A Complex Systems View of the Biology of Aging

The study of complex systems, made up of many interacting parts, is a well-developed area of research and development, spanning many distinct disciplines of science and engineering. Any particular subset of cellular biology can be considered a complex system, and the tools developed in other disciplines can be adapted to use in the life sciences. Here, researchers discuss how to apply complex systems frameworks to the study of aging. This approach to develop means of intervention embraces the complexity of our biology. It is the polar opposite of, say, the SENS approach to rejuvenation, which seeks to work around that complexity (and the amount of work needed to understand it) by focusing on the comparatively narrow domain of the root causes of aging. If addressing causes, we do not need to fully understand all of the consequences of those causative mechanisms in detail, we just need to fix those causes.

The goals of aging biology research are broad and ambitious - to understand how a multitude of genes, pathways, and mechanisms at multiple scales contribute to declines in function, health and lifespan in ways that can vary across populations, environments and species. Enormous progress has been made identifying individual genes, pathways, molecules and their connection in mechanisms that modulate aging. However, there has been limited progress in our understanding of how these factors interact to produce a global set of aging processes, or in how these processes combine to produce functional phenotypes of aging such as frailty, or demographic patterns such as the Gompertz mortality curves found across the tree of life.

Accordingly, research is increasingly focusing on understanding how mechanisms and pathways integrate, drawing on concepts of complex systems such as resilience, homeostasis, networks, and interactions. This transition to a complex systems view of aging has been happening piecemeal and is only sometimes explicitly acknowledged; many of the core concepts and methods are unfamiliar to biologists and may be defined in various ways. Here, we provide a theoretical framework and introduction to the key concepts of complex systems theory as applied to aging, as a primer to orient researchers new to the field and in the attempt to offer a unifying vision for how a complex systems approach could be transformative in aging biology research.

Link: https://doi.org/10.1038/s43587-022-00252-6

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