Health in old age is a lifelong affair

Key points

• Research explored the impact of the timing of a switch to dietary restriction on health and lifespan in mice.
• The research published in Nature Metabolism shows that, in mice, the gain in lifespan is dependent on early adoption.
• Initiating dietary restriction in older mice does not deliver the same benefits, explained by evidence of a nutritional memory effect in the body.

Reduced food intake helps both animals and humans to improve health in old age and can prolong life. But when do you have to change your diet to achieve this benefit in old age? To investigate this, researchers led by Linda Partridge, Director at the Max Planck Institute for Biology of Ageing, have put young and old mice on a diet - with varying degrees of success. The study, published in the scientific journal Nature Metabolism, demonstrates that mice only become healthier if they start food reduction early and eat less before entering old age. The scientists, from the Max Planck Institute for Biology of Ageing, the Excellence Cluster for Ageing Research at the University of Cologne, the Babraham Institute in Cambridge, and UCL, conclude that healthy behaviour must be established earlier in life in order to improve health in old age and extend lifespan.
 
Reduced food intake in old age has no beneficial effect
In the study, mice lived longer and were healthier in old age if they were given 40 percent less to eat after reaching adulthood than animals who were allowed to eat as much as they wanted. The dieting mice were fed with food enriched with vitamins and minerals to prevent malnutrition. If food intake was first reduced in mice when they were already seniors, the researchers observed little or no effect on the life expectancy of the mice. On the other hand, when mice were allowed to eat as much as they liked after a period of reduced food intake, they had no long-term protection, so reduced food intake had to be sustained for mice to reap the benefits. In mice at least, the results suggest that reduced food intake must be implemented early and be sustained until the end of life to have positive effects on health in old age.
 
"One should establish healthy behaviours early in life. It may not be as good for your health to change your diet later in life. Health in old age is a lifelong affair", explains Linda Partridge from the Max Planck Institute for the Biology of Ageing and UCL.
 
Memory effect in fat tissue
But why do older mice no longer react to the change in diet? Oliver Hahn, first author of the study and a doctoral student in the Partridge department, investigated gene activity in different organs. While the gene activity in the liver quickly adapted when mice were transferred to a restricted diet, the scientists observed a ‘memory effect’ in the fat tissue of older animals. Although the mice lost weight, the activity of the genes in the fat tissue was similar to that of the mice that continued to eat as much as they wanted. In addition, the fat composition in old mice did not change as much as in young mice. This memory effect mainly affected mitochondria, the cells’ power houses, which play an important role in the ageing process. Usually, reduced food intake leads to increased formation of mitochondria in fatty tissue. But the study showed that this is no longer the case when older mice are switched to a lower calorie diet. This inability to change at the genetic and metabolic levels may contribute to the shortened lifespan of these animals.
 
Michael Wakelam, co-corresponding author and Director of the Babraham Institute commented, “The experimental power of integrating data about lipid metabolism and metabolic pathways with tissue-specific understanding of gene expression in mice of different ages and diets has allowed us to demonstrate clearly the importance of a nutritional memory in contributing to healthy ageing.”
 

Notes to Editors

Publication reference
Hahn et al. A nutritional memory effect counteracts the benefits of dietary restriction in old mice. Nature Metabolism

Contacts
Dr Maren Berghoff, PR Executive, Max Planck Institute for Biology of Ageing, Maren.berghoff@age.mpg.de , +49 221 37970207
 
Dr Louisa Wood, Babraham Institute Communications Manager, louisa.wood@babraham.ac.uk, 01223 496230
 
Image
Mice become healthier through a change in diet if they start early in life and are fed this way into old age. Image shows a mouse that had unrestricted access to food. Image credit: Lisa F. Drews for Max Planck Institute for Biology of Ageing.

Affiliated authors (in author order)
An Nguyen, researcher, Wakelam group
Qifeng Zhang, previous Head of the Lipidomics facility
Michael Wakelam, Institute Director, Head of the Lipidomics facility and group leader in the Institute's Signalling research programme. 

Funding
The researchers acknowledge funding from the Max Planck Society, Bundesministerium für Bildung und Forschung Grant and the European Research Council under the European Union’s Seventh Framework Programme. The Babraham Institute's contribution to the project was supported by the BBSRC and the MRC.

About the Max Planck Institute for Biology of Ageing
The Max Planck Institute for Biology of Ageing investigates the natural ageing process with the long-term goal to pave the way towards increasing health during ageing in humans. It is an institute within the Max Planck Society, which is one of Germany’s most successful research organisations. Since its foundation in 2008 the institute is an integral part of a life science cluster in Cologne that pursue ageing research.
www.age.mpg.de
 
About the Babraham Institute
The Babraham Institute undertakes world-class life sciences research to generate new knowledge of biological mechanisms underpinning ageing, development and the maintenance of health. Our research focuses on cellular signalling, gene regulation and the impact of epigenetic regulation at different stages of life. By determining how the body reacts to dietary and environmental stimuli and manages microbial and viral interactions, we aim to improve wellbeing and support healthier ageing. The Institute is strategically funded by the Biotechnology and Biological Sciences Research Council (BBSRC), part of UK Research and Innovation, through an Institute Core Capability Grant and also receives funding from other UK research councils, charitable foundations, the EU and medical charities.
www.babraham.ac.uk
 
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