Laboratory of Genetics and Genomics, National Institute on Aging Intramural Research Program, National Institutes of Health, Baltimore, MD 21224, USA.
Confocal Imaging Core Facility, National Institute on Aging Intramural Research Program, National Institutes of Health, Baltimore, MD 21224, USA.
Aging (Albany NY). 2024 Apr 17;16(8):6717-6730. doi: 10.18632/aging.205776.
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 are poorly 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 skin transcriptome of mutant Tabby male 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 male footpad skin, and 11 of them, including , and mRNAs, were found in the 'core secretory' category. Consistent with the changes in mRNA expression levels, immunohistology revealed that higher numbers of secretory cells from old SWGs express the transcription factor FOXC1, the protein product of mRNA. In sum, our study identified mRNAs enriched in SWGs, including those that encode core secretory proteins, and altered abundance of these mRNAs and proteins with aging in mouse SWGs.
皮肤表面的汗水蒸发是人体散热的主要机制。随着年龄的增长，汗腺的分泌能力下降，导致老年人不耐热，但导致这种下降的机制尚不清楚。我们研究了小鼠汗腺老化伴随的分子变化，通过汗液测试证实，与年轻小鼠相比，老年小鼠的活跃汗腺明显减少。我们首先通过 RNA 测序分析，比较了缺乏汗腺的突变 Tabby 雄性小鼠和野生型对照小鼠的皮肤转录组，从而确定了富含汗腺的 mRNA。这种比较揭示了 171 个在汗腺中富集的 mRNA，其中包括 47 个编码转录因子、离子通道、离子转运体和跨突触信号蛋白等“核心分泌”蛋白的 mRNA。在这些基因中，28 个富含汗腺的 mRNA 在老年雄性脚垫皮肤中的丰度发生了显著改变，其中包括 、 和 mRNA，它们都属于“核心分泌”类别。与 mRNA 表达水平的变化一致，免疫组织化学显示，来自老年汗腺的更多分泌细胞表达转录因子 FOXC1，即 mRNA 的蛋白产物。总之，我们的研究鉴定了富含汗腺的 mRNA，包括那些编码核心分泌蛋白的 mRNA，并且这些 mRNA 和蛋白的丰度随小鼠汗腺的老化而改变。
