Longevity Briefs: Healthy Brain, Healthy Skin?

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:

Skin ageing is the most immediately noticeable aspect of the ageing process, with a huge industry around making the skin appear younger. However, skin ageing isn’t just cosmetic – as we age, our skin becomes more fragile and its ability to heal wounds diminishes significantly. This decline is linked to the accumulation of senescent cells (‘zombie’ cells that have stopped dividing but refuse to die). These senescent cells contribute to inflammation, impaired collagen production, and reduced blood supply, all hindering the healing process.

It is well known that mental states like chronic stress can have an effect on the skin. The mechanism involves a variety of processes including the release of stress hormones, suppression of the immune system, and possibly more direct routes. This has led to the theory that just as there is a brain-gut axis, in which the gut and the brain influence each other directly via hormones and the nervous system, it may also be helpful to think about a ‘brain-skin axis’. This raises the question of whether a healthy brain might promote healthy skin as well. In this study, researchers isolate factors released by the brains of young animals and investigate their effects on ageing skin.

The discovery:

Researchers first isolated youthful brain-derived extracellular vesicles (YBEVs) from young (4 week-old) rats. Extracellular vesicles (EVs) are microscopic membrane packages released by cells, and can deliver genetic material and signalling molecules to other cells over long distances. The researchers then took human dermal fibroblasts (HDFs), the predominant cells in the skin’s connective tissue, and exposed them to chemicals in order to induce senescence. They found that when these senescent cells were treated with YBEVs, markers of senescence were reduced, the cells’ collagen production improved, as did production of other proteins crucial for wound healing, and the ability of the cells to migrate was enhanced. They also observed that YBEVs improved the health of the mitochondria (the ‘power plants’ of the cell). Dysfunction of the mitochondria is thought to be a significant component of ageing.

To investigate whether this would translate to better wound healing, researchers took 5 rats that were 4 weeks old and 15 rats that were 20 months old (very roughly ‘equivalent’ to a 50 year-old human). They gave the rats skin wounds and then divided them into four groups: a young untreated group, an aged untreated control group, an aged group treated with YBEVs embedded in a hydrogel (designed to release the extracellular vesicles into the wound slowly over time), and an aged group treated with hydrogel alone as an additional control. After 14 days, the rats treated with YBEV hydrogel had significantly accelerated wound healing, matching the healing rate of young rats. They also had increased blood vessel formation, collagen deposition and even improved hair follicle regeneration compared to the control groups.

The implications:

This research suggests that EVs from the brain can restore impaired wound healing in aged skin, at least in rats, and could potentially have other benefits in ageing skin. But what exactly do these extracellular vesicles contain? According the analyses performed in this study, YBEVs contained numerous proteins associated with mitochondrial function and the Krebs cycle – the chemical reactions within the mitochondria that constitute a major step in the extraction of energy from nutrients. Mitochondrial function has knock-on effects on everything else that occurs within a cell, and poor mitochondrial function can contribute to senescence. Interestingly, while senescence is a component of ageing that contributes to poor wound healing, senescent cells actually contribute to wound healing in a beneficial way in healthy tissue, so their role is not so straightforward.

While this study hints at therapeutic potential for some kind of engineered EV, we don’t know to what extent they naturally contribute to skin health and healing in young organisms. It’s therefore too early to claim that maintaining a healthy brain would improve skin health through this mechanism, though it is an interesting prospect to consider.