Longevity Briefs: Could We Reverse Hair Loss By Targeting ‘Zombie Cells’?

Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.

The problem:

Scientists have attempted to reverse age-related hair loss using dermal papilla cells – stem cells that reside at the base of the hair follicle. These cells can develop into other cell types and are essential for maintaining the cycle of hair growth. The problem is that when these cells are removed from the hair follicle and cultured in a dish, they quickly lose their ability to promote hair growth. This is at least partly due to a process called cellular senescence. 

After cells have divided a certain number of times or have been badly damaged, they enter a state called senescence. These ‘zombie cells’ refuse to die but are also unable to divide or function correctly. Worse, they release signals that turn nearby cells senescent. Cellular senescence is thought to be a major driver of ageing, but there are some drugs (called senolytics) that will clear senescent cells. In this study, researchers investigate whether this strategy can help prevent dermal papilla cells from losing their hair-growing properties.

The discovery:

The researchers first isolated and cultured human dermal papilla cells and dermal fibroblasts (closely related cells that don’t contribute to hair growth) from the scalp of the same donor. By looking at a well known marker of senescence called beta galactosidase, they confirmed that the dermal papilla cells became senescent at a much higher rate than the dermal fibroblasts. They also detected an increase in inflammatory molecules responsible for spreading senescence to neighbouring cells.

The researchers then tested various combinations of senolytic drugs and found that the well studied senolytic combination of dasatinib and quercetin (D+Q) was most effective, resulting in the removal of most senescent dermal papilla cells after 48 hours. Dasatinib is an approved cancer-targeting drug, while quercetin is a plant antioxidant and anti-inflammatory molecule. When the researchers then cultured dermal papilla cells and injected them into the skin of hairless mice or into collagen, they found that cells treated with D+Q were more effective at inducing hair growth. That said, cells that had undergone fewer divisions prior to treatment with D+Q were still more effective, suggesting that hair-growing potential decreased over time even in the non-senescent cells.

The implications:

While this study doesn’t provide us with a new treatment for hair loss, it may bring us one step closer. Senolytics are a promising drug class for treating a variety of age-related conditions, as senescent cells are implicated in most age-related diseases. Unfortunately, there is currently little evidence for the effectiveness of senolytics in humans. There are also some challenges associated with their use, such as the fact that senescence is actually necessary for certain processes, like wound healing. These concerns aren’t really a problem when using senolytics on cultured cells, since only these cells are being introduced into the skin and not the senolytic drugs themselves.