SAN FRANCISCO--(BUSINESS WIRE)--Two scientific papers published in today’s online issue of Nature mark a dramatic step forward in our understanding of the cellular details of aging.
One paper describes the first single cell aging atlas, a reference data set which reveals the detailed, aging related molecular changes in cells from many different tissues and organs in the mouse. This project, dubbed the Tabula Muris Senis, builds on the first Tabula Muris cell atlas, published in Nature in 2018, and is led by the Chan Zuckerberg Biohub, a nonprofit research organization where leaders in science and technology come together to drive discovery and support the bold vision, to cure, prevent or manage disease by the end of the century. The work was performed in collaboration with a large number of labs at Stanford and UCSF.
The second paper, also a collaboration between the Chan Zuckerberg Biohub and Stanford University, provides a description of which genes change with age at the level of bulk tissues, also across a large number of organs and tissues, and helps bridge the single cell insights with more traditional approaches to genomic analysis.
While the mouse genome provides a theoretical blueprint to how the organism develops, in practice it is very challenging to interpret. The single cell atlas can be thought of as a companion to the genome which provides substantially new insight into how different cell types, all of which contain the same DNA, make different use of the genome to perform specialized functions. The two papers are a bio-molecular gold mine for medical researchers for their content and the technological tools leveraged for analysis. By being able to identify health at the cellular level (as explored in the first paper) and in tissue composition (as described in the second paper) researchers were able to track changes over time, marking a significant step forward in the science of aging.
Because the mouse is the most commonly used animal model in the development of new drugs and therapies worldwide, this detailed characterization of cellular changes over time will empower future research and could have a global impact on age-related illness such as heart disease and diabetes. Specifically, the researchers discovered that with age, antibody-secreting plasma cells infiltrate diverse organs where they are usually never found: kidney, heart, liver, muscle, fat, lung, and thymus. By understanding the behavior of the body, scientists will now be better equipped to understand disease onset and develop intervention strategies that can slow the progression of disease.
“This research was possible because of the CZ Biohub’s unique relationship with Stanford and UCSF, where multiple specialists from diverse fields came together to catalyze discoveries that wouldn’t be possible in any individual lab,” said Co-President Stephen Quake. “I am proud of the years of work put in by this ground-breaking team and what we’ve done together to advance the study of aging.”
“Tabula Muris Senis is poised to inform and impact science on a global scale,” said senior author Tony Wyss-Coray, D. H. Chen Professor of Neurology at Stanford. “To date, no one has compared the rate of aging between organs. We did so and found that adipose tissues undergo the earliest, and most dramatic, changes. To date, no one has determined if organs age in the same way. We did so and uncovered several common themes, and also showed that these hallmarks undergo the most drastic changes in adipose tissues.”
The first paper, entitled “A single-cell transcriptomic atlas characterizes ageing tissues in the mouse”, includes a comprehensive overview at single cell resolution of 23 tissues, which has not been done before at this scale and across such a large collection of tissues from single animals. The new content goes beyond the 2018 Tabula Muris research to demonstrate the progression of cell types during the life span at single cell resolution, allowing researchers to explore changes in composition over six key intervals, and start to understand why and how some organs age differently than others. The research for Tabula Muris Senis commenced after the initial Tabula Muris research in 2018 and paired specialties across sequencing, computational biology and technology development.
The second paper, “Ageing hallmarks exhibit organ-specific temporal signatures”, profiles across 10 time points of the mouse life both organ RNA changes and blood protein changes. While the first paper focused on single cell expression, this content studies bulk tissue samples and their change in broader composition.
About the Chan Zuckerberg Biohub
The Chan Zuckerberg Biohub is a nonprofit research organization setting the standard for collaborative science, where leaders in science and technology come together to drive discovery and support the bold vision to cure, prevent or manage disease by the end of the century. The CZ Biohub seeks to understand the fundamental mechanisms underlying disease and to develop new technologies that will lead to actionable diagnostics and effective therapies. The CZ Biohub is a regional research endeavor with international reach, where the Bay Area’s leading institutions — the University of California, Berkeley, Stanford University and the University of California, San Francisco — join forces with the CZ Biohub’s innovative internal team to catalyze impact, benefitting people and partnerships around the world. To learn more, visit CZBiohub.org.