Abstract
The molecular basis of aging and of aging-related diseases is being unraveled at an increasing pace. More recently, a long healthspan is seen as an important goal. However, a precise definition of health and healthspan is not straightforward, and the causal molecular basis of health “per se” is largely unknown. Here, we define health based on 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. Clusters of these genes based on molecular interaction and annotation data give rise to maps of healthspan pathways for humans, featuring the themes transcription initiation, proliferation and cholesterol/lipid processing, and for C. elegans, featuring the themes immune response and the mitochondrion. Overlaying healthspan-related gene expression data (describing effects of metabolic intervention associated with improvements in health) onto the aforementioned healthspan pathway maps, we observe the downregulation of Notch signalling in humans and of proliferation/cell-cycle in C. elegans; the former reflects the proinflammatory role of the Notch pathway. Investigating the overlap of healthspan pathways of humans and 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, is available as a reference for future investigations, at http://www.h2020awe.eu/index.php/pathways/.
Footnotes
↵* co-first authors.
