Institute for Systems Biology, Seattle, WA, 98109, USA.
Department of Genetics, Paul F. Glenn Center for Biology of Aging Research at Harvard Medical School, Blavatnik Institute, Boston, MA, 02115, USA.
Biol Sex Differ. 2024 Oct 31;15(1):89. doi: 10.1186/s13293-024-00666-4.
Aging is a complex process that involves all tissues in an organism and shows sex dimorphism. While transcriptional changes in aging have been well characterized, the majority of studies have focused on a single sex and sex differences in gene expression in aging are poorly understood. In this study, we explore sex dimorphism in gene expression in aging mice across three tissues.
We collected gastrocnemius muscle, liver and white adipose tissue from young (6 months, n = 14) and old (24 months, n = 14) female and male C57BL/6NIA mice and performed RNA-seq. To investigate sex dimorphism in aging, we considered two levels of comparisons: (a) differentially expressed genes between females and males in the old age group and (b) comparisons between females and males across the aging process. We utilized differential expression analysis and gene feature selection to investigate candidate genes. Gene set enrichment analysis was performed to identify candidate molecular pathways. Furthermore, we performed a co-expression network analysis and chose the gene module(s) associated with aging independent of sex or tissue-type.
We identified both tissue-specific and tissue-independent genes associated with sex dimorphism in aged mice. Unique differentially expressed genes between old males and females across tissues were mainly enriched for pathways related to specific tissue function. We found similar results when exploring sex differences in the aging process, with the exception that in the liver genes enriched for lipid metabolism and digestive system were identified in both females and males. Combining enriched pathways across analyses, we identified amino acid metabolism, digestive system, and lipid metabolism as the core mechanisms of sex dimorphism in aging. Although the vast majority of age-related genes were sex and tissue specific, we identified 127 hub genes contributing to aging independent of sex and tissue that were enriched for the immune system and signal transduction.
There are clear sex differences in gene expression in aging across liver, muscle and white adipose. Core pathways, including amino acid metabolism, digestive system and lipid metabolism, contribute to sex differences in aging.
衰老是一个涉及生物体所有组织的复杂过程，并表现出性别二态性。虽然衰老过程中的转录变化已经得到很好的描述，但大多数研究都集中在单一性别上，对衰老过程中基因表达的性别差异了解甚少。在这项研究中，我们探索了三种组织中衰老小鼠的性别二态性。
我们收集了年轻（6 个月，n=14）和年老（24 个月，n=14）雌性和雄性 C57BL/6NIA 小鼠的腓肠肌、肝脏和白色脂肪组织，并进行了 RNA-seq。为了研究衰老过程中的性别二态性，我们考虑了两个比较水平：（a）老年组中雌性和雄性之间差异表达的基因，（b）整个衰老过程中雌性和雄性之间的比较。我们利用差异表达分析和基因特征选择来研究候选基因。进行了基因集富集分析以确定候选分子途径。此外，我们进行了共表达网络分析，并选择了与性别或组织类型无关的与衰老相关的基因模块。
我们确定了与老年小鼠性别二态性相关的组织特异性和组织非特异性基因。组织间老年雄性和雌性之间差异表达的独特基因主要富集与特定组织功能相关的途径。当我们探索衰老过程中的性别差异时，我们得到了类似的结果，除了肝脏中鉴定出的与脂质代谢和消化系统相关的基因在雌性和雄性中都存在。综合分析中富集的途径，我们确定了氨基酸代谢、消化系统和脂质代谢是衰老性别二态性的核心机制。尽管与衰老相关的大多数基因都是性别和组织特异性的，但我们鉴定出 127 个与性别和组织无关的衰老关键基因，这些基因富集于免疫系统和信号转导。
在肝脏、肌肉和白色脂肪中，衰老过程中的基因表达存在明显的性别差异。包括氨基酸代谢、消化系统和脂质代谢在内的核心途径有助于衰老过程中的性别差异。
