Comparing the Effects of Low-Protein and High-Carbohydrate Diets and Caloric Restriction on Brain Aging in Mice

Devin Wahl; Samantha M. Solon-Biet; Qiao-Ping Wang; Jibran A. Wali; Tamara Pulpitel; Ximonie Clark; David Raubenheimer; Alistair M. Senior; David A. Sinclair; Gregory J. Cooney; Rafael de Cabo; Victoria C. Cogger; Stephen J. Simpson; David G. Le Couteur

Cell Reports (Nov 2018)

Comparing the Effects of Low-Protein and High-Carbohydrate Diets and Caloric Restriction on Brain Aging in Mice

Devin Wahl,
Samantha M. Solon-Biet,
Qiao-Ping Wang,
Jibran A. Wali,
Tamara Pulpitel,
Ximonie Clark,
David Raubenheimer,
Alistair M. Senior,
David A. Sinclair,
Gregory J. Cooney,
Rafael de Cabo,
Victoria C. Cogger,
Stephen J. Simpson,
David G. Le Couteur

Affiliations

Devin Wahl: Charles Perkins Centre, The University of Sydney, Sydney, NSW 2006, Australia; Aging and Alzheimers Institute, ANZAC Research Institute, Centre for Education and Research on Ageing, Concord, NSW 2139, Australia
Samantha M. Solon-Biet: Charles Perkins Centre, The University of Sydney, Sydney, NSW 2006, Australia
Qiao-Ping Wang: Charles Perkins Centre, The University of Sydney, Sydney, NSW 2006, Australia; School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Guangzhou 510275, China
Jibran A. Wali: Charles Perkins Centre, The University of Sydney, Sydney, NSW 2006, Australia
Tamara Pulpitel: Charles Perkins Centre, The University of Sydney, Sydney, NSW 2006, Australia
Ximonie Clark: Charles Perkins Centre, The University of Sydney, Sydney, NSW 2006, Australia
David Raubenheimer: Charles Perkins Centre, The University of Sydney, Sydney, NSW 2006, Australia
Alistair M. Senior: Charles Perkins Centre, The University of Sydney, Sydney, NSW 2006, Australia; School of Mathematics and Statistics, The University of Sydney, NSW 2006, Australia
David A. Sinclair: Department of Genetics, Paul F. Glenn Center for the Biology of Aging, Harvard Medical School, Boston, MA 02115, USA; Department of Pharmacology, School of Medical Sciences, The University of New South Wales, Sydney, NSW 2052, Australia
Gregory J. Cooney: Charles Perkins Centre, The University of Sydney, Sydney, NSW 2006, Australia
Rafael de Cabo: Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, MD 21224, USA
Victoria C. Cogger: Charles Perkins Centre, The University of Sydney, Sydney, NSW 2006, Australia; Aging and Alzheimers Institute, ANZAC Research Institute, Centre for Education and Research on Ageing, Concord, NSW 2139, Australia
Stephen J. Simpson: Charles Perkins Centre, The University of Sydney, Sydney, NSW 2006, Australia; Corresponding author
David G. Le Couteur: Charles Perkins Centre, The University of Sydney, Sydney, NSW 2006, Australia; Aging and Alzheimers Institute, ANZAC Research Institute, Centre for Education and Research on Ageing, Concord, NSW 2139, Australia; Corresponding author

Journal volume & issue: Vol. 25, no. 8
pp. 2234 – 2243.e6

Abstract

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Summary: Calorie restriction (CR) increases lifespan and improves brain health in mice. Ad libitum low-protein, high-carbohydrate (LPHC) diets also extend lifespan, but it is not known whether they are beneficial for brain health. We compared hippocampus biology and memory in mice subjected to 20% CR or provided ad libitum access to one of three LPHC diets or to a control diet. Patterns of RNA expression in the hippocampus of 15-month-old mice were similar between mice fed CR and LPHC diets when we looked at genes associated with longevity, cytokines, and dendrite morphogenesis. Nutrient-sensing proteins, including SIRT1, mTOR, and PGC1α, were also influenced by diet; however, the effects varied by sex. CR and LPHC diets were associated with increased dendritic spines in dentate gyrus neurons. Mice fed CR and LPHC diets had modest improvements in the Barnes maze and novel object recognition. LPHC diets recapitulate some of the benefits of CR on brain aging. : Calorie restriction (CR) and ad libitum low-protein, high-carbohydrate (LPHC) diets improve cardiometabolic health in mice. Wahl et al. show that, like healthspan, CR and LPHC diets positively affect hippocampus biology in mice by influencing hippocampus gene expression, nutrient-sensing pathways, dendritic morphology, and cognition. Keywords: calorie restriction, cognitive function, protein restriction, brain aging, hippocampus, cardiometabolic health

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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