Short-term periodic restricted feeding elicits metabolome-microbiome signatures with sex dimorphic persistence in primate intervention

Hagai Yanai, Bongsoo Park, Hyunwook Koh, Hyo Jung Jang, Kelli L. Vaughan, Mayuri Tanaka-Yano, Miguel Aon, Madison Blanton, Ilhem Messaoudi, Alberto Diaz-Ruiz, Julie A. Mattison and Isabel Beerman ()
Additional contact information
Hagai Yanai: National Institute on Aging, NIH
Bongsoo Park: National Institute on Aging, NIH
Hyunwook Koh: The State University of New York, Korea (SUNY Korea)
Hyo Jung Jang: The State University of New York, Korea (SUNY Korea)
Kelli L. Vaughan: National Institute on Aging, NIH
Mayuri Tanaka-Yano: National Institute on Aging, NIH
Miguel Aon: National Institute on Aging, NIH
Madison Blanton: University of Kentucky
Ilhem Messaoudi: University of Kentucky
Alberto Diaz-Ruiz: Precision Nutrition and Aging Program, Institute IMDEA Food (CEI UAM+CSIC)
Julie A. Mattison: National Institute on Aging, NIH
Isabel Beerman: National Institute on Aging, NIH

Nature Communications, 2024, vol. 15, issue 1, 1-11

Abstract: Abstract Dietary restriction has shown benefits in physiological, metabolic, and molecular signatures associated with aging but is a difficult lifestyle to maintain for most individuals. In mice, a less restrictive diet that allows for cyclical periods of reduced calories mitigates aging phenotypes, yet the effects of such an intervention in a genetically heterogenous, higher-order mammal has not been examined. Here, using middle-aged rhesus macaques matched for age and sex, we show that a regimen of 4 days of low-calorie intake followed by 10 days of ad libitum feeding (4:10 diet) performed in repeating cycles over 12 weeks led to significant loss of weight and fat percentage, despite the free access to food for most of the study duration. We show the 4-day restriction period is sufficient to drive alterations to the serum metabolome characterized by substantial differences in lipid classes. These phenotypes were paralleled by changes in the gut microbiome of restricted monkeys that highlight the involvement of a microbiome-metabolome axis. This regimen shows promising phenotypes, with some sex-dimorphic responses, including residual memory of the diet. As many calorie restriction interventions are difficult to sustain, we propose that this short-term diet may be easier to adhere to and have benefits directly relevant to human aging.

Date: 2024
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DOI: 10.1038/s41467-024-45359-z

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