The following work was performed:
1. A project website was set up (with a publicly accessible and a private section only accessible to project participants) and a position paper was published to bring the project to the attention of the scientific community.
2. Genome-wide association studies based on SNP-arrays have been carried out on in groups of over 70-year old individuals in good health, compared to a control group with similar characteristics but suffering from health problems. The individual were recruited from existing cohorts in Finland, Estonia and Sweden.
3. A new automated instrument (WormCAMP) for screening healthspan in C. elegans was developed, as a successor to the initial WorMotel, as well as improved measures for healthspan (maximum velocity after stimulation with a blue light flash).
4. RNAi screening for healthspan was validated on the WormCAMP, and over 3700 genes have been tested so far by RNAi knock-down. A number of these have a differential effect on lifespan versus healthspan.
5. A reporter panel, consisting a set of genetic C. elegans strains expressing GFP-reporters to monitor the activation of 8 cytoprotective signalling pathways, was created.
6. AnalytiCon Discovery has provided pure natural products, fractions from edible plants and 11 organic - as well as aqueous extracts from 11 carefully selected TCM plants with reported anti-ageing effects. Moreover, fractions were generated from the active organic extracts of the TCM plants by separation on silica gel columns. So far, 427 samples have been analysed for healthspan effects in C. elegans, and from one TCM plant with clear activity, bioassay-guided purification has led to active compounds.
7. Adult human skin fibroblasts PCP1 and hTERT-MSC stem cell cultures were used to study long-term (> 375 days) effects of rapamycin on the survival, lifespan, stress tolerance, telomere length and global DNA methylation. Three pure compounds were provided by AnalytiCon Discovery and tested on PCS cells for short-term effects (up to 10 days) with a wide range of concentrations (between 1 nM to 200 mM). Biphasic hormetic dose responses were observed for cell toxicity, growth, proliferation, stress tolerance.
8. Two pure compounds were tested for short-term (2-3 month) and longer-term effects on ageing in male and female 24-month-old C57 mice.
9. Based on bioinformatics an data mining analyses, a healthspan pathway map was inferred.
10. Abiomics prepared several data analysis models.
11. Agilent Technologies developed algorithms to analyse large cohorts of NGS and CNV data.
