Hair loss and greying, which are frequently dismissed as cosmetic issues, may be among the first obvious symptoms of human ageing, according to new research that maps how the scalp changes at the cellular level long before old age sets in. 

In a study headed by Dr Zhao and colleagues, scientists evaluated 11 human scalp samples using single-cell RNA sequencing, a technology that evaluates ageing cell by cell, as well as spatial transcriptomics, which shows where those cells are located within the skin. The study gives the first high-resolution, cell-by-cell map of how the human scalp ages during middle life. 

The researchers discovered that ageing is caused by the gradual failure of hair follicle stem cells and the supportive environment in which they exist, rather than by a single cause. These stem cells function as a repair crew for hair growth and colour. Hair thins, grows slowly, and loses pigment as it ages. 

Keratinocytes, the primary building blocks of skin and hair follicles, were discovered in a transitional stage across several scalp locations. These cells ordinarily generate keratin, which strengthens hair and protects the skin. As they age, their capacity to mature and function properly begins to deteriorate. 

Changes were also observed in fibroblasts, the skin's structural cells that govern the hair cycle and repair damage. The study found significant discrepancies between important fibroblast types—dermal papilla and dermal sheath cells—indicating that human hair ageing does not entirely replicate what is seen in animal models. 

Crucially, the study discovered a decrease in critical progenitor cells, particularly in the hair follicle bulge and outer root sheath, by middle age. At the same time, genes involved in cellular senescence (cells that stop proliferating), inflammation, and programmed cell death became increasingly active in various cell types. 

One of the most startling results was a breakdown in communication between cells responsible for hair growth. Signalling pathways such as BMP and non-canonical WNT—essential molecular "messages" that inform hair whether to grow or rest—were dramatically diminished. At the same time, researchers further noted that keratinocytes showed increased activity of AP-1, a stress-related genetic switch that is known to cause inflammation and age-related alterations. 

The study also found a correlation between ageing and pigment alteration. Increased DCT gene activity in melanocytes, the cells that determine the skin colour, indicates that chronic low-grade inflammation, called "inflammaging", may facilitate erratic melanin synthesis, thereby contributing to greying. 

The researchers say that the results fill a big gap in geroscience by showing how ageing shows up in visible tissues. They stress that additional study is needed to find the cause and make treatments, even if probable therapeutic targets have been found.