FIT to Grow Old - Functionality of the Immune System and Healthy Aging

Rationale: Aging is commonly associated with reduced functionality of the immune system, resulting in a higher prevalence of infectious disease, auto-immune disease, cancer, and low-er 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 profiles 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, identifying individuals with reduced immune cell fitness will be crucial.

Objective: The primary aim of this study is to extensively characterize immune cell fitness in the elderly population 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 study the effects of metabolites and nutrients on their ability to improve immune cell fitness in monocytes from the elderly.

Study design: The study will be a cross-sectional study in which we will compare the immune cell fitness state of elderly people using young adult people to define an 'immune fit' status. Immune cell fit-ness will be measured in monocytes, which will be obtained from blood samples. Subjects will be given a standardized meal which they consume in the evening before the study visit at latest 8.00 pm. After consumption of the meal, subjects are not allowed to eat or drink anything but water.

On the study day, before the start of blood sampling, a small blood sample via a finger prick is collected to measure CRP levels. CRP levels of ≥10.0 mg/L indicate severe infection and will consequently exclude the subject from participating on that specific day. The relevant subjects are asked to make a new appointment. If CRP levels are < 10 mg/L, blood sampling will continue.

Blood sampling and anthropometric measurements including body weight, waist and hip circumference and a DEXA scan will be performed in each subject, after which the subjects will receive breakfast. Subjects will fill in an FFQ to gain insights into regular dietary intake. In addition, subjects will fill in questionnaires on sleep quality and general health.