Growth differentiation factor 11 (GDF11), a secreted member of the TGF-β superfamily, has recently been suggested as an anti-aging factor that declines with age in the bloodstream, and restoration of the youthful level by administration of its recombinant protein could reverse age-related dysfunctions. However, its effects on titanium implant osseointegration and mandibular bone during aging remain unknown.Two-month-old and 18-month-old C57BL male mice were given daily intraperitoneal injections of recombinant GDF11 (rGDF11) or vehicle for 6 weeks. Experimental titanium implants were inserted into femurs on the 4 week. Inhibition of GDF11 function was achieved by GDF11 antibody. Implant-bearing femurs were subjected to histomorphometric analysis and biomechanical evaluation. Mandibles were scanned with micro-CT and decalcified for histological measurements.In both young adult and aged mice, supraphysiologic GDF11 leads to a significantly decreased bone-implant-contact ratio (BIC) and peri-implant bone volume (BV/TV) at the histologic level and reduced resistance at the biomechanical level, indicating weakened implant fixation. Moreover, rGDF11 administration resulted in less trabecular bone volume and thinner cortical thickness in the mandible, which was further compromised in the old animals. In contrast, inhibition of GDF11 improved peri-implant bone healing in old mice.Rather than functioning as a rejuvenating factor, exogenous GDF11 negatively affects not only titanium implant healing but also mandibular bone in both young and old mice. In contrast, neutralization of endogenous GDF11 has positive effects on implant fixation in aged mice. Therefore, treatment aimed at elevating GDF11 activity should be cautiously reconsidered. This article is protected by copyright. All rights reserved.