people with Down syndrome (DS). These advances are the result of both pre-clinical and clinical research but much about DS is still poorly understood. In 2020, the NIH announced their plan to update their DS research plan and requested input from the scientific and advocacy community. OBJECTIVE: The National Down Syndrome Society (NDSS) and the LuMind IDSC Foundation worked together with scientific and medical experts to develop recommendations for the NIH research plan. METHODS: NDSS and LuMind IDSC assembled over 50 experts across multiple disciplines and organized them in eleven working groups focused on specific issues for people with DS. RESULTS: This review article summarizes the research gaps and recommendations that have the potential to improve the health and quality of life for people with DS within the next decade. CONCLUSIONS: This review highlights many of the scientific gaps that exist in DS research. Based on these gaps, a multidisciplinary group of DS experts has made recommendations to advance DS research. This paper may also aid policymakers and the DS community to build a comprehensive national DS research strategy.

Cell senescence, the permanent withdrawal of a cell from the cell cycle, is characterized by dramatic, cytological scale changes to DNA condensation throughout the genome. While prior emphasis has been placed on increases in heterochromatin, such as the formation of compact Senescent Associated Heterochromatin Foci (SAHF) structures, our recent findings showed that SAHF formation is preceded by the unravelling of constitutive heterochromatin into visibly extended structures, which we have termed Senescent Associated Distension of Satellites or SADS. Interestingly, neither of these marked changes in DNA condensation appear to be mediated by changes in canonical, heterochromatin-associated histone modifications. Rather, several observations suggest that these events may be facilitated by changes in LaminB1 levels and/or other factors that control higher-order chromatin architecture. Here, we review what is known about senescence-associated chromatin reorganization and present preliminary results using high-resolution microscopy techniques to show that each peri/centromeric satellite in senescent cells is comprised of several condensed domains connected by thin fibrils of satellite DNA. We then discuss the potential importance of these striking changes in chromatin condensation for cell senescence, and also as a model to provide a needed window into the higher-order packaging of the genome.

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