Resumen de Hallmarks of dermal fibroblast aging
Aging is accompanied by cellular, extracellular and systemic changes that impair tissue function. Stromal alterations, such as degeneration of the extracellular matrix, are thought to contribute to organ deterioration in the elderly, yet little is known whether this is caused by changes in fibroblasts, the main cellular component of stroma. Using population- and single-cell whole transcriptomics, as well as long-term lineage tracing, we studied if and how murine dermal fibroblasts are altered during physiological aging. Old dermal fibroblasts not only reduce the expression of genes involved in the formation of the extracellular matrix but, intriguingly, also gain adipogenic traits. Many of these age-related alterations are influenced by systemic changes in metabolism: long-term caloric restriction prevents them in old fibroblasts in a reversible manner, whereas a high-fat diet potentiates them in young fibroblasts. Single-cell RNA sequencing detects two fibroblast subtypes in adult dermis: one characterized by expression of collagens, and the other characterized by expression of genes involved in processes of oxidation-reduction and immune regulation. We show that the identity of these two populations becomes blurred with age, and that gene expression of old fibroblasts is noisy. Our results therefore highlight that identity-noise and the acquisition of adipogenic traits are mechanisms that accompany fibroblast aging, which is sensitive to changes in systemic metabolism.
