biostudies-literatureWedel SAustrian Science Fund FWFUniversity of InnsbruckUniversität InnsbruckEuropean CommissionEuropean Comission (COFUND-ARDRE)e13752https://www.ebi.ac.uk/biostudies/studies/S-EPMC9835581biostudies-literatureUnknown22(1)Growth differentiation factor 15 (GDF15) is a stress-responsive cytokine also known as a mitokine; however, its role in mitochondrial homeostasis and cellular senescence remained elusive. We show here that knocking down GDF15 expression in human dermal fibroblasts induced mitochondrial dysfunction and premature senescence, associated with a distinct senescence-associated secretory phenotype. Fibroblast-specific loss of GDF15 expression in a model of 3D reconstructed human skin induced epidermal thinning, a hallmark of skin aging. Our results suggest GDF15 to play a so far undisclosed role in mitochondrial homeostasis to delay both the onset of cellular senescence and the appearance of age-related changes in a 3D human skin model.Aging cellDepletion of growth differentiation factor 15 (GDF15) leads to mitochondrial dysfunction and premature senescence in human dermal fibroblasts.PMC9835581847681P 31582332930346577Pierer GJansen-Durr PGuerrero Navarro LWedel SMartic IPloner CCavinato MfalseDepletion of growth differentiation factor 15 (GDF15) leads to mitochondrial dysfunction and premature senescence in human dermal fibroblasts.Growth differentiation factor 15 (GDF15) is a stress-responsive cytokine also known as a mitokine; however, its role in mitochondrial homeostasis and cellular senescence remained elusive. We show here that knocking down GDF15 expression in human dermal fibroblasts induced mitochondrial dysfunction and premature senescence, associated with a distinct senescence-associated secretory phenotype. Fibroblast-specific loss of GDF15 expression in a model of 3D reconstructed human skin induced epidermal thinning, a hallmark of skin aging. Our results suggest GDF15 to play a so far undisclosed role in mitochondrial homeostasis to delay both the onset of cellular senescence and the appearance of age-related changes in a 3D human skin model.2023-01-01T00:00:00Z2023 Jan2025-04-05T12:04:21.597Z2025-04-05T12:04:21.597ZS-EPMC98355813654702110.1111/acel.13752