Importance of integrating biological sex and age analyses in health research

Research findings in human, animal and cell populations may be influenced by biological sex and age. The traditional statistical approach to sex and/or age differences that are discovered in research data is to consider them as confounders that interfere with the ability to make accurate estimations and thus need to be controlled for. This article provides examples of how combining sexes or controlling for sex and/or age may lead to inaccurate findings and overlook important insights. Rather than treating these variables as confounding factors, they should be viewed as variables of importance to the research question. We contend that data should be analyzed according to sex/age as the primary analysis, while controlling for sex and age should be conducted as a secondary analysis. This topic is increasingly important as data are made publicly available and deep learning models/artificial intelligence are used to analyze large volumes of data. Mechanistic insights will continue to be lost if prompt action is not taken to report data according to sex and age and to analyze data by sex and age in health research.