Green, Cara L.

Low protein (LP) diets improve metabolic health in rodents and humans. In rodents, LP diets are typically implemented by replacing protein with carbohydrates like sucrose or cornstarch, keeping diets isocaloric. However, humans can choose from many different types of carbohydrate, and how dietary carbohydrate quality - the precise composition of the dietary sugars - impacts the response to dietary protein remains largely unexplored. Here, mice were fed control (21% protein) or LP (7% protein) diets with four different carbohydrate sources: sucrose, a 1:1 glucose/fructose mixture, glucose, or fructose. While LP diets improved metabolic health across all groups in male mice, carbohydrate quality also significantly altered specific health outcomes, with fructose-fed mice having the lowest body weight and adiposity of all control diets. In female mice, responses to LP diets were influenced by carbohydrate quality, with certain sugars inducing a stronger metabolic response to LP diets than previously seen. Finally, in female APP/PS1 mice, a model of Alzheimer's disease, we find that although LP diets reduce A-beta; plaque burden irrespective of carbohydrate type, dietary sugar type does influence spatial memory. Together, these results demonstrate that while dietary protein is a critical determinant of metabolic and neurological health, carbohydrate quality influences these outcomes in a sex-specific manner.

Abstract While the average human life span continues to increase, there is little evidence that this is leading to a contemporaneous increase in “healthy years” experienced by our aging population. Consequently, many scientists focus their research on understanding the process of aging and trialing interventions that can promote healthspan. The 2021 Midwest Aging Consortium consensus statement is to develop and further the understanding of aging and age-related disease using the wealth of expertise across universities in the Midwestern United States. This report summarizes the cutting-edge research covered in a virtual symposium held by a consortium of researchers in the Midwestern United States, spanning topics such as senescence biomarkers, serotonin-induced DNA protection, immune system development, multisystem impacts of aging, neural decline following severe infection, the unique transcriptional impact of calorie restriction of different fat depots, the pivotal role of fasting in calorie restriction, the impact of peroxisome dysfunction, and the influence of early life trauma on health. The symposium speakers presented data from studies conducted in a variety of common laboratory animals as well as less-common species, including Caenorhabditis elegans, Drosophila, mice, rhesus macaques, elephants, and humans. The consensus of the symposium speakers is that this consortium highlights the strength of aging research in the Midwestern United States as well as the benefits of a collaborative and diverse approach to geroscience.