Radiological, cognitive and dynamic behavioural phenotyping of offspring from longlived siblings and their partners

In the IOP genomics project (IGE01014A) *The genetic determination of longevity
and disease in old age* (CME protocol P01.113) we have enrolled 450 families
into the Leiden Longevity Study based on their extreme longevity. We recruited
sibling pairs aged 90 years (generation F1), the children from the long-living
subjects (generation F2) and the partners of the children of the long-living
subjects (generation F2). The recruitment algorithm we used in that study has
resulted in families enriched for genetic factors for longevity. The children
from the long-living subjects (F2 generation) are therefore genetically
predisposed to become long-lived, while their partners have a mortality risk
comparable to the general population. In the IOP project (IGE5007, CCMO-number
NL11749.058.06) *Biomarkers of the rate of ageing* (LUMC CME protocol P06.059)
we focussed on biochemical and cellular characteristics of the F2 generation. A
total of 340 couples (children of the long-living subjects and their partners)
were characterised by a genome wide association study, serum levels of key
metabolic and endocrine parameters, metabolomic and glycomic profiles, and a
genome wide gene expression array. Amongst others, we found that children of
the long-living subjects had better metabolic control compared to their
spouses. In 2008, the Netherlands Consortium of Healthy Ageing (NCHA), a
collaborative effort of Erasmus Medical Center Rotterdam and Leiden University
Medical Center, was founded. In the realm of this consortium, F2 subjects of
the Leiden Longevity Study will be phenotyped for signs and symptoms of
age-related diseases. This will enable us to link the already available
biochemical and cellular characteristics to these ageing phenotypes.
Furthermore, this will also create the possibility of validation of significant
associations obtained in the Rotterdam Study within the Leiden Longevity Study.

The objective of this study is to phenotype (radiological, cognitive, and
dynamic behavourial) offspring of long-living subjects of the Leiden Longevity
Study and their partners.

Cross-sectional case-control study

This is an observational study in which subjects undergo a CT-heart (radiation
exposure approximately 2 mSv) and a X-ray of the hands (Radiation exposure less
than 0.001 mSv).