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

doi:10.1016/j.celrep.2018.10.070

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

Cell Rep. 2018 Nov 20;25(8):2234-2243.e6. doi: 10.1016/j.celrep.2018.10.070.

Affiliations

¹ 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.
² Charles Perkins Centre, The University of Sydney, Sydney, NSW 2006, Australia.
³ Charles Perkins Centre, The University of Sydney, Sydney, NSW 2006, Australia; School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Guangzhou 510275, China.
⁴ Charles Perkins Centre, The University of Sydney, Sydney, NSW 2006, Australia; School of Mathematics and Statistics, The University of Sydney, NSW 2006, Australia.
⁵ 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.
⁶ Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, MD 21224, USA.
⁷ Charles Perkins Centre, The University of Sydney, Sydney, NSW 2006, Australia. Electronic address: stephen.simpson@sydney.edu.au.
⁸ 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. Electronic address: david.lecouteur@sydney.edu.au.

Abstract

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.

Keywords: brain aging; calorie restriction; cardiometabolic health; cognitive function; hippocampus; protein restriction.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Aging / drug effects
Aging / physiology*
Animals
Behavior, Animal / drug effects
Biomarkers / metabolism
Body Composition / drug effects
Brain / drug effects
Brain / pathology
Brain / physiology*
Caloric Restriction
Cognition / drug effects
Dendritic Spines / drug effects
Dendritic Spines / metabolism
Diet, Protein-Restricted*
Dietary Carbohydrates / pharmacology*
Female
Gene Expression Regulation / drug effects
Heart / drug effects
Heart / physiology
Inflammation / pathology
Male
Memory / drug effects
Mice

Substances

Biomarkers
Dietary Carbohydrates

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

Authors

Affiliations

Abstract

Publication types

MeSH terms

Substances

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