New compounds created to penetrate and protect against damaging UV radiation

August 11, 2021
New compounds created to penetrate and protect against damaging UV radiation

An international research team has studied and invented a new way to protect the deeper layers of skin from harmful ultraviolet (UV) radiation from the sun. More precisely, a team from the University of Exeter Medical School, UK, and the Faculty of Medicine Siriraj Hospital, Mahidol University, in Thailand, have found how UVA – the part of natural sunlight which damages unprotected skin and can penetrate through windows, and even through some clothes – causes skin to age prematurely by turning on skin digesting enzymes called collagenases. Collagenases eat away at the natural collagen in the skin, causing it to lose elasticity and sag, resulting in wrinkles.

While typical sun creams people use sit on top of the skin and protect against sunburn from certain UV radiation (UVB), they do not penetrate the skin where the long-lasting damage occurs. But UVA does penetrate deeper into skin than UVB and damages cellular DNA, leading to mutations that can contribute to some skin cancers.

Read also: Warning for users of sun protection

Recently, two compounds invented at the University of Exeter, AP39 and AP123, have been shown to work more than existing sun creams. The compounds did not protect the skin in the same way to prevent sunburn, but instead penetrated the skin to correct how skin cells’ energy production and usage was turned off by UVA exposure. This then prevented the activation of collagenase enzymes and subsequent skin damage.

Professor Uraiwan Panich, of the Faculty of Medicine Siriraj Hospital, Mahidol University, said: “The compounds AP39 and AP123 specifically target the energy-generating machinery inside our cells, the mitochondria, and supply them with minute quantities of alternative fuel, hydrogen sulfide, to use when skin cells are stressed by UVA. The direct result of this was the activation of two protective mechanisms: one is a protein call PGC-1α, which controls mitochondria number inside cells and regulates energy balance; the other is Nrf2, which turns on a set of protective genes that mitigate UVA damage to skin and turn off the production of collagenase, the main enzyme that breaks down collagen in damaged skin tissue and causes skin to look significantly more “aged”.”

From the experiments, the compounds were seen to only regulate energy production of PGC-1α and Nrf2 in skin that was exposed to UVA. In an anti-ageing context, they prevented human skin cells in test tube experiments from ageing, but this is the first time the effects of photo-ageing are apparent in mice – the compounds are a novel approach to treating skin that has already been damaged by UV radiation, and could potentially reverse, as well as limit, that damage.

The compounds used in this study have also been shown to have impressive effects in reducing skin inflammation and skin damage after burn injury and atopic dermatitis (eczema).

Professor Matt Whiteman, of the University of Exeter Medical School, added: “Some skin sun creams and cosmetics contain ingredients thought to protect mitochondria from UV radiation. However, it isn’t clear that these cosmetic skin-applied substances get inside skin cells at all, whereas we found that our molecules penetrate cells and specifically target mitochondria where they are needed. By protecting mitochondria, we also preserve and upregulate the protective mechanisms by which mitochondria control inflammation, protect cells and prevent tissue destruction.

“Currently, we have no way of reversing or delaying skin ageing caused by sunlight exposure. Our results are a really exciting step towards that goal, and could one day help reduce age-related skin conditions, as well as be useful in other conditions resulting from the ageing process.”

The Exeter team are currently mid-way through testing newer and more potent molecules able to do the same task through the University of Exeter spin-out company MitoRx Therapeutics; a company developing highly potent mitochondrial drugs for clinical use.

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Category: Features, Top Story

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