Is Sex as a Biological Variable Still Being Ignored in Preclinical Aging Research?

Abstract

Five years ago, the National Institute of Health (NIH) introduced a mandate to revolutionize the way sex as a biological variable (SABV) is considered in NIH-funded preclinical research. Given the known effects of sex on aging physiology, pathology, treatment response, and the effectiveness of interventions it is particularly important that SABV be considered in basic biology of aging research. Five years after this mandate, a significant amount of published work funded by the National Institute on Aging (NIA) is still not including mice of both sexes and/or not considering sex differences or comparisons in preclinical studies. Here we review a cross-section of recently published NIA-funded research to determine adherence to this mandate. We discuss the state of the preclinical aging field in terms of SABV and suggest strategies for improving adherence to the NIH mandate. It is imperative that we consider SABV and include males and females in all aspects of aging biology research to improve health outcomes for all.

Keywords: Aging research; Female; Male; Preclinical; Sex.

Figure 1.

Results of an informal review of NIA-funded research in mice published from 2020 to 2021 and whether sex as a biological variable was considered. Five hundred and nine research articles were included from PubMed that reported NIH extramural research support, were published between January 1, 2020 and May 31, 2021, and included the search terms “NIA” and “mice”. (A) A pie graph indicating whether studies included male, female, both, or did not specify the sex of mice, and (B) of those that included both sexes, was data compared by sex. NIA = National Institute on Aging; NIH = National Institute of Health.

Figure 2.

Results of an informal review of NIA-funded research in mice published in subject specific journals dedicated to the biology of aging (Aging, Aging Cell, Experimental Gerontology, Geroscience, Journals of Gerontology Series A, and Neurobiology of Aging), from 2020 to 2021 and whether sex as a biological variable was considered. (A) A pie graph indicating whether studies included male, female, both, or did not specify the sex of mice, and (B) of those that included both sexes, was data compared by sex. NIA = National Institute on Aging.