Metabolic signaling in aging and disease

Abstract

The rate of biosynthesis and turnover of plasma protein fibrinogen is a marker of metabolic signaling in aging and disease. The rate in the young normal human subject of 0.260 mg/ml/24 hours increases to 0.378 in older normal subjects and to 0.466 in age matched coronary thrombosis patients measured by endogenous labeling of fibrinogen with L‐glutamic acid‐C14. This increased rate of fibrinogen turnover was traced to generation of occlusive fibrin polymers labeled by glycine‐C14 ethyl esters in the presence of active fibrin stabilizing factor. Circulating fibrin increased 520% (P<0.001) above normal in ischemic thrombotic cerebrovascular disease. Long chain saturated free fatty acids (FFA) exert not only primary control over incorporation of C14 amino acids into the fibrinogen structure but also activate the cascade sequence of reactions which convert fibrinogen into occlusive fibrin. FFA are normally transported by albumin to sites of energy metabolism. Decline in albumin synthesis in aging causes an increase in unbound FFA which induce not only increased fibrinogen synthesis but also activation of Hageman Factor generation of thrombin conversion of fibrinogen into occlusive fibrin. It has now been discovered that induction of a normal FFA/albumin ratio in plasma of coronary thrombosis and thrombotic stroke patients regenerates a normal level of fibrinogen synthesis by human hepatocytes.