Loss of epigenetic information as a cause of mammalian aging.

All living things experience an increase in entropy, manifested as a loss of genetic and epigenetic information. In yeast, epigenetic information is lost over time due to the relocalization of chromatin-modifying proteins to DNA breaks, causing cells to lose their identity, a hallmark of yeast aging. Using a system called "ICE" (inducible changes to the epigenome), we find that the act of faithful DNA repair advances aging at physiological, cognitive, and molecular levels, including erosion of the epigenetic landscape, cellular exdifferentiation, senescence, and advancement of the DNA methylation clock, which can be reversed by OSK-mediated rejuvenation.

Emerging Role of Translational Digital Biomarkers Within Home Cage Monitoring Technologies in Preclinical Drug Discovery and Development.

In drug discovery and development, traditional assessment of human patients and preclinical subjects occurs at limited time points in potentially stressful surroundings (i.e., the clinic or a test arena), which can impact data quality and welfare.

Biomonitoring and Digital Data Technology as an Opportunity for Enhancing Animal Study Translation.

The failure of animal studies to translate to effective clinical therapeutics has driven efforts to identify underlying cause and develop solutions that improve the reproducibility and translatability of preclinical research. Common issues revolve around study design, analysis, and reporting as well as standardization between preclinical and clinical endpoints. To address these needs, recent advancements in digital technology, including biomonitoring of digital biomarkers, development of software systems and database technologies, as well as application of artificial intelligence to preclinical datasets can be used to increase the translational relevance of preclinical animal research.

Digital Biomarkers Enable Automated, Longitudinal Monitoring in a Mouse Model of Aging.

To understand the growing needs of an aging human population, there is demand for scalable and reproducible approaches to study animal models of aging and to test novel therapeutic interventions. We investigated the sensitivity and utility of a continuous monitoring platform and its digital biomarkers (motion, breathing rate, and wheel running) to evaluate behavioral and physiological differences between "young" (12 weeks) and "old" (23 months) male C57BL/6J mice with or without running wheels in the home cage. Compared to young mice, old mice showed marked reductions in motion and breathing rate, as well as altered circadian rhythms.