Healthspan pathway maps in C. elegans and humans highlight transcription, proliferation/biosynthesis and lipids

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 .

Genes implicated in Caenorhabditis elegans and human health regulate stress resistance and physical abilities in aged Caenorhabditis elegans

“…The downregulation of sad-1 did not significantly affect the performance of the worms, which might be related to poor RNAi efficiency. In conclusion, eight of the nine genes implicated in healthspan were shown to be relevant for physical and/or physiological function, in line with Möller et al [7]. The mean values ± s.e.m.…”

“…Recently, we calculated 'healthspan pathway maps' and their overlap in humans and C. elegans [7]. To compile the maps, we first defined healthspan as the time spent in the absence of disease and dysfunction [8].…”

Knock-down of odr-3 and ife-2 additively extends lifespan and healthspan in C. elegans

“…Longevity is regulated by a combination of genetic and non-genetic factors, such as environmental interactions and lifestyle. The identification of genetic mutations that extend lifespan in model organisms has shown that longevity is mainly regulated by a complex interplay between many signaling pathways that affect cellular functions as diverse as nutrient sensing, genome stability, mitochondria fitness, organelle proteostasis, intercellular communication, transcription, proliferation and cellular regeneration [ 58 , 59 ]. Previously, we have successfully used network-based approaches, building upon the list of known longevity-associated genes hosted in the GenAge database [ 9 ], to predict novel genetic or drug interventions that extend lifespan [ 60 , 61 ].…”

Towards biomarkers for outcomes after pancreatic ductal adenocarcinoma and ischaemic stroke, with focus on (co)-morbidity and ageing/cellular senescence (SASKit): protocol for a prospective cohort study

“…The longitudinal transcriptomics of the patients and the controls may also be analysed integratively based on the ‘optimal discovery procedure’, 87 considering, however, that landmark feature data can only be used to predict events after the landmark. Finally, we will map the differential omics data onto a human ‘healthspan pathway map’, 88 that is, a set of clusters/pathways based on health-related genetic data that we assembled recently.…”