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The senescent phenotype was assessed by analyzing cellular morphology, proliferative capacity, and senescence marker expression. Furthermore, GDF15 levels were measured and subsequently modulated by small interfering RNA(siRNA)-mediated knockdown and by ponsegromab, a\u00a0novel GDF15-neutralizing antibody. Tensile and compressive forces were applied using BioFlex\u00ae Culture Plates (FLEXCELL\u00ae, Dunn Labortechnik, Asbach, Germany) and sterile glass plates, respectively. The mechanoresponses of hPdLFs were characterized by analyzing pro-inflammatory cytokine levels and the activation of immune cells as well as of bone-remodeling osteoblasts and osteoclasts.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Aged hPdLFs exhibited decreased proliferation, increased \u03b2\u2011galactosidase activity, and morphological changes indicative of cellular senescence. Elevated baseline and force-induced intra- and extracellular GDF15 levels were observed in aged hPdLFs correlating with enhanced pro-inflammatory cytokine expression and immune cell activation. While aged hPdLFs showed reduced activation of osteoblasts in response to tensile forces, compressive forces led to increased osteoclast activation. Remarkably, modulating intra- and extracellular GDF15 levels partially restored the deregulated activation of bone-remodeling cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Aging altered the mechanobiological response of PdL fibroblasts by promoting a\u00a0hyperinflammatory microenvironment and shifting bone remodeling towards degenerative processes. Senescence-associated increases in GDF15 contributed to these changes by force-dependent intra- and extracellular signaling pathways. Targeting GDF15 could offer a\u00a0therapeutic potential to optimize bone remodeling and improve orthodontic care for the elderly.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00056-025-00600-2","type":"journal-article","created":{"date-parts":[[2025,7,16]],"date-time":"2025-07-16T07:40:20Z","timestamp":1752651620000},"page":"490-504","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["GDF15 modulates aging-associated adaptions in the mechanoresponse of periodontal ligament fibroblasts","GDF15 moduliert alterungsassoziierte Anpassungen in der Mechanoreaktion von parodontalen Ligamentfibroblasten"],"prefix":"10.1007","volume":"87","author":[{"given":"Judit","family":"Symmank","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Rieger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph-Ludwig","family":"Hennig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annika","family":"D\u00f6ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrike","family":"Schulze-Sp\u00e4te","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Collin","family":"Jacobs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,15]]},"reference":[{"key":"600_CR1","doi-asserted-by":"publisher","first-page":"1460168","DOI":"10.3389\/fphys.2024.1460168","volume":"15","author":"J Wang","year":"2024","unstructured":"Wang\u00a0J, Huang\u00a0Y, Chen\u00a0F, Li\u00a0W (2024) The age-related effects on orthodontic tooth movement and the surrounding periodontal environment. 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