Summary: According to researchers, dietary restrictions can lead to alterations in lipid metabolism, which helps to increase lifespan in mice.
Source: Max Planck Institute.
In mice, dietary restrictions can lead to changes in lipid metabolism, thus increasing the animals’ lifespans.
Reduced food consumption extends the lifespan of many organisms, including primates. The biology behind how this is achieved, however, is not yet fully understood. Researchers at the Max Planck Institute for Biology of Ageing and the Cluster of Excellence for Aging Research CECAD, Cologne, Germany, as well as the Babraham Institute in Cambridge have now found that in mice, dietary restriction triggers epigenetic changes in the DNAGenes, for example, which are important for the lipid metabolism, are switched off. Dietary restriction can thus prevent the consequences of age-related changes in the so-called epigemome.
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 40percent of their counterparts resulted in a 30 percent 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.
Wolf Reik, Head of the Epigenetics programme at the Babraham Institute, explained: “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.”
Source: Maren Berghoff – Max Planck Institute
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Original Research: Full open access research for “Dietary restriction protects from age-associated DNA methylation and induces epigenetic reprogramming of lipid metabolism” by Oliver Hahn, Sebastian Grönke, Thomas M. Stubbs, Gabriella Ficz, Oliver Hendrich, Felix Krueger, Simon Andrews, Qifeng Zhang, Michael J. Wakelam, Andreas Beyer, Wolf Reik and Linda Partridge in Genome Biology. Published online March 28 2017 doi:10.1186/s13059-017-1187-1
Dietary restriction protects from age-associated DNA methylation and induces epigenetic reprogramming of lipid metabolism
Dietary restriction (DR), a reduction in food intake without malnutrition, increases most aspects of health during aging and extends lifespan in diverse species, including rodents. However, the mechanisms by which DR interacts with the aging process to improve health in old age are poorly understood. DNA methylation could play an important role in mediating the effects of DR because it is sensitive to the effects of nutrition and can affect gene expression memory over time.
Here, we profile genome-wide changes in DNA methylation, gene expression and lipidomics in response to DR and aging in female mouse liver. DR is generally strongly protective against age-related changes in DNA methylation. During aging with DR, DNA methylation becomes targeted to gene bodies and is associated with reduced gene expression, particularly of genes involved in lipid metabolism. The lipid profile of the livers of DR mice is correspondingly shifted towards lowered triglyceride content and shorter chain length of triglyceride-associated fatty acids, and these effects become more pronounced with age.
Our results indicate that DR remodels genome-wide patterns of DNA methylation so that age-related changes are profoundly delayed, while changes at loci involved in lipid metabolism affect gene expression and the resulting lipid profile.
“Dietary restriction protects from age-associated DNA methylation and induces epigenetic reprogramming of lipid metabolism” by Oliver Hahn, Sebastian Grönke, Thomas M. Stubbs, Gabriella Ficz, Oliver Hendrich, Felix Krueger, Simon Andrews, Qifeng Zhang, Michael J. Wakelam, Andreas Beyer, Wolf Reik and Linda Partridge in Genome Biology. Published online March 28 2017 doi:10.1186/s13059-017-1187-1