Characterizing Age-Related Changes in Sweat Gland Biochemistry
The progressive dysfunction of sweat glands in the skin is probably not high on the list of items that people think about in the context of degenerative aging, at least not until they experience it. A reduced capacity of sweat glands leads to heat intolerance, and it is one of the contributing causes of the raised mortality rate among the elderly in heat waves. Here, researchers examine some of the biochemistry of sweat gland cells in aging mice. They focus in on a number of proteins that may turn out to be viable targets for drugs to force sweat glands in aged skin back to a more youthful degree of function. It is a long road from fundamental investigations of this sort to that outcome, however.
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 messenger RNAs (mRNAs) by comparing the skin transcriptome of Eda 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 Foxa1, Best2, Chrm3, and Foxc1 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 Foxc1 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.