ABS 2022
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The ticking clock, a molecular behavior study of a Urochordate linking aging to circadian regulation  
Yotam Voskoboynik1,2, Aidan Glina1,2, Marky Kowarsk3, Chiara Anselmi2,4, Norma F Neff5, Katherine J Ishizuka2,4, Karla J Palmeri2,4, Tom Levy2,4, Stephen R Quake5,6, Irving L Weissman2,4,5, Debashis Sahoo8,9, Ayelet Voskoboynik2,4,5, Rachel Ben-Shlomo7. 1Bioinformatics and System Biology, Jacobs School of Engineering, University of California San Diego , San Diego, La Jolla, California, United States; 2Hopkins Marine Station Stanford University, Pacific Grove, California, United States; 3Department of Physics, Stanford University, Stanford, California, United States; 4Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California, United States; 5Chan Zuckerberg Biohub, San Francisco , California, United States; 6Departments of Applied Physics and Bioengineering, Stanford University, Stanford, California, United States; 7Department of Biology and Environment, Faculty of Natural Sciences, University of Haifa-Oranim, Tivon, , Israel; 8Department of Pediatrics, University of California San Diego, La Jolla, California, United States; 9Department of Computer Science and Engineering, Jacob's School of Engineering, University of California San Diego, La Jolla, California, United States

Organisms can and do measure astronomical time using biological timers. These pacemakers not only measure time, they also generate adaptive rhythms in behavior and physiology that have evolved in response to these environmental perturbations. The most studied molecular biological timer is the circadian oscillator that regulate 24-hour cycles. Expression levels of circadian clock genes, have been shown to change with age. Using the colonial Urochordate Botryllus schlosseri, a long-lived organism we studied the link between aging and circadian gene expression. We characterize global gene expression changes across time and age and link them to aging phenotypes. Our analyses revealed that B. schlosseri clock and clock-controlled genes oscillate daily with age-specific amplitudes and frequencies. These age-related patterns persist at the tissue level, where dramatic variations in the cyclic gene expression link to morphological and physiological aging phenotypes. The molecular clock atlas we developed suggests alterations in circadian gene expression as a key regulator of aging, linking stem cell aging and loss of regenerative potential with molecular decline of circadian regulation.