Differences in genome-wide gene expression response in peripheral blood mononuclear cells between young and old men upon caloric restriction

I. P. G. Van Bussel, A. Jolink-Stoppelenburg, C. P. G. M. De Groot, M. R. Müller, L. A. Afman

Caloric restriction (CR) is considered to increase lifespan and to prevent various age-related diseases in different nonhuman organisms. Only a limited number of CR studies have been performed on humans, and results put CR as a beneficial tool to decrease risk factors in several age-related diseases. The question remains at what age CR should be implemented to be most effective with respect to healthy aging. The aim of our study was to elucidate the role of age in the transcriptional response to a completely controlled 30 % CR diet on immune cells, as immune response is affected during aging. Ten healthy young men, aged 20-28, and nine healthy old men, aged 64-85, were subjected to a 2-week weight maintenance diet, followed by 3 weeks of 30 % CR. Before and after 30 % CR, the whole genome gene expression in peripheral blood mononuclear cells (PBMCs) was assessed. Expression of 554 genes showed a different response between young and old men upon CR. Gene set enrichment analysis revealed a downregulation of gene sets involved in the immune response in young but not in old men. At baseline, immune response-related genes were higher expressed in old compared to young men. Upstream regulator analyses revealed that most potential regulators were controlling the immune response. Based on the gene expression data, we theorise that a short period of CR is not effective in old men regarding immune-related pathways while it is effective in young men. ClinicalTrials.gov, NCT00561145.