Depletion of growth differentiation factor 15 (<scp>GDF15</scp>) leads to mitochondrial dysfunction and premature senescence in human dermal fibroblasts
Sophia Wedel, Ines Martic, Lena Guerrero‐Navarro, Christian Ploner, Gerhard Pierer, Pidder Jansen‐Dürr, Maria Cavinato
Abstract
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.