The proposed NIH KL2 INCLUDE Career Development Award supports a promising dual-degree (DDS, PhD) early career faculty to train in the clinical and translational research to improve and extend the oral healthspan in people with Down syndrome (DS). With a higher prevalence of oral inflammatory diseases, like periodontitis and gingivitis, at an earlier age (<30 years old in people with DS vs. >65 years old in people without DS), the underlying impact of aging biology remains largely unexplored. Specifically, this proposal will investigate the role of low-grade, chronic inflammation, termed “inflammaging” in the periodontal barrier of children with DS. Further, this proposal will set up future work to address INCLUDE Project priorities, Component 1, by identifying a DS mouse model best suited to mimic accelerated human oral inflammation in addition to investigating mechanisms of inflammaging in the gingival barrier, and Component 2, by assessing the oral health landscape in people with DS using epidemiological inquiry. The KL2 scholar will leverage collaborations at clinical and dental sites that see over 600 children and adults with DS to complete the proposed work and engage with the DS community in Washington State. The KL2 scholar will be supported by the Institute of Translational Health Sciences (ITHS), the Clinical and Translational Science Award (CTSA) program hub at the University of Washington (UW), UW School of Dentistry, and mentored by established researchers to develop as an investigator conducting rigorous clinical and translational research. The mentoring team for the KL2 scholar is comprised of NIH-funded researchers (OD, NIAID, NHLBI, NCATS, NIDCR) who are experts in single-cell analysis, mucosal immunology, DS immunology and deep phenotyping, and epidemiology. Mentors will advance the scholar's career development by helping him to build trans-disciplinary collaborative relationships and train in novel research activities. Importantly, this award will provide the applicant with the protected time, resources, salary support, and training and development to take his career to the next level in establishing an independent clinical and translational research career in DS-related research, specifically to extend the oral healthspan in children and adults with DS.