Progressive Hyperphosphorylation of Neurofilament Heavy Subunits with Aging: Possible Involvement in the Mechanism of Neurofilament Accumulation

Abnormal accumulations of phosphorylated neurofilaments occur both in normal senescence and in age-associated neurodegenerative diseases. In the present work, we study the physicochemical properties of neurofilaments isolated from rats of controlled ages. Aging induces in vivo hyperphosphorylation of the heavy neurofilament subunit without affecting in vitro neurofilament phosphorylation by the neurofilament-associated protein kinase. Interactions in vitro between neurofilaments from very old rats occur at higher rate and extent than that of neurofilaments from younger animals. These results support the hypothesis that the abnormal accumulation of neurofilaments observed in nervous tissues from aging mammals results from an altered equilibrium in situ between interconnected and independent neurofilaments.