Can Lipofuscin Be Made Less Harmful?
Lipofuscin is a mix of metabolic byproducts that the body cannot break down. It accumulates with age, and causes some important forms of cellular dysfunction that contribute to aging. Ideally researchers would be working on ways to periodically clear liposfuscin from the body, but here they are investigating how it might be made less damaging: "Lipofuscin, a highly oxidized aggregate consists of covalently cross-linked proteins, lipids and sugar-residues, and is one of the major lifespan-limiting factors in postmitotic aging cells. An artificial model of this material, showing characteristics and effects comparable to the natural form, has turned out to be very useful for in vitro studies. Artificial lipofuscin was used to investigate its effects on the viability of human fibroblasts, its rate of uptake and its ability to inhibit the proteasomal system. The inhibition of the proteasomal system is one of the major aspects of the cytotoxic effects of lipofuscin. We present here that this proteasomal inhibition is due to a proteasomal binding on the lipofuscin surface motifs, degradable by protease K. Furthermore, removal of surface peptide structures by protease K strongly reduces cytotoxic effects of lipofuscin and binding of cellular proteins and proteasome to intracellular protein aggregates." Achieving this end would still leave the lipofuscin stuck in the cell, bloating the lysosomes, however - breaking it down would be much better.