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Cell. 2018 Nov 29;175(6):1575-1590.e22. doi: 10.1016/j.cell.2018.10.012. Epub 2018 Nov 8.

Identity Noise and Adipogenic Traits Characterize Dermal Fibroblast Aging.

Author information

1
Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.
2
CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.
3
Director of PCB-PRBB Animal Facility Alliance.
4
CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain. Electronic address: holger.heyn@cnag.crg.eu.
5
Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain; Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain. Electronic address: salvador.aznar-benitah@irbbarcelona.org.

Abstract

During aging, stromal functions are thought to be impaired, but little is known whether this stems from changes of fibroblasts. Using population- and single-cell transcriptomics, as well as long-term lineage tracing, we studied whether murine dermal fibroblasts are altered during physiological aging under different dietary regimes that affect longevity. We show that the identity of old fibroblasts becomes undefined, with the fibroblast states present in young skin no longer clearly demarcated. In addition, old fibroblasts not only reduce the expression of genes involved in the formation of the extracellular matrix, but also gain adipogenic traits, paradoxically becoming more similar to neonatal pro-adipogenic fibroblasts. These alterations are sensitive to systemic metabolic changes: long-term caloric restriction reversibly prevents them, whereas a high-fat diet potentiates them. Our results therefore highlight loss of cell identity and the acquisition of adipogenic traits as a mechanism underlying cellular aging, which is influenced by systemic metabolism.

KEYWORDS:

adipogenesis; aging; caloric restriction; cell fate; dermis; epidermis; fibroblasts; high-fat diet; single-cell RNA-sequencing; stem cells

PMID:
30415840
DOI:
10.1016/j.cell.2018.10.012

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