Fighting Age-Associated Bone Loss in Periodontitis with Dietary Interventions

Aging is a systemic immunomodulatory condition that makes organisms more susceptible to infection-driven periodontitis and associated periodontal tissue loss. Therefore, modulation of the bacterial-induced inflammatory host response could potentially target the pathophysiological systemic and local crosstalk and resulting tissue homeostasis in aged organisms. However, underlying pathways connecting nutritional modulation with periodontal disease pathology and whether an aged organism benefits from specific immunomodulatory nutritional components are not known. Based on its potent immunomodulatory function, we determined whether nutritional interventions with dietary monounsaturated fatty acid (FA) oleic acid (OA [C18:1]), a main component of Mediterranean-style diets, as compared with a Western-style diet component saturated FA palmitic acid (PA [C16:0]) could modify the response to periodontal infection in a murine periodontal <i>Porphyromonas gingivalis</i>-inoculation model comparing old (final age of up to 2 y) and young (21 wk) mice. Local fibroblastic response and circulating regulatory immune-competent lipid mediators (LMs) were determined to provide insights into underlying pathways and how diet and age affect inflammation and resolution of the periodontal infection. The dietary intake of PA enhances periodontal bone destruction in response to <i>P. gingivalis</i> infection in old mice, whereas an OA-enriched diet (ED) has a protective effect. Specifically, PA-ED enhances the inflammatory profile of the periodontal microenvironment and primes gingival fibroblasts, prominent regulators within local tissue homeostasis, toward an inflammatory phenotype. Moreover, systems-wide serological lipidomic analyses of LMs and their respective stimulation of osteoclast differentiation revealed 10-hydroxydocosahexaenoic acid, associated with OA intake, as a protective candidate for age- and nutrition-dependent regulation of osteoclast-driven bone loss. Given the rising prevalence of periodontitis in the aging population, incorporating OA-rich foods could offer promising strategies for addressing the sequelae of aging and promoting periodontal health.