Characterization of age-associated gene expression changes in mouse sweat glands [FP_YO]

Evaporation of sweat on the skin surface is the major mechanism for dissipating heat in humans. The secretory capacity of sweat glands (SWGs) declines during aging, leading to heat intolerance in the elderly, but the mechanisms responsible for this decline remain incompletely understood. We investigated the molecular changes accompanying SWG aging in mice, where sweat tests confirmed a significant reduction of active SWGs in old mice relative to young mice. We first identified SWG-enriched mRNAs by comparing the transcriptome of Eda mutant Tabby mice, which lack SWGs, with that of wild-type control mice by RNA-sequencing analysis. This comparison revealed 171 mRNAs enriched in SWGs, including 47 mRNAs encoding core secretory proteins such as transcription factors, ion channels, ion transporters, and trans-synaptic signaling proteins. Among these, 28 SWG-enriched mRNAs showed significantly altered abundance in the aged footpad skin, and 11 of them, including Foxa1, Best2, Chrm3, and Foxc1 mRNAs belonged to the core secretory category. Consistent with the changes in mRNA expression, immunohistology revealed that higher numbers of secretory cells from old SWGs express FOXC1 protein, the product of Foxc1 mRNA. In sum, our study identified mRNAs enriched in SWGs, including those that encode core secretory proteins, and changes in these mRNAs and proteins with SWG aging in mice.皮肤表面汗液的蒸发是人体散热的核心机制。汗腺（sweat glands, SWGs）的分泌功能随衰老逐渐衰退，进而引发老年人耐热能力受损的问题，但该衰退的具体分子机制仍未完全阐明。本研究以小鼠为模型，探究了汗腺衰老伴随的分子变化：汗液检测实验证实，与年轻小鼠相比，老年小鼠体内的功能性汗腺数量显著减少。我们首先通过RNA测序（RNA-sequencing）分析，对比了缺乏汗腺的Eda突变型Tabby小鼠与野生型对照小鼠的转录组，由此鉴定出171个汗腺富集的mRNA，其中包含47个编码核心分泌蛋白的mRNA，涉及转录因子、离子通道、离子转运蛋白及跨突触信号蛋白等类别。在上述汗腺富集的mRNA中，有28个在老年小鼠足垫皮肤中的表达丰度发生了显著改变，其中11个属于核心分泌蛋白编码基因，包括Foxa1、Best2、Chrm3与Foxc1等mRNA。与mRNA的表达变化相一致，免疫组化实验显示，老年汗腺的分泌细胞中FOXC1蛋白（Foxc1 mRNA的编码产物）的表达水平更高。综上，本研究鉴定出了汗腺富集的mRNA（包括编码核心分泌蛋白的相关基因），并揭示了小鼠汗腺衰老过程中这些mRNA与对应蛋白的表达变化。