Research Press Release

A nutritional memory effect counteracts the benefits of dietary restriction in old mice

Nature Metabolism

October 22, 2019

Switching to a dietary-restricted (DR) diet later in life does not make mice live longer, a study published in Nature Metabolism reports. The findings suggest that the late adoption of a healthful diet cannot undo the damage caused by a previously unrestricted diet. Whether these findings translate to humans remains to be seen.

Lifelong dietary restriction (20 - 40% reduction of normal calorie intake) has well-documented health benefits and is known to extend the lifespan of many animals. However, whether dietary restriction still works when initiated relatively late in life is unclear.

Linda Partridge and colleagues investigated the effects of dietary restriction in 800, 24-month-old female mice. Some mice were switched from an unrestricted, ad libitum diet to a DR diet or vice versa. Mice switched from a DR to an unrestricted diet quickly became unhealthy and died earlier than those that remained on a DR diet. However, even though they were healthier, the mice switched from an unrestricted to a DR diet did not live longer than mice that remained on an unrestricted diet. The authors found that the molecular response to a DR diet was different in the fat tissues of the mice previously given unrestricted access to food for most of their life. The authors propose a ‘nutritional memory effect’ in fat tissue that suppresses the beneficial effects of dietary restriction on health and survival.

The study provides a detailed investigation into the potential benefits of late-onset DR in mice. However, the authors highlight that whether the molecular mechanisms underlying the proposed nutritional memory effect also apply to humans remains to be established.

doi:10.1038/s42255-019-0121-0

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