Center for Precision Medicine, Wake Forest University Health Sciences, Winston-Salem, NC, USA; Section on Molecular Medicine, Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA; Section on Comparative Medicine, Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, NC, USA; Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, TX, USA.
Center for Precision Medicine, Wake Forest University Health Sciences, Winston-Salem, NC, USA; Section on Molecular Medicine, Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
Neurobiol Aging. 2023 Dec;132:109-119. doi: 10.1016/j.neurobiolaging.2023.08.009. Epub 2023 Aug 29.
The prefrontal cortex (PFC) has been implicated as a key brain region responsible for age-related cognitive decline. Little is known about aging-related molecular changes in PFC that may mediate these effects. To date, no studies have used untargeted discovery methods with integrated analyses to determine PFC molecular changes in healthy female primates. We quantified PFC changes associated with healthy aging in female baboons by integrating multiple omics data types (transcriptomics, proteomics, metabolomics) from samples across the adult age span. Our integrated omics approach using unbiased weighted gene co-expression network analysis to integrate data and treat age as a continuous variable, revealed highly interconnected known and novel pathways associated with PFC aging. We found Gamma-aminobutyric acid (GABA) tissue content associated with these signaling pathways, providing 1 potential biomarker to assess PFC changes with age. These highly coordinated pathway changes during aging may represent early steps for aging-related decline in PFC functions, such as learning and memory, and provide potential biomarkers to assess cognitive status in humans.
前额叶皮层（PFC）被认为是负责与年龄相关的认知能力下降的关键大脑区域。关于 PFC 中与衰老相关的分子变化，这些变化可能介导这些影响，但知之甚少。迄今为止，没有研究使用具有综合分析的非靶向发现方法来确定健康雌性灵长类动物的 PFC 分子变化。我们通过整合成年期跨度内的多个组学数据类型（转录组学、蛋白质组学、代谢组学），来定量评估雌性狒狒 PFC 与健康衰老相关的变化。我们使用无偏加权基因共表达网络分析的综合组学方法来整合数据并将年龄视为连续变量，揭示了与 PFC 衰老相关的高度互联的已知和新的途径。我们发现与这些信号通路相关的γ-氨基丁酸（GABA）组织含量，为评估 PFC 随年龄变化提供了 1 种潜在的生物标志物。这些在衰老过程中高度协调的途径变化可能代表了与 PFC 功能相关的衰老相关下降的早期步骤，例如学习和记忆，并为评估人类认知状态提供了潜在的生物标志物。
