Dynamic Scaling of Lipofuscin Deposition in Aging Cells

Abstract

Lipofuscin is a membrane-bound cellular waste that can be neither degraded nor ejected from the cell but can only be diluted through cell division and subsequent growth. The fate of postmitotic (non-dividing) cells such as neurons, cardiac myocytes, skeletal muscle fibers, and retinal pigment epithelial cells (RPE) is to accumulate lipofuscin, which as an “aging pigment” has been considered a reliable biomarker for the age of cells. Environmental stress can accelerate the accumulation of lipofuscin. For example, accumulation in brain cells appears to be an important issue connected with heavy consumption of alcohol. Lipofuscin is made of free-radical-damaged protein and fat, whose abnormal accumulation is related to a range of disorders including Type IV mucolipidosis (ML4), Amyotrophic Lateral Sclerosis (ALS), Alzheimer’s disease, Parkinson disease, and age-related macular degeneration (AMD) which is the leading cause of blindness beyond the age of 50 years. The study of lipofuscin formation and growth is important, because of their association with cellular aging. We introduce a model of non-equilibrium cluster growth and aggregation that we have developed for studying the formation and growth of lipofuscin. As an example of lipofuscin deposit in a given kind of postmitotic cell, we study the kinetics of lipofuscin growth in a RPE cell. Our results agree with a linear growth of the number of lipofuscin granules with age. We apply the dynamic scaling approach to our model and find excellent data collapse for the cluster size distribution. An unusual feature of our model is that while small particles are removed from the cell the larger ones become fixed and grow by aggregation.