Life resists chemistry not conditions.

Extremophiles are used to study both the limits of life and its potential elsewhere. Categories are commonly employed to describe extreme conditions, however, changing the focus to the underlying chemical alterations of cellular biomolecules permits a clearer delineation of the limits of life. This also provides a common basis for interdisciplinary studies of life in extreme environments intersecting biology, chemistry, geology, environmental and planetary sciences. Using this perspective, four general principles can be drawn from the past decades of research into extremophiles: 1-Microbial survival after exposure to environmental stressors is challenged by damage incurred at the molecular level, 2-Damage-susceptibility of cellular (macro)molecules vary by structure, chemical composition, and surrounding molecules, 3-Local physicochemical states alter the chemistry underpinning microbial survival, and 4-The same macromolecular chemical and/or structural damages produced by different stressors can be resisted by the same cellular mechanisms. These general principles provide a common basis for interdisciplinary studies of the limits of life. This chemistry-focused approach has implications for defining the limits of life, paleoenvironment reconstruction, site selection for sampling, and choice of appropriate model systems for development of detection methods for microbial cells and extraction of molecules. This approach also contributes to the field of astrobiology, constraining the concept of habitability in the solar system and exoplanets. Descriptive terms are useful in science, but for extremophile microbiology and astrobiology, it is useful to recognize that life resists chemistry, not conditions.