Abstract
The molecular basis of aging and of aging-associated diseases is being unraveled at an increasing pace. An extended healthspan, and not merely an extension of lifespan, has become the aim of medical practice. Here, we define health based on the absence of diseases and dysfunctions. Based on an extensive review of the literature, in particular for humans and C. elegans, we compile a list of features of health and of the genes associated with them. These genes may or may not be associated with survival/lifespan. In turn, survival/lifespan genes that are not known to be directly associated with health are not considered. Clusters of these genes based on molecular interaction data give rise to maps of healthspan pathways for humans and for C. elegans. Overlaying healthspan-related gene expression data onto the healthspan pathway maps, we observe the downregulation of (pro-inflammatory) Notch signaling in humans and of proliferation in C. elegans. We identify transcription, proliferation/biosynthesis and lipids as a common theme on the annotation level, and proliferation-related kinases on the gene/protein level. Our literature-based data corpus, including visualization, should be seen as a pilot investigation of the molecular underpinnings of health in two different species. Web address: http://pathways.h2020awe.eu.
Highlights
For a long time, an active, targeted intervention to maintain health into old age was terra incognita
We find that if we construct an overlap between the healthspan pathways in C. elegans and humans, genes involved in transcription, proliferation/biosynthesis and lipids are www.aging-us.com highlighted, but this overlap is not straightforward to interpret in the light of the independent health-related gene expression data that we used to test plausibility of the single-species healthspan pathway maps
We describe the healthspan pathway maps in detail, in light of gene expression data that we overlaid onto the pathway maps
Summary
An active, targeted intervention to maintain health into old age was terra incognita. We compile lists of genes associated with health based on the literature, for humans and C. elegans We organize these genes into maps of healthspan pathways, based on gene/protein interaction and annotation data. A lack of dysfunction exemplified by stress resistance, locomotion, pharyngeal pumping and reproduction are taken as the key health features in C. elegans [31] On this basis, a core set of 11 genes is directly implicated in improvements of locomotion by genetics, and another set of 20 genes is indirectly implicated in improvements of the key health features by studies that investigate effects of compounds (see Supplementary Tables 4, 5). All healthspan pathways discussed in this manuscript, as well as the overlaps we found between species, are available for interactive exploration at http://pathways.h2020awe.eu
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