Innate immunity and inflammation are a major component of senescence and aging-associated pathology. Successful aging or aging with disease has been suggested to depend largely upon a complex balance between”inflammaging” and “anti-inflammaging”. The innate immune system includes a cellular and a humoral arm. PTX3, originally identified by the Coordinator (cloning of the mouse and human cDNA and genomic) is a fluid phase pattern recognition molecule (PRM) which has served as a paradigm for humoral innate immunity, linking cellular and humoral effectors and having a regulatory function. The general objective of this proposal is to investigate the role of PTX3, as a paradigmatic regulatory component of humoral innate immunity, in resistance to aging relevant pathogens (i.e. Streptococcus pneumoniae) and in the orchestration of tissue repair and obesity key processes relevant to aging related to inflammation. In addition, PTX3, including genetic and epigenetic regulation, will be investigated in successful aging and longevity. This proposal will take advantage of unique tools developed by, or available to, the applicants, including human samples. The efforts proposed here are expected to provide new vistas on the orchestration of innate immunity and inflammation in homeostasis and defence in aging as well as new tools for translation.
