IL-17 protein identified as playing central role in skin ageing

Wrinkles are a natural part of ageing. But few of us welcome their appearance.

Whilst we may be prepared to embrace the wisdom and experience that comes with age, the same can’t be said of those telltale lines, creases, furrows and folds that so visibly announce to the world that our salad days are behind us.

Such is our horror at quite literally being faced with a face full of crow’s feet and worry lines, that a multi-billion dollar industry has grown up pandering to our frantic attempts to turn back time.

The global anti-ageing market is estimated to be worth more than $60bn US dollars. As society becomes increasingly more beauty-conscious, the market for anti-ageing and skin-changing products is projected to reach a staggering $93bn by 2027.

But a new study conducted by a team of scientists from the Institute for Research in Biomedicine (IRB) and the National Center for Genomic Analysis (CNAG), both in Barcelona, has now identified the protein that plays a key role in skin ageing – opening up the possibility of new therapies being developed targeted at improving skin health.

The study published in the journal Nature Aging and led by Dr Guiomar Solanas and Dr Salvador Aznar Benitah, both of IRB Barcelona, and Dr Holger Heyn at CNAG, reveals that blocking the function of IL-17 delays the appearance of age-related features in the skin.

Skin ageing is characterised by a series of structural and functional changes that gradually contribute to the deterioration and fragility associated with age. Aged skin has a reduced capacity to regenerate, poor healing ability, and diminished barrier function.

Dr Benitah, who is head of the Stem Cells and Cancer laboratory at IRB Barcelona, said: “Our results show that IL-17 is involved in various functions related to ageing. We have observed that blocking the function of this protein slows down the appearance of various deficiencies associated with ageing skin.

“This discovery opens up new possibilities for treating some of the symptoms or facilitating skin recovery after surgery, for example.”

Dr Heyn, head of the Single Cell Genomics laboratory at CNAG, added: “Single cell sequencing has allowed us to dive deep into the complexity of cell types and states forming the skin and how these change during lifespan.

“We did not only find differences in the composition of aged skin, but also changes in cell activity states. Particularly immune cells showed specific age-related profiles, which we could pinpoint by analysing thousands of individual cells one at a time.”

In addition to a wide variety of epithelial cells, hair follicle cells, and other components, the skin is also home to immune cells, which play a crucial role in preventing infection and protecting against different damages.

The groundbreaking researh describes how, during ageing, the presence of some of these immune cells, namely gamma delta T cells, innate lymphoid cells, and CD4+ T cells, significantly increases in the skin. These same cells also start expressing very high levels of the pro-inflammatory cytokine IL-17.

Dr Paloma Solá, first author of the paper, together with Dr Elisabetta Mereu, who is now a researcher at the Josep Carreras Leukaemia Research Institute in Barcelona, said: “Ageing is associated with mild but persistent inflammation and, in the skin, this is characterised by a significant increase in IL-17, which causes skin deterioration.”

Previous studies had described that IL-17 is related to some autoimmune skin diseases, such as psoriasis, and there are existing treatments that block this protein.

The team of researchers studied the response of various aspects to blocking IL-17 activity, including hair follicle growth, transepidermal water loss, wound healing, and genetic markers of ageing.

These four parameters showed an improvement after treatment, as the acquisition of these ageing traits was significantly delayed.

Dr Solanas, associate researcher at IRB Barcelona, commented: “IL-17 protein is essential for vital body functions, such as defence against microbes and wound healing, so permanently blocking it would not be an option. What we have observed is that its temporary inhibition offers benefits that could be of interest at a therapeutic level.”

Future work by the researchers will focus on clarifying the ageing processes that are related to inflammatory states in the skin and how these are linked to IL-17.

The team will also address whether IL-17 is involved in the ageing and deterioration of other tissues and organs.