Untangling Aging Using Dynamic, Organism-Level Phenotypic Networks
1Calico Life Sciences, LLC, South San Francisco, CA 94080, USA.
Abstract:
Research on aging requires the ability to measure aging, and therein lies a challenge: it is impossible to measure every molecular, cellular, and physiological change that develops over time, but it is difficult to prioritize phenotypes for measurement because it is unclear which biological changes should be considered aspects of aging and, further, which species and environments exhibit "real aging." Here, I propose a strategy to address this challenge: rather than classify phenotypes as "real aging" or not, conceptualize aging as the set of all age-dependent phenotypes and appreciate that this set and its underlying mechanisms may vary by population. Use automated phenotyping technologies to measure as many age-dependent phenotypes as possible within individuals over time, prioritizing organism-level (i.e., physiological) phenotypes in order to enrich for health relevance. Use those high-dimensional phenotypic data to construct dynamic networks that allow aging to be studied with unprecedented sophistication and rigor.
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