The plasticity of fibroblasts: A forgotten player in the aging process

Tissue-resident fibroblasts are mesenchymal cells which possess an impressive plasticity in their ability to modify their properties according to the requirements of the microenvironment. There are diverse subgroups of fibroblast phenotypes associated with different tissue pathological conditions, e.g., cancers, wound healing, and many fibrotic and inflammatory conditions. The heterogeneous phenotypes can be subdivided into fibrogenic and nonfibrogenic, inflammatory and immunosuppressive subtypes as well as cellular senescent subsets. A major hallmark of activated fibroblasts is that they contain different amounts of stress fibers combined with & alpha;-smooth muscle actin (& alpha;-SMA) protein, i.e., commonly this phenotype has been called the myofibroblast. Interestingly, several stresses associated with the aging process are potent inducers of myofibroblast differentiation, e.g., oxidative and endoplasmic reticulum stresses, extracellular matrix (ECM) disorders, inflammatory mediators, and telomere shortening. Accordingly, anti-aging treatments with metformin and rapamycin inhibited the differentiation of myofibroblasts in tissues. There is evidence that the senescent phenotype induced in cultured fibroblasts does not represent the phenotype of fibroblasts in aged tissues. Considering the versatile plasticity of fibroblasts as well as their frequency and structural importance in tissues, it does seem that fibroblasts are overlooked players in the aging process.

Automated summary

Tissue-resident fibroblasts possess plasticity and can modify their properties according to the microenvironment. Different phenotypes of fibroblasts are associated with various tissue pathological conditions, and they can be subdivided into fibrogenic, nonfibrogenic, inflammatory, immunosuppressive, and senescent subsets. The differentiation of myofibroblasts, a major activated fibroblast phenotype, can be induced by multiple stresses associated with aging, and anti-aging treatments can inhibit this differentiation. The versatile plasticity and structural importance of fibroblasts suggest that they play a significant role in the aging process.