Previous studies in our laboratory have shown the increased presence of altered enzyme molecules detected by antibody as cross reacting material (CRM) in aged nematodes and mice. It will be determined whether the synthesis and/or accumulation of faulty proteins in aging organisms is a universal phenomenon. Antibodies to purified mouse liver ornithine decarboxylase, nematode choline acetylase and ribosomal proteins will be used to screen for the presence of CRM in aged organisms. The mechanism(s) by which faulty proteins are produced will be studied by isolation of the CRM of mouse liver and muscle aldolases from the active enzyme. Peptide fingerprinting, amino acid and chemical analysis of the CRM will be performed and compared to intact enzyme of young animals. To date CRM has been detected by us in aged nematode isocitrate lyase and FDP aldolase and aged mouse muscle and liver aldolases. It is therefore imperative to determine whether the levels of CRM detectable at the terminal stages of life span are of primary significance in senescence and death. This shall be performed by simulating the senescent levels of CRM in young nematodes (T. aceti) by exposing them to the amino acid analogs ethionine and parafluorophenylalanine and the nucleotide base analogs 8-azaguanine and 5-fluorouridine. The levels of CRM produced by such fault inducing analogs will be monitored with all the above mentioned antibodies to nematode proteins. It will be determined whether the levels of CRM observed in naturally senescent T. aceti are sufficient to cause death in chronologically young animals carrying a senescent load of CRM.