Protein restriction slows the development and progression of pathology in a mouse model of Alzheimer’s disease
Year: 2024
Type: article
Abstract: Dietary protein is a critical regulator of metabolic health and aging. Low protein diets are associated with healthy aging in humans, and many independent groups of researchers have shown that dietary protein restriction (PR) extends the lifespan and healthspan of mice. Here, we examined the effect of PR on metabolic health and the development and progression of Alzheimer's disease (AD) in the 3xTg mouse model of AD. We found that PR has metabolic benefits for 3xTg mice and non-transgenic controls of both sexes, promoting leanness and glycemic control in 3xTg mice and rescuing the glucose intolerance of 3xTg females. We found that PR induces sex-specific alterations in circulating metabolites and in the brain metabolome and lipidome, downregulating sphingolipid subclasses including ceramides, glucosylceramides, and sphingomyelins in 3xTg females. Consumption of a PR diet starting at 6 months of age reduced AD pathology in conjunction with reduced mTORC1 activity, increased autophagy, and had cognitive benefits for 3xTg mice. Finally, PR improved the survival of 3xTg mice. Our results demonstrate that PR slows the progression of AD at molecular and pathological levels, preserves cognition in this mouse model of AD, and suggests that PR or pharmaceutical interventions that mimic the effects of this diet may hold promise as a treatment for AD.
Source: Nature Communications
Authors: Reji Babygirija, Michelle M. Sonsalla, Jericha Mill, Isabella James, Jessica H. Han, Cara L. Green, Mariah F. Calubag, Gina Wade, Anna Tobon, John Michael, Michaela M. Trautman, Ryan Matoska, Chung-Yang Yeh, Isaac Grunow, Heidi H. Pak, Michael J. Rigby, Dominique A. Baldwin, Natalie M. Niemi, John M. Denu, Luigi Puglielli, Judith Simcox, Dudley W. Lamming
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $6,790
Funders: Howard Hughes Medical Institute, U.S. Department of Health and Human Services, U.S. Department of Veterans Affairs, Alzheimer's Association, Glenn Foundation for Medical Research, Fondation pour la Recherche Médicale, National Institutes of Health, National Institute on Aging, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: Regulation of cellular senescence and metabolic health by dietary protein, G1581258015, G1958926423, G2276492847, G2305088843, G2337220457, G2375471656, G2388130288, G2401706436, G2739848184, G2795387801, G2887534901, G2958551245, G2989705085, G3030709050, G307440276, G3330331223, G3731043192, G3930223526, Dietary Interventions in Alzheimer’s Disease, G406957865, G4232768455, Safer mTOR inhibition for human geroprotection, G42610423, G4755141327, Comparative analysis of geroprotective interventions in established and novel mouse models of Alzheimer's disease, G5105223188, G5284041279, University of Wisconsin Building Interdisciplinary Research Careers in Women's Health (BIRCWH) Scholars Program, G5487742219, G5581438442, Translation analysis of a novel intervention for diet-induced obesity, The regulation of health and longevity by branched-chain amino acids, G5872938734, The regulation of cancer and aging by methionine, Discovery and characterization of a novel acylcarnitine transporter in brown adipocytes, G6460484544, G6555710345, G6733044160, G6882896998, G6956534337, G711410796, G7191816419, G7667824514, G7727581783, G7770927085, The regulation of health and longevity by branched-chain amino acids, G8464745751, G866501853, Dietary regulation of the hepatic epigenome, G880996693, G8906462684, G9000025623, G9000027241, G9000112001, G9000115444, G9000131312, G9000237573, G9000300278, G9000355804, ATase1 and ATase2, proteostasis, and neurological diseases, Dynamics and molecular mechanisms linking metabolism and the epigenome, Delineating phosphorylation-mediated regulation of mitochondrial function, The Role of Prolonged Fasting in the Effects of Calorie Restriction on AD, G938344928
OpenAlex ID: W4399766693