the FIT to Grow Old study - functionality of the immune system and healthy aging

Aging is commonly associated with reduced functionality of the immune system,
resulting in a higher prevalence of the infectious disease, auto-immune
disease, cancer, and lower efficiency of vaccination. The reduction in immune
functionality is called *immunosenescence* and is often observed in addition to
a chronic state of systemic inflammation, referred to as *inflammaging*. It is
commonly believed that strategies improving immune functionality can be applied
to improve healthy aging. Nutritional strategies, in particular, receive
increasing attention, as several foods and nutrients are shown to exert
immunomodulatory properties. Nutritional strategies focussing on the intake of
polyunsaturated fatty acids have indeed shown improvements in cytokine profile
and inflammatory gene expression but suffer from large inter-individual
variation, which might be caused by differences in immune functionality. Recent
studies within the field of immunometabolism have shown that immune
functionality is largely dependent on intracellular metabolism, leading to the
introduction of the new term * immune cell fitness* which combines the
metabolic and functional status of an immune cell. To improve the efficiency of
immunomodulatory nutritional intervention strategies and work towards
personalized approaches to support healthy aging, the identification of
individuals with reduced immune cell fitness will be crucial.

During recent years the elderly*s immune system has drawn much attention by
researchers as a target to improve quality of life during aging. Most research
has focussed on the adaptive immune system, but knowledge of the innate immune
system is lacking. Furthermore, the phenomena of inflammaging and
immunosenescence are often present in the elderly but the meaning of these on a
functional and metabolic level is poorly understood. Increased understanding of
immune cell fitness in elderly and differences between individuals would be
highly valuable for the application of personalized nutritional strategies to
improve healthy aging. Therefore, the primary aim of this study is to
extensively characterize immune cell fitness in the elderly population in order
to distinguish immunologically fit elderly from the unfit. Since immune cell
fitness is a new concept, we will define a good immune cell fitness state using
a young adult study population. Using a follow-up visit, we will evaluate
whether our measure of immune cell fitness is robust and stable over time.
Furthermore, to identify potential nutritional strategies to improve immune
cell fitness and work towards personalized approaches, we will identify
metabolites or nutrients with the ability to improve immune cell fitness in the
elderly.

The study will be a cross-sectional study in which we will compare the immune
fitness state of elderly people using young people as a positive control to
define an *immune fit* status. Blood samples will be drawn after an overnight
fast. Subjects will be given a standardized meal in the evening before and are
not allowed to eat or drink anything but water after 20.00 h in the evening.
Before the start of blood sampling, a small blood sample is collected to
measure CRP levels. CRP levels of >=10.0 mg/L are considered to indicate severe
infection and will consequently exclude the subject from participating that
specific day. The relevant subjects are asked to make a new appointment. If CRP
levels are repeatedly >=10.0 mg/L, the participant is excluded from further
participation. The medical investigator will inform both the participant and
the corresponding general practitioner. If CRP levels are < 10 mg/L, blood
sampling will continue.
After blood sampling, anthropometric measurements including body weight and
body height will be performed with each subject. A DEXA-scan will be performed
to get insight into fat distribution since different fat depots can have
different effects on the immune system. After anthropometric measurements,
subjects will receive breakfast. Additionally, during the visit all subjects
will fill in an FFQ and questionnaires on general health and sleep quality.
After the characterization of the immunological fitness of each subject, only
the elderly subjects are invited for a second study visit, which is identical
to the first study visit. This blood sample will be used for an ex-vivo
screening of potential immunomodulatory nutrients and metabolites which
requires knowledge on the immunological state of the blood cells. The elderly
population will be invited for the second visit at least 6 months and the
latest 18 months after the first visit.

Burden and potential risks by study procedures are estimated to be minor. The
subject could experience mild pain by the venipuncture, which occasionally
leads to feeling light-headed and fainting. The subject will sit on a chair
during blood collection. A venipuncture could occasion-ally also lead to local
hematoma.