Loss of functionality is ubiquitous across Nature, from aging in organisms to the decay of human engineered systems. With time, plants and animals lose functionality and die, mountains erode, buildings and devices structurally fail and decay. In many nonliving systems general principles have been articulated that govern this loss of functionality and these may be applicable to aging. In biological systems, however, a multitude of scenarios and myriads of mechanisms have been proposed to explain the deterioration of the architecture and function of organisms. We are convinced that looking at mammalian aging from a systems level viewpoint is a critical component in the search for general principles and “levers” that control the system, including the paths to alter the processes leading to aging. A vast amount of experimental data has been accumulated and, with the development of better experimental techniques during the past 20 years, quantitative data is being collected that can be used to design further experiments and develop quantitative theories of aging. However, our experience in physics is that when we integrate the details of sub-system dynamics into a more holistic systems level approach and search for underlying principles that govern physical processes we gain deeper insight into developing falsifiable theoretical understandings of Nature. We believe that the same methodology may provide new and important insights into understanding biological aging. Motivated by the above observations we invite you to a two-day interdisciplinary workshop to discuss mammalian aging.