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Developmental Biology - Obesity

Health in Old Age A Lifelong Affair

Reduced food intake early in life and eating less before old age begins - improves health in old mice...

Reduced food intake helps both animals and humans improve their health in old age — and can prolong life. But when do you have to change your diet to achieve this old age benefit?

Scientists from the Max Planck Institute for Biology of Ageing, Cologne, Germany and the Excellence Cluster for Ageing Research at the University of Cologne, the Babraham Institute in Cambridge, United Kingdom, and the University College London, London, UK (UCL) have now shown that mice only become healthier if they start food reduction early and eat less before entering old age. Their work appears in Nature Metabolism.
The scientists concluded that healthy eating behaviours must be established early in life to improve health and extend lifespan in old age.

Research gives a simple answer to the question "How can we stay fit and healthy in old age for as long as possible?" The answer: eat less and healthier. But when to start — and for how long must you manage to do this?

To investigate, Linda Partridge as director of the Max Planck Institute for Biology of Ageing, led an animal study which put young and old mice on diets with varying degrees of success.

Reduced Food Intake in Old Age Has No Beneficial Effect

Mice lived longer and were healthier in old age when given 40 percent less to eat after reaching adulthood, as compared to animals allowed to eat as much as they want. Dieting mice were fed food enriched with vitamins and minerals.
But, when food intake was first reduced in mice already seniors, researchers saw little or no affect on their life expectancy.

Mice allowed to eat as much as they like after a period of reduced food intake, had no long-term protection. Reduced food intake must therefore be implemented early and sustained until the end of life to have positive affects on health in old age.
"One should establish healthy behaviors early in life. Health in old age is a lifelong affair."

Linda Partridge PhD, 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 volume? Oliver Hahn, first author of the study and doctoral student in the Partridge department, investigated gene activity in different mouse organs seeking an explanation.
While gene activity in the liver quickly adapted in mice put on a restricted diet, scientists observed a 'memory effect' in fat tissue of older animals. Although the mice lost weight, gene activity in their fat tissue was similar to mice continuing to eat as much as they want.

Additionally, fat composition in old mice did not change as much as in young mice. This memory effect was mainly seen in mitochondria, the cell's power source, which plays an important role in ageing.
Usually, reduced food intake leads to increased formation of mitochondria in fatty tissue. But the study showed this is no longer the case when older mice are switched to lower calorie diets. Their inability to change at the genetic and metabolic levels may contribute to their shortened lifespan.

"The experimental power of integrating data about lipid metabolism and metabolic pathways with a tissue-specific understanding of gene expression in mice of different ages and diets, has allowed us to clearly demonstrate the importance of a nutritional memory in contributing to healthy ageing."

Michael Wakelam PhD, co-corresponding author and Director of the Babraham Institute.

Dietary restriction (DR) during adulthood can greatly extend lifespan and improve metabolic health in diverse species. However, whether DR in mammals is still effective when applied for the first time at old age remains elusive. Here, we report results of a late-life DR-switch experiment using 800 mice. Female mice aged 24 months were switched from an ad libitum (AL) diet to DR or vice versa. Strikingly, the switch from DR to AL acutely increases mortality, whereas the switch from AL to DR causes only a weak and gradual increase in survival, suggesting the body has a memory of earlier nutrition. RNA sequencing in liver and brown and white adipose tissue (BAT and WAT, respectively) demonstrates a largely refractory transcriptional and metabolic response in fat tissue to DR after an AL diet, particularly in WAT, and a proinflammatory signature in aged preadipocytes, which is prevented by chronic DR feeding. Our results provide evidence for a ‘nutritional memory’ as a limiting factor for DR-induced longevity and metabolic remodelling of WAT in mammals.

Oliver Hahn, Lisa F. Drews, An Nguyen, Takashi Tatsuta, Lisonia Gkioni, Oliver Hendrich, Qifeng Zhang, Thomas Langer, Scott Pletcher, Michael J. O. Wakelam, Andreas Beyer, Sebastian Grönke and Linda Partridge.

The authors thank R. Weindruch, J. Nelson, R. Miller, C. Selman, D. Withers and F. Kiefer for their advice on the mouse dietary restriction protocol and Dietmar Vestweber and the Max Planck Institute for Molecular Biomedicine, Münster, Germany, for kindly allowing us to conduct our studies at their facilities. We further thank I. Gravemeier, U. Hill, J. Matutat, A. Mesaros and B. Neuhaus for assistance with mouse work. We thank T. Wyss-Coray and the Tabula Muris consortium for kindly granting access to their single-cell transcriptome atlas, and for advice and supervision during the corresponding analysis. We acknowledge funding from the Max Planck Society, Bundesministerium für Bildung und Forschung Grant SyBACol 0315893A-B (to AB and LP) and the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007-2013)/ERC grant agreement number 268739 to L.P. M.J.O.W., A.N. and Q.Z. thank the BBSRC (BB/P013384/1) and the MRC (MR/M004821/1) for financial support.

The authors declare no competing interests.

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Nov 8 2019   Fetal Timeline   Maternal Timeline   News  

Nutritional Memory Counters Affects of Diet Restriction in Older Mice

Scientists conclude that healthy behaviour must be established early in life to improve
health in old age and extend lifespan. IMAGE CREDIT Public Domain.

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