The influence of a human macronutrient-matched diet on phenotypes in old mice

Abstract

Preclinical rodent models are essential research tools for improving understanding of physiological aging processes in humans. However, the translatability of findings obtained leveraging rodent models to humans is limited, likely due in part to differences in macronutrient composition of the diets. Here, we investigated the impact of a 3-month diet intervention in old male C57BL/6JN mice in which the macronutrient composition was aligned with that of a midlife/older adult in the United States, compared to a traditional rodent diet, and assessed various phenotypes that are typically altered with aging. Following the diet period, mice fed the human macronutrient-matched diet had greater quadricep and subcutaneous adipose and visceral adipose tissue masses compared to animals fed a traditional mouse diet. Frailty, assessed using a clinical frailty index, was lower, while grip strength was higher in mice fed the human-matched diet. Circulating metabolite and inflammatory cytokine profiles were altered in mice fed the human-matched diet. Notably, mortality rate (assessed in animals who died or were euthanized per veterinary recommendation before the pre-determined end of study euthanasia), tended to be lower in mice fed the human-matched diet. The present study underscores the importance of diet in rodent studies of aging, as differences in macronutrient composition can affect various physiological processes in old mice that are relevant to aging research.