Fibroblasts in Old Skin Lose their Functional Identity

Researchers here describe the character of fibroblasts in old skin as a loss of characteristic function and identity. The fibroblasts begin to take on aspects of other cell types, and thus the character of skin changes for the worse. In the publicity materials this decline in cell function is described as a cause of aging, but that should probably be taken to mean that the researchers consider it a contributing cause to age-related pathology rather than a root cause of aging per se. Dysfunction of this nature has all the signs of being a downstream consequence in aging, cellular misbehavior that is a reaction to earlier processes, such as the accumulation of molecular damage within and between cells, or the changes in cell signaling that results from that damage.

With age, our tissues lose their function and capacity to regenerate after being damaged. The main conclusion drawn from recent findings is that these fibroblasts lose their cell identity, as if they had "forgotten" what they are, and consequently their activity is altered, thus affecting tissue. The new study reveals the cellular and molecular pathways affected by ageing and proposes that they could be manipulated to delay or even reverse the skin ageing process.

Dermal fibroblasts are key for the production of collagen and other proteins that make up the dermis and that preserve the skin's function as a barrier. The activity of these cells is also crucial for the repair of skin damage. As we age, the dermis loses its capacity to produce collagen, and consequently its capacity to repair wounds is also significantly impaired. A single-cell analysis confirmed the loss of fibroblast identity in aged animals. Using sophisticated computational tools, scientists observed that aged fibroblasts show a less defined molecular conformation compared to young fibroblasts and come to resemble the undefined cell states observed in newborn animals.

"The elderly face many problems in this regard because their skin does not heal properly and its barrier properties are decreased, thus increasing the risk of skin infections and systemic infections. The notion that the loss of cell identity is one of the underlying causes of ageing is interesting and one that we believe hasn't been considered before."