Skin nerve endings send collagen-producing cells a signal that restrains their aging

Skin nerve endings send collagen-producing cells a signal that restrains their aging

On July 17, Cell published a study on the relationship between nerve endings and skin condition. In a study of 148 people, the authors observed age-related declines in Nefh and collagen. They then tested the causal pathway in skin models. The pathway involves glutamate, a chemical signal that nerve cells use to communicate with neighboring cells.

Fibroblasts produce collagen, which keeps tissue firm and elastic. With age, they enter senescence, meaning that they stop dividing normally and alter their surrounding environment. The new study examines how signals from nerve fibers affect fibroblasts in a skin model.

The authors add nerve endings to this picture. Fibroblasts were often in contact with nerve fibers carrying Nefh. This protein was found mainly in neurons that release glutamate. Nefh is the neurofilament heavy chain, a protein that supports the structural framework of nerve cells.

Loss of Nefh altered fibroblast state through a neuronal signal. When the researchers removed Nefh from glutamate-releasing neurons in skin models, fibroblasts entered a senescent state more often, and the skin lost collagen. Skin denervation produced a similar effect: markers of aging increased as collagen was lost.

The authors then examined the pathway in detail. Cdk5 interacts with both Nefh and Vglut2, the transporter that loads glutamate into vesicles for release from neurons. In fibroblasts, the effects of glutamate depended on Slc1a3, a transporter protein. In the models, adding glutamate reduced markers of senescence and supported collagen production.

In skin models, disrupting the signal from a neighboring nerve altered fibroblast state and collagen content. Research on skin aging can now test how to preserve communication between nerve endings and the tissue they serve.

In human samples, the study shows an association with age, while Nefh removal and glutamate supplementation were tested in skin models. Therapeutic use will require separate evidence on signal delivery, safety, and the duration of the effect. In the models, loss of Nefh in glutamate-releasing neurons reduced this signal, increased fibroblast senescence, and lowered collagen content.