This Program Project is founded on the premise that AGING is a natural process and that many changes occur as an extension of normal development. We propose to test this thesis by chemically characterizing the PROTEOGLYCANS synthesized by non-cartilage tissue as a function of age, starting with very early development through adulthood and in aged subjects. We base this exploration on our considerable experience in the characterization of cartilage proteoglycans where in chick embryonic cartilage, bovine and sheep cartilages and human cartilages we and others have been able to show that there is an age-dependent programmatically controlled changing pattern of proteoglycan biosynthesis. The individual projects described here use chick muscle, aging human fibroblast cell lines and primary isolates of skin fibroblasts from human subjects scored for genetic history, chronological age and """"""""apparent skin age"""""""" as sources for proteoglycans. Detailed chemical, physical chemical and electron microscopic analyses of purified proteoglycans during early development, adulthood and senescent stages will be conducted. We intend to focus on the proteoglycans in the extracellular matrix both closely associated with the cells (surface adhesion material) and in the space between cells. By analyzing the newly synthesized material we hope to be able to describe the programmatically controlled biosynthesis of proteoglycans as well as gain insight into various organizational and interactive properties of these complex macromolecules. A goal of these descriptive explorations is to attempt to relate the chemical and physical chemical properties of proteoglycans with age-related changes of the tissues from which the cells originated. Such a detailed characterization of proteoglycan biosynthesis, structure and function should allow us to comment on the validity of the thesis of the """"""""the ontogenetic basis of aging.""""""""
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