Researchers provide novel insights into human skin aging

Photo by Jorge Royan

Researchers at the Institute of Zoology and the Beijing Institute of Genomics of the Chinese Academy of Sciences collaborated on a study to establish the first single-cell transcriptomic atlas of human skin aging. Using the single-cell transcriptome sequencing technology, researchers produced a comprehensive roadmap of the aging of human skin at the single-cell resolution and identified the disturbance of growth-controlling transcription factors as a major feature of human skin aging.

The study was published online ahead of print in the journal Developmental Cell (Nov. 24, 2020).

For their research, the study’s authors obtained eyelid skin samples from a group of healthy female donors of different ages. Morphological analysis revealed that epidermal thickness, the convolution of dermal-epidermal junction and dermal collagen density were decreased during aging.

Through the single-cell transcriptome sequencing analysis, the study’s authors identified 11 skin cell types with unique gene expression signatures and classified human epidermal basal cells into six subpopulations of quiescent or amplifying epidermal basal cells based on their transcriptional identities by hierarchical differentiation. Researchers conducted an in-depth dissection of the changes of gene expression during human skin aging which revealed that the skin of middle-aged individuals was transcriptionally more similar to the skin of elderly individuals than to the skin of young individuals, indicating that age-related gene expression changes start to accumulate early in life.

“Compared with younger individuals, the skin of elderly individuals exhibited increased inflammation and decreased epithelial maintenance ability,” the study’s authors wrote. “As the eyelid skin was exposed to daily sunlight, further analysis revealed age-related decrease in DNA repair capacity and increase in biomacromolecular damage in several types of skin cells, suggesting that chronic inflammation and photodamage may be important triggers of ocular skin aging.”

Additionally, the investigators observed early-onset downregulation of growth-controlling transcription factors (HES1 in fibroblasts and KLF6 in basal cells) underlying the cell type-specific transcriptional changes. The researchers found inactivation of HES1 in human dermal fibroblasts or KLF6 in human keratinocytes led to cellular senescence.

Further, the activation of HES1 alleviated the senescence of dermal fibroblasts, indicating that HES1 may exert protective effects on the skin.

Finally, the study’s authors found that a natural compound quercetin attenuated the senescence of dermal fibroblasts, providing a new potential intervention strategy for interfering human skin aging.

“This study provides an in-depth understanding of the cell type-specific mechanisms of human skin aging at the single-cell level and thus facilitates the development of novel therapeutic strategies combating aging-related skin diseases,” the study’s authors wrote.