The role of low-grade inflammation and metabolic flexibility in aging and nutritional modulation thereof: A systems biology approach

https://doi.org/10.1016/j.mad.2014.01.004Get rights and content
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Highlights

  • Aging is associated with low-grade inflammation and metabolic dysfunction.

  • Modeling can help to understand the dynamics of such processes and to modulate them.

  • Integration of inflammation and metabolism happens at various time and space scales.

  • Mechanistic information is not available at each scale.

  • Multiscale modeling with both mechanistic and black-box type models is thus necessary.

Abstract

Aging is a biological process characterized by the progressive functional decline of many interrelated physiological systems. In particular, aging is associated with the development of a systemic state of low-grade chronic inflammation (inflammaging), and with progressive deterioration of metabolic function. Systems biology has helped in identifying the mediators and pathways involved in these phenomena, mainly through the application of high-throughput screening methods, valued for their molecular comprehensiveness. Nevertheless, inflammation and metabolic regulation are dynamical processes whose behavior must be understood at multiple levels of biological organization (molecular, cellular, organ, and system levels) and on multiple time scales. Mathematical modeling of such behavior, with incorporation of mechanistic knowledge on interactions between inflammatory and metabolic mediators, may help in devising nutritional interventions capable of preventing, or ameliorating, the age-associated functional decline of the corresponding systems.

Keywords

Inflammaging
Metabolic flexibility
Nutrition
Systems biology
Mathematical model

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