Protocol for the systematic review of age and sex in preclinical models of age-correlated diseases [version 2; peer review: 1 approved with reservations]

The translation of animal-based biomedical research into clinical research is often inadequate. Maximizing translation should be central to animal research on human diseases, guiding researchers in study design and animal model selection. However, practical considerations often drive the choice of animal model, which may not always reflect key patient characteristics, such as sex and age, impacting the disease's course. Despite diseases affecting both sexes, researchers frequently use male mice. To address this imbalance, journals and funding agencies have begun questioning the sex of animals used in studies and issued new guidelines. Conversely, the age of rodents is rarely discussed, even though many diseases primarily affect older patients. Young mice are commonly used, even in studies of diseases affecting older adults. Systematic comparisons between the age of rodents used and the age of patients in clinical trials are lacking. In this review, we systematically analyze the age and sex of mice used to model the five leading causes of global disability-adjusted life-years over the age of 75. We compare the results with the age and sex of patients in clinical trials focusing on Alzheimer's disease, stroke, type 2 diabetes mellitus, ischemic heart disease, and chronic obstructive pulmonary disease. We also analyze whether the age of the mice used has changed over the past decade. By systematically assessing the age and sex of the mice, we aim to initiate a discussion on the appropriate choice of animal model to improve the translatability of research results.