Unpicking the links between dietary restriction and ageing
The effects of reduced food consumption and lifespan extension have been observed in many species, including primates, but the biology behind how this is achieved is poorly understood. Researchers at the Max Planck Institute for Biology of Ageing, Cologne, Germany, the Cluster of Excellence for Aging Research CECAD, Cologne, Germany and the Babraham Institute, Cambridge, UK, have found that in mice, dietary restriction is strongly protective against age-related changes to our DNA. The results, published in Genome Biology, pave the way for understanding how age-related alterations to our epigenomes may have long-term consequences for gene expression and organ function, and how dietary restriction may prevent these changes.
We are more than our genomes – the order of the letters (ATGC), known as bases, in our DNA. On top of this sequence is another layer of control - our epigenome - which, by a process of adding or removing tags to our DNA and by altering DNA packaging inside our cell nuclei, controls which genes are on or off in different cell types. Our epigenome is known to be influenced by external factors including diet, making it a prime candidate linking dietary restriction and longevity.
The researchers found that restricting the food intake of mice to 40% of their counterparts resulted in a 30% increase in lifespan. They looked across the whole mouse genome to profile the epigenetic changes to DNA occurring in response to this dietary restriction and which might explain the lifespan extension. They found that dietary restriction controlled genes involved in establishing one type of epigenetic change – the tagging of specific DNA bases with a small chemical group (called DNA methylation). The result was that age-related changes to DNA methylation across the genome were substantially prevented by dietary restriction.
Oliver Hahn, PhD Student in the Partridge Group at the Max Planck Institute for the Biology of Ageing and lead author of the study said:
“Our research has identified physiologically meaningful epigenetic changes occurring during ageing. Dietary restriction partially protects against age-induced methylation changes whilst simultaneously instigating the reprogramming of lipid metabolism genes which seems to result in beneficial changes to which help our bodies function better”.
In addition to profiling the effects of dietary restriction on age-related changes to DNA methylation, the researchers also discovered a link between dietary restriction and the epigenetic repression of genes involved in lipid metabolism. Physiologically, the reprogramming of lipid metabolism caused by dietary restriction protected organisms against age-related increases of fat deposits in the liver and the development of hepatic insulin resistance, a feature of age-related type 2 diabetes.
Professor Wolf Reik, Head of the Epigenetics programme at the Babraham Institute, said:
“This work significantly advances our understanding of epigenetic regulation of ageing and dietary restriction by connecting the epigenome more directly with lipid changes associated with healthy ageing. Future work may reveal if dietary restriction leaves a long term epigenetic memory in the genome.”
This research was funded by the Max Planck Society, Bundesministerium für
Bildung und Forschung Grant SyBACol and European Research Council FP7 grant to researchers at the Max Planck Institute for Biology of Ageing, Cologne, Germany. Work at the Babraham Institute was supported by the BBSRC, Wellcome Trust, and the EpiGeneSys and BLUEPRINT EU Networks of Excellence.
Affiliated authors (in author order):
Thomas M. Stubbs, PhD student (Reik lab)
Gabriella Ficz, former postdoctoral research fellow (Reik lab)
Felix Krueger, Bioinformatician (Bioinformatics group)
Simon Andrews, Head of Bioinformatics
Qifeng Zhang, former Facility head, Lipidomics
Michael Wakelam, group leader and Institute Director
Wolf Reik, Head of Epigenetics programme and group leader at the Babraham Institute, and associate faculty at the Wellcome Trust Sanger Institute
Animal research statement:
As a publicly funded research institute, the Babraham Institute is committed to engagement and transparency in all aspects of its research. The use of animals in this study was performed in accordance with the recommendations and guideline of the Federation of the European Laboratory Animal Science Association (FELASA), with all protocols approved by the Landesamt für Natur, Umwelt und Verbraucherschutz, Nordrhein-Westfalen, Germany. The study used female F1 hybrid mice housed in groups of five in individually ventilated cages under specific-pathogen-free conditions.
Food uptake of control animals was measured weekly and dietary restriction was applied by feeding dietary restricted animals 40% less food. Adult-onset DR treatment was started at the age of 12 weeks in a stepwise manner, by reducing food amounts fed to DR animals by 10% each week until 40% reduction was reached. DR animals were fed once a day and all animals were checked daily to ensure their wellbeing.
At the ages of 5 and 27 months mice were euthanised for tissue sample collection.
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