Leiden Longevity Study follow-up study

The Leiden Longevity Study was initiated in 2002, in which a total of 421
families were enrolled based on their extreme longevity, defined by the
presence of two living siblings including men >89 years and women >91 years
(generation F1). The aim is to study the genetic determination of human
longevity and disease in old age. Moreover, the offspring (N=1,750) of these
long-lived siblings and their current partners (N=776) were recruited
(generation F2) to study phenotypic characteristics of longevity and
physiological mechanisms protecting from disease. We are now planning a new
follow-up study, 19 years after initiating the Leiden Longevity Study, and
include a selection of the F2 generation, who were aged 60 years on average at
inclusion. Since we already have a rich dataset of (genotypic and) phenotypic
characteristics of the F2 generation from 19 years ago and for some
participants also from 13-15 and/or 11-12 years ago, we primarily aim to
investigate differences in phenotypic changes over time in these individuals
(e.g. physical and cognitive performance) and relate these to health biomarkers
generated from baseline measurements and the changes in these biomarkers over
time.

We aim to study individual changes in phenotypic characteristics of
cardio-metabolic health, and of cognitive and physical performance over a time
span of 11 to 19 years in older individuals previously included in the Leiden
Longevity Study. This allows us to establish individual age trajectories of the
phenotypic characteristics where in the past we only used observations of
single timepoints. Due to the rich baseline data we will be able to study
whether baseline health markers (genetic traditional clinical variables as well
as novel biomarker algorithms based on genetics, metabolomics and DNA
methylation) predict any or all of the phenotypic changes and whether we can
improve these algorithms. We will
1) establish the variability of change in these phenotypic characteristics over
time and to what extend these associate with each other;
2) establish whether such phenotypic changes associate with variation in
biomarker levels, such as those of gut health, to be measured in this follow up
study;
3) establish whether novel biomarker algorithms constructed from variables
measured at baseline and/or across different timepoints associate to the
phenotypic changes and/or to gut health;
4) establish whether these changes over time depend on longevity propensity by
comparing offspring of long-lived families and their partners;
5) establish the relation of phenotypic changes to future mortality and
(co)morbidity.

This study is an observational nested case-control family-based follow-up study
which includes a selection of 500 participants, consisting of members of a
family enriched for longevity (cases) and their partners (controls). This study
consists of questionnaires and collecting biomaterials at home and phenotypic
measurements at the research center.

There are no direct benefits to the subjects. We ask the participants to
collect a sample of their urine and stool, which may be of some discomfort. We
include some questionnaires about well-being, anxiety, and depression, which
might be experienced as burdensome for some participants. There is one visit to
the research center of approximately three hours. Blood withdrawal of 8 tubes
with in total 64.5 mL will be performed, which is a minimally invasive
procedure. Cognitive tests might be confronting for some of the participants.