Aquaporins in the Senescence of Tendons

Senescence, a hallmark of aging, is a state in which cells stop dividing. Once a cell is senescent, it secretes signals called the Senescence Associated Secretory Phenotype or SASP. Unfortunately, while SASP has its purpose, it also results in inflammation and tissue dysfunction[1].

Senescence can affect many different tissue types including connective tissue like tendons and muscles. Tendons are what attaches bone to muscle. Tendon maintenance is dependent on tendon stem and progenitor cells (TSPCs). As they age, these cells undergo a decrease in their ability to self-renew, differentiate, and migrate to their proper location[2].

Researchers investigated how senescence might be controlled in TSPCs. One suspected cause is changes in the number of aquaporins. Aquaporins are membrane protein channels that transport water in and out of the cell. There is some evidence that aquaporin activity might have an effect on aging. For example, we know that aged skin has less aquaporins than young skin. Some researchers also hypothesize that aquaporins can regulate stem cells. A decrease in one type of aquaporin, AQPI, for example, is associated with senescence of TSPCs[2]. 

To look at the affects of decreased AQPI directly, researchers analyzed old and young rat TSPCs. They observed a decrease in AQPI (expression) and JAK/STAT signalling in old rat TSPCs compared to young. JAK/STAT signalling is a complicated pathway in which multiple protein players act on each other. So, I won’t go into detail on that right now. Just remember 

that JAK/STAT controls gene expression[2].

These observations only make the clear that there is a correlation between old age and decreased AQPI and JAK/STAT signalling. So far, no causation is implied here yet. However,  researchers then increased the expression of AQP1 in rats. They then saw an increase in differentiation capacity, self-renewal, and migration in TSPCs. Essentially, the senescence phenotype of the TSPCs was restored to a more healthy and normal phenotype. Pretty cool. 

 So it looks like AQP1 plays a role in regulating TSPCs senescence[2]. But what do we do about this? Is messing with aquaporins to restore senescent cells a good therapy route?

We should acknowledge that this study is only one paper, and that parsing out cause and effect on a molecular scale is extremely hard (other factors could be involved: molecular pathways are complicated). Also, this was only done in mice. Additionally, a little common (biological) sense is needed: Even though increased stem cell function might seem beneficial, we should be careful. 

Always look at the restoration of senescence cells with a critical eye. Senescence is not just the result of wear and tear with no biological purpose in the body.  Yes, in aging, it is harmful. However, acutely, senescence plays an important role in preventing cancer. When a cell’s DNA gets damaged it has the choice of becoming senescent rather than replicating out of control into a tumor. This means we need to be wary of any therapy where we seek to block senescence. This is especially the case when we are already studying means to remove cells that have have become senescent with senolytics.

Source

1. AQP1 and Cellular Senescence in the Aging of Tendons. (2020, March 28). Retrieved September 04, 2020, from https://www.fightaging.org/archives/2020/04/aqp1-and-cellular-senescence-in-the-aging-of-tendons/

2. Chen, M., Li, Y., Xiao, L., Dai, G., Lu, P., Wang, Y., & Rui, Y. (2020). AQP1 modulates tendon stem/progenitor cells senescence during tendon aging. Cell Death & Disease, 11(3). doi:10.1038/s41419-020-2386-3