Characterization of Circulating Pro- and Anti-Geronic Proteins and Peptides (R01)

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The goal of this FOA is to advance research on the underlying basis for the transfer (or transposition) of aging phenotypes observed between young and old rodents and discovered through heterochronic parabiosis. Examples of transposed phenotypes include reversal of cardiac hypertrophy, partial restoration of cognitive function, improved vascularization, and repair of skeletal muscle after cryo-injury (anti-geronic transposition), or as accelerated loss of cognitive function and neurogenesis (pro-geronic transposition). Other transposed phenotypes, as revealed solely through heterochronic parabiosis, may also be reported in the literature. There are also reports of candidate factors found in circulation that might be causally related to the transposition of these aging phenotypes; these are termed "circulating geronic factors" for purposes of this FOA. To date, these are proteins and peptides that pass between the young and old mice joined by parabiosis, due to anastomosis of their circulatory systems. Based on these novel findings and this novel experimental paradigm, the specific objective of this FOA is to test whether these candidate geronic factors are necessary for the transposition of aging phenotypes. The focus is on phenotypes transposed in heterochronic parabiosis and the candidate factors which are present and functional at physiological concentrations in circulation.

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