Abstract

BackgroundCaloric 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.ResultsExpression 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.ConclusionsBased 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.Trial registrationClinicalTrials.gov, NCT00561145Electronic supplementary materialThe online version of this article (doi:10.1186/s12263-016-0528-0) contains supplementary material, which is available to authorized users.

Highlights

  • Caloric restriction (CR) is considered to increase lifespan and to prevent various age-related diseases in different nonhuman organisms

  • Before the start of the 30 % CR diet, the expression of genes involved in immune response was higher in old compared to young men and the expression of genes involved in RNA processing was lower in old compared to young men (Table 3)

  • We aimed to investigate the potential relevance of age at which CR should be implemented to be most effective on gene expression changes of pathways important for healthy aging

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Summary

Introduction

Caloric restriction (CR) is considered to increase lifespan and to prevent various age-related diseases in different nonhuman organisms. 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. CR did increase longevity in monkeys at the Wisconsin National Primate Research Centre [6] but did not increase longevity in monkeys at the National Institute of Aging [20] Factors such as genetics, husbandry, or dietary composition are perhaps more relevant for longevity in these primate studies than the number of calories [20]. The limited number of studies investigating the effect of a CR diet in humans is, because of long life expectancy [27], solely directed at beneficial health effects and not at longevity [15]. 6 years of CR decreased risk factors for atherosclerosis

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