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Interaction Analysis of Longevity Interventions Using Survival Curves

Systems Biology of Ageing Cologne (Sybacol), University of Cologne, 50931 Cologne, Germany
Institut für Theoretische Physik, Universität zu Köln, 50937 Cologne, Germany
MBR Optical Systems, 42279 Wuppertal, Germany
Department of Physics, Indian Institute of Technology Delhi, Hauz Khas, 110016 New Delhi, India
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Received: 24 November 2017 / Revised: 30 December 2017 / Accepted: 3 January 2018 / Published: 6 January 2018
(This article belongs to the Special Issue Systems Biology of Aging)
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A long-standing problem in ageing research is to understand how different factors contributing to longevity should be expected to act in combination under the assumption that they are independent. Standard interaction analysis compares the extension of mean lifespan achieved by a combination of interventions to the prediction under an additive or multiplicative null model, but neither model is fundamentally justified. Moreover, the target of longevity interventions is not mean life span but the entire survival curve. Here we formulate a mathematical approach for predicting the survival curve resulting from a combination of two independent interventions based on the survival curves of the individual treatments, and quantify interaction between interventions as the deviation from this prediction. We test the method on a published data set comprising survival curves for all combinations of four different longevity interventions in Caenorhabditis elegans. We find that interactions are generally weak even when the standard analysis indicates otherwise. View Full-Text
Keywords: models of ageing; longevity interventions; epistasis; survival curves; failure time analysis; Caenorhabditis elegans models of ageing; longevity interventions; epistasis; survival curves; failure time analysis; Caenorhabditis elegans

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Nowak, S.; Neidhart, J.; Szendro, I.G.; Rzezonka, J.; Marathe, R.; Krug, J. Interaction Analysis of Longevity Interventions Using Survival Curves. Biology 2018, 7, 6.

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