WP2 – Human cohorts of aged persons

Objectives

Discover genes affecting healthspan in existing cohorts of aged persons (male and female) and
map them onto pathways.
We will use data from the participating cohorts and from C. elegans to identify genetic variants overrepresented
in cohorts of persons with unusually long healthspan (as distinct from lifespan), taking into account
sex and gender differences. From these variants, the most robust (occurring in several ageing cohorts) and
promising ones (e.g. coding polymorphisms, polymorphisms contributing the highest relative risk) will be
selected. Thus, we need to:
1. Identify the genetic variants responsible for long healthspan in the participating human cohorts
2. Correlate the above with the results from C. elegans
3. Identify the differences and similarities between 1&2 and evaluate the potential for both to reach the
objective 4 below.
4. Using the data produced by the other work packages, select a key set of genetic variants to be tested
independently

Deliverables (brief description and month of delivery)
D2.1. Collection of available genomics (and other omics) data in the cohorts (M6)
D2.2. Collection and harmonization of available phenotypic data in the cohorts of elderly (data on
morbidity from in-patient and out-patient registries, medication records, biochemistry, current
living conditions (home/elderly care) etc. (M9)
D2.3. Definition of healthy lifespan determinants available in the cohorts (M12)
D2.4. The key group(s) of healthy aged participants in the cohorts identified – establishment of the “Long Healthspan Cohort” (M20)
D2.5. The set of human loci determining healthy ageing internally reported (M24)
D2.6. The joint set of C.elegans findings and human data determined (M36)
D2.7. Analyses of the combined data (M40)
D2.8. Genotyping or sequencing of the replication material (M48)
D2.9. Interpretation of the results as determinants of healthspan (M55)
D2.10. Report of validated polymorphisms predictive of better (or worse) health in the aged, stratified by sex
and gender, and mapped onto pathways

Milestones
M2.1: Genome sequences of first sub-cohort of healthy aged analysed
M2.2: Findings replicated in independent cohort from different EU country