Researchers here show that declining expression of the aquaporin AQP1 influences the age-related increase in cellular senescence in tendon stem cells and progenitor cells. Since the more general acceptance in the research community of senescent cell accumulation as an important cause of degenerative aging, there has been an increased interest in deeper investigations of the biochemistry of cellular senescence. It isn't clear that preventing cells from becoming senescent is always going to be beneficial, however. Does the method of prevention work by reducing cell damage and dysfunction that provokes senescence, which is a good thing, or does it work by holding back senescence in damaged and dysfunctional cells? That latter option may cause more problems than it solves.
Previous studies have demonstrated that tendon aging is closely associated with the functional changes of tendon stem/progenitor cells (TSPCs). TSPCs express classical stem cell markers and typical tendon-lineage genes. Studies have demonstrated the vital role of TSPCs in tendon repair, regeneration, and homeostasis maintaining. However, TSPCs premature entry into senescence during tendon aging, senescent TSPCs exhibit reduced self-renewal, migration, and tenogenic differentiation capacity compared with young cells, and these age-related changes in TSPCs would impair tendon healing and regeneration capacity.
Aquaporins (AQPs) are a family of small water-transporting membrane proteins. Previous studies also indicated that AQP1 is involved in tissue aging. In aged skin tissue, AQP1 level was decreased, which might be correlated with aging-related skin dryness. In addition, recent studies have indicated that AQP1 is also involved in the regulation of stem cells. Although studies have indicated the important role of AQP1 in tissue aging and regulation of stem cell, there were no studies focused on the role of AQP1 in TSPCs senescence.
In the present study, we investigated the AQP1 expression profile of TSPCs isolated from rats at different ages. We demonstrated that AQP1 expression declines with age in TSPCs, and AQP1 plays a vital role in TSPCs senescence. Decreased AQP1 was associated with activation of JAK-STAT signaling pathways in aged TSPCs. Furthermore, overexpression of AQP1 restored the age-related reduction of self-renewal, migration, and tenogenic differentiation in TSPCs. Our results collectively indicated that AQP1 could be an ideal target for antagonizing tendon aging.