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Ales demonstrated an increased animal-to-animal variance with aging that was not evident in females. Previously increased cell-to-cell variability of gene expression in cardiomyocytes [45] with aging has been reported, as well as animal-to-animal increases in gene PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/27486068 expression variance in a variety of tissues in males [46, 47, 109]. We observe that males steadily increase in variance across the lifespan while females do not, ultimately resulting in a higher level of inter-animal variance in old age in males as compared to females. The only report we are aware of XAV-939 web examining males and females also found that inter-animal variance increased only in males [109]. The functional implications of this difference are not clear, but this may be a result of underlying epigenetic changes [110]. Confirmation studies across multiple tissues and with higher sample numbers are needed to explore this intrinsic variability with aging in males. Lastly, for both the sex divergences in gene expression and the increased variance in gene expression only observed in males, future studies will need to dissect the causes of these differences at the level of development, direct action of gonadal hormones, or sex chromosomes [93] and whether these age-related alterations are associated with cognitive impairment [111].Conclusions The results presented here demonstrate that aged females experience a distinct difference in brain aging when compared to age-matched males, suggesting females undergo a higher level of microglial activation with age. These data have significant implications on theMangold et al. Journal of Neuroinflammation (2017) 14:Page 17 ofmolecular mechanisms underlying brain aging, and the development of neurodegenerative disease in males and females, highlighting the importance of studying both sexes in geroscience research. This study did not seek to mechanistically explain sexually divergent responses with aging. Future studies, preferably from isolated cell types or single cells, are needed to address the origin of these sex-specific responses in gene expression. Additionally, examinations of the functional implications of sexually divergent aging responses are needed. Nonetheless, these data provide a compelling rationale for the inclusion of both female and male rodents in basic aging research and offer important new avenues for future investigation.Competing interests The authors declare that they have no competing interests.Publisher’s NoteSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Author details 1 Department of Biochemistry and Molecular Biology, Pennsylvania State University, State College, PA, USA. 2Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. 3Reynolds Oklahoma Center on Aging Nathan Shock Center of Excellence in the Biology of Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. 4Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. 5Genome Sciences Facility, Pennsylvania State University College of Medicine, Hershey, PA, USA. 6 Division of Neuroscience, Oregon National Primate Research Center, Beaverton, Oregon, USA. 7Department of Geriatric Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, USA. 8SLY-BRC 1370, 975 NE 10th St, Oklahoma City, OK 73104, USA. Received: 1 September 2016 Accepted: 13 JulyAdditional filesA.

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Author: haoyuan2014